This article mainly introduced novel carrier-modified methods for active targeting antitumor preparation as well as their evaluation methodology in recent years. By reviewing related domestic and overseas literatures,...This article mainly introduced novel carrier-modified methods for active targeting antitumor preparation as well as their evaluation methodology in recent years. By reviewing related domestic and overseas literatures, the up-to-date scientific researches concerning active targeting antitumor preparation were elaborated and the problems existing in present studies were discussed. Numerous valid vector- embellished methods had been discovered with excellent targeting effects, and the significant progress was acquired for the evaluation tools in vitroand in vivo. The active targeting agent would be a major direction in prospective tumor or cancer therapeutic regimen.展开更多
The ^(12)C+^(12)C fusion reaction was studied in the range of E_(c.m.)=8.9 to 21 MeV using the active-target Time Projection Chamber.With full information on all tracks of the reaction products,cross sections of the^(...The ^(12)C+^(12)C fusion reaction was studied in the range of E_(c.m.)=8.9 to 21 MeV using the active-target Time Projection Chamber.With full information on all tracks of the reaction products,cross sections of the^(12)C(^(12)C,^(8)Be)^(16)O_(g.s.)channel and the ^(12)C(^(12)C,3a)^(12)C channel could be measured down to the level of a few milibarns.The ^(12)C(^(12)C,^(8)Be)^(16)O_(g.s.)reaction channel was determined to be 10_(-8)^(+24) mb at E_(c.m.)=11.1 MeV,supporting the direct a transfer reaction mechanism.The ^(12)C(^(12)C,3α)^(12)C reaction channel was studied for the first time using an exclusive measurement.Our result does not confirm the anomaly behavior reported in the previous inclusive measurement by Kolata et al.[Phys.Rev.C 21,579(1980)].Our comparisons with statistical model calculations suggest that the 3 a channel is dominated by the fusion evaporation process at E_(c.m.)>19 MeV.The additional contribution of the 3 a channel increases the fusion reaction cross section by 10% at energies above 20 MeV.We also find that an additional reaction mechanism is needed to explain the measured cross section at E_(c.m.)<15 MeV at which point the statistical model prediction vanishes.展开更多
Brain metastasis is a major cause of death in patients with solid cancers. Breast cancer cells have high tendency to migrate towards brain. Cancer cells within brain are characterized by severe aggressiveness and inac...Brain metastasis is a major cause of death in patients with solid cancers. Breast cancer cells have high tendency to migrate towards brain. Cancer cells within brain are characterized by severe aggressiveness and inaccessibility. Currently, breast cancer and its metastasis are the second leading cause of death among women. Tumor microenvironment and blood brain barrier (BBB) represent great obstacles in targeting breast cancer and its metastasis. Chemotherapy is a safer treatment modality for brain metastasis compared with risky surgical resection and brain radiotherapy. Unfortunately, conventional chemotherapy lack penetration of BBB and suffer from multiple resistance mechanisms. Current treatment technologies for brain metastases of breast cancer have limited long-term success and numerous side effects, illustrating the urgent need for novel smart strategies. Various novel drug entities and nanosystems have been employed to improve diagnosis and targeted treatment of breast cancer and its metastasis. Immunotherapy agents and small tyrosine kinase inhibitors have been shown to reduce tumor size and increase survival in patients with breast cancer, but still poorly penetrate BBB. Tailored sized nanoparticles to some extent crossed brain tumor barrier and enhanced drug accumulation in tumors by taking advantage of enhanced permeability and retention. Furthermore, various active targeting strategies have been adopted to improve accessibility to brain malignancies. Therefore, to achieve enhanced antitumor therapy against ;breast cancer and its brain metastasis, multi-talented delivery systems are urgently needed for optimal treatment. This review focuses on the various active and passive targeting technologies for the treatment of breast cancer brain metastases in the past decade. A comprehensive summary and examples along with pros and cons of each system will be discussed. Different treatment modalities and nanotechnology facilities will be demonstrated to aid in designing the optimal smart, safe, targeted and effective systems to combat brain metastases of breast cancer.展开更多
Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions.Herein,we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation ...Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions.Herein,we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop.The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate(MTX)self-assembles into nanoparticles(VSeM);decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time.Upon reaching tumor sites,acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake.Afterward,the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release;then the released VES could produce extra ROS to accelerate the collapse of VSeM.Finally,the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy.Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment.展开更多
Targeted delivery of therapeutics for spinal cord injury(SCI)has been a long-term challenge due to the complexity of the pathological procession.Macrophage,as an immune cell,can selectively accumulate at the trauma si...Targeted delivery of therapeutics for spinal cord injury(SCI)has been a long-term challenge due to the complexity of the pathological procession.Macrophage,as an immune cell,can selectively accumulate at the trauma site after SCI.This intrinsic targeting,coupled with good immune-escaping capacity makes macrophages an ideal source of biomimetic delivery carrier for SCI.Worth mentioning,macrophages have multiple polarization states,which may not be ignored when designing macrophage-based delivery systems.Herein,we fabricated macrophage membrane-camouflaged liposomes(RM-LIPs)and evaluated their abilities to extend drug circulation time and target the injured spinal cord.Specially,we detected the expression levels of the two main targeted receptors Mac-1 and integrinα4 in three macrophage subtypes,including unactivated(M0)macrophages,classically activated(M1)macrophages and alternatively activated(M2)macrophages,and compared targeting of these macrophage membrane-coated nanoparticles for SCI.The macrophage membrane camouflage decreased cellular uptake of liposomes in RAW264.7 immune cells and strengthened binding of the nanoparticle to the damaged endothelial cells in vitro.RM-LIPs can prolong drug circulation time and actively accumulate at the trauma site of the spinal cord in vivo.Besides,RM-LIPs loaded with minocycline(RM-LIP/MC)showed a comprehensive therapeutic effect on SCI mice,and the anti-pyroptosis was found to be a novel mechanism of RM-LIP/MC treatment of SCI.Moreover,the levels of Mac-1 and integrinα4 in macrophages and the targeting of RM-LIP for SCI were found to be independent of macrophage polarization states.Our study provided a biomimetic strategy via the biological properties of macrophages for SCI targeting and treatment.展开更多
Waxy maize is a specialty maize that produces mainly amylopectin starch with special food or industrial values. The objective of this study was to overcome the limitations of wx mutant allele acquisition and breeding ...Waxy maize is a specialty maize that produces mainly amylopectin starch with special food or industrial values. The objective of this study was to overcome the limitations of wx mutant allele acquisition and breeding efficiency by conversion of parental lines from normal to waxy maize. The intended mutation activity was achieved by in vivo CRISPR/Cas9 machinery involving desired-target mutation of the Wx locus in the ZC01 background,abbreviated as ZC01-DTM^(wx). Triple selection was applied to segregants to obtain high genome background recovery with transgene-free wx mutations. The targeted mutation was identified, yielding six types of mutations among progeny crossed with ZC01-DTM^(wx).The amylopectin contents of the endosperm starch in mutant lines and hybrids averaged94.9%, while those of the wild-type controls were significantly(P < 0.01) lower, with an average of 76.9%. Double selection in transgene-free lines was applied using the Bar strip test and Cas9 PCR screening. The genome background recovery ratios of the lines were determined using genome-wide SNP data. That of lines used as male parents was as high as98.19% and that of lines used as female parents was as high as 86.78%. Conversion hybrids and both parental lines showed agronomic performance similar to that of their wild-type counterparts. This study provides a practical example of the efficient extension of CRISPR/Cas9 targeted mutation to industrial hybrids for transformation of a recalcitrant species.展开更多
Although the benefits of China’s trade expansion have been distributed much more broadly than those of some early industrialized nations,China has become the primary target of anti-dumping activities.Being a new and ...Although the benefits of China’s trade expansion have been distributed much more broadly than those of some early industrialized nations,China has become the primary target of anti-dumping activities.Being a new and relatively efficient new rival in the global market may be an important reason for this.On the other hand,China’s development stage and her trade structure also place her in a disadvantageous position when it comes to anti-dumping activities.展开更多
Microbubbles can enhance the detection in noninvasive ultrasound imaging.Recently,targeted microbubbles have been developed to selectively adhere to specific and overexpressed p molecules in endothelial cells in some ...Microbubbles can enhance the detection in noninvasive ultrasound imaging.Recently,targeted microbubbles have been developed to selectively adhere to specific and overexpressed p molecules in endothelial cells in some pathologic conditions.However,the law of展开更多
Developing agents that can accurately differentiate tumors from normal healthy tissues is of utmost importance for safe cancer therapy.Active targeting has been considered as an effective technique for tumor recogniti...Developing agents that can accurately differentiate tumors from normal healthy tissues is of utmost importance for safe cancer therapy.Active targeting has been considered as an effective technique for tumor recognition.In this work,we demonstrate a folate-functionalized nanoscale covalent organic framework(FATD nCOF)highly specific to cancer cells through active targeting of their enriched folate receptors(FRs).The FATD nCOF prepared by simple post-synthetic modification of the COF surface defeats disperses well in water and exhibits a high loading capacity for various anticancer drugs.The biocompatible FATD nCOF is selectively internalized by FR-harboring cancer cells and consequently augments the efficacy of the loaded drug,Withaferin A(Wi-A),for targeted cancer cell killing.In biomolecular mechanism studies,Wi-A-loaded FATD(FATD@Wi-A)nanocomposites show remarkably a higher rate of apoptosis in FR-enriched cancer cells.Comparative analyses of FR-positive and FR-negative tumor xenografts reveal enhanced selective antitumor activity of FATD@Wi-A nanotherapeutics.Taken together,the study findings suggest that FATD nCOF holds great promise for active targeting of tumors in vivo.Our simple yet effective technology might be valuable for creating new state-of-the-art COFs for chemical and biomedical applications.展开更多
Objective:In this study,we aimed to develop an amino-terminal fragment(ATF)peptide-targeted liposome carryingβ-elemene(ATF24-PEG-Lipo-β-E)for targeted delivery into urokinase plasminogen activator receptor-overexpre...Objective:In this study,we aimed to develop an amino-terminal fragment(ATF)peptide-targeted liposome carryingβ-elemene(ATF24-PEG-Lipo-β-E)for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin(DDP)for bladder cancer treatment.Methods:The liposomes were prepared by ethanol injection and high-pressure microjet homogenization.The liposomes were characterized,and the drug content,entrapment efficiency,andin vitro release were studied.The targeting efficiency was investigated using confocal microscopy,ultra-fast liquid chromatography,and an orthotopic bladder cancer model.The effects of ATF24-PEG-Lipo-β-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8(CCK-8)assay,a colony formation assay,and cell apoptosis and cell cycle analyses.The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model.Results:ATF24-PEG-Lipo-β-E had small and uniform sizes(~79 nm),high drug loading capacity(~5.24 mg/mL),high entrapment efficiency(98.37±0.95%),and exhibited sustained drug release behavior.ATF24-PEG-Lipo-β-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol(PEG)ylatedβ-elemene liposomes(PEG-Lipo-β-E).DDP,combined with ATF24-PEG-Lipo-β-E,exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase,and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways.Furthermore,thein vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors,using the combined strategy.Conclusions:The present study provided an effective strategy for the targeted delivery ofβ-elemene(β-E)to bladder cancer,and a combined strategy for bladder cancer treatment.展开更多
Objective:To compare the targeting effects of lactosarninated alginate(AlgNP)、polyethylene glycol - coated hydroxyapatite- poly- L- lysine nanoparticles (PLL- PCHNP)and relative nonlactosaminated ones load ed with ex...Objective:To compare the targeting effects of lactosarninated alginate(AlgNP)、polyethylene glycol - coated hydroxyapatite- poly- L- lysine nanoparticles (PLL- PCHNP)and relative nonlactosaminated ones load ed with exogenous gene on liver via peripheral intravenous route. Methods:Preparation of AlgNP based on control of gelification phenomenon of algiante by calcium ions and HA- PLLNP with collosol - gel method, both further modified with lactosaminated - poly- L - lysine synthesized by reductive lactosamination . We used pEGFPCl as the reporter gene to establish receptor- mediated and positive liver targeting nanoparticles- gene model. The potential of adsorbing DNA on nanoparticles was analysed by electrophoresis and spectrophotometer. Then different complexes were transferred into the rat's body by peripheral intravenous route and their targeting characteristics in liver were investigated by using radioisotope tracing assay. Results: PCHNP presented as needle - like particles with a diameter of 20nm by TEM and could be effectively combined with PLL. The diameter of AlgNP was 280nm. Agarpse gel electrophoresis showed both nanoparticles could effectively combine with DNA and the optimal proportion of PLLPCHNP and DNA was 30:1 (w/w); DNA mixed ratio of AlgPLL was 68.3 % by spectrophotometer. The radioactivities in liver for the two lactosaminated nanoparticles were higher than the nonlactosaminated ones. No statistic difference between AlgNP and AlgLacNP could be found . Conclusions: Lactosaminated naroparticles can target to liver more effectively by peripheral intravenous route than nonlactosaminated ones, which is closely concerned with the characteritics of the nanopartide complex.展开更多
The properties of modified biomaterial are gaining more and more importance in drug delivery systems.Sialic acid(SA)and polysialic acid(PSA)serve as endogenous substances,which are non-immunogenic and biodegradable.At...The properties of modified biomaterial are gaining more and more importance in drug delivery systems.Sialic acid(SA)and polysialic acid(PSA)serve as endogenous substances,which are non-immunogenic and biodegradable.At the same time,SA modification of the drugs/carriers can enhance the uptake of tumor cell and retention in brain;PSA modifi-cation can reduce the immunogenicity of the proteins or polypeptides and increase circulation time of the modified drugs/carriers in the blood,thus achieving active targeting effect.These properties offer a variety of opportunities for applications in drug delivery systems.This article summarizes the biological functions of SA and PSA and presents the technologies of SA/PSA modified small molecule drugs,proteins and carriers in drug delivery systems.展开更多
A novel type of amphiphilic pH-responsive folate-poly(ε-caprolactone)- block-poly( 2-hydroxyethylmethacrylate )-co-poly( 2-( dimethylamino )-ethylmethacrylate ) (FA-PCL-b-P(HEMA-co-DMAEMA)) (MFP) block ...A novel type of amphiphilic pH-responsive folate-poly(ε-caprolactone)- block-poly( 2-hydroxyethylmethacrylate )-co-poly( 2-( dimethylamino )-ethylmethacrylate ) (FA-PCL-b-P(HEMA-co-DMAEMA)) (MFP) block copolymers were designed and synthe- sized via atom transfer radical polymerization (ATRP) and ring opening polymerization (ROP) techniques. The molecular structures of the copolymers were confirmed with IH NMR, FTIR and GPC measurements. The critical micelle concentration (CMC) of MFP in aqueous solution was extremely low (about 6.54 mglL). The in vitro release behavior of DOX-Ioaded micelles was significantly accelerated when the pH value of solution decreased from 7.4 to 5.0. In vitro antitumor efficiency was evaluated by incubating DOX- loaded micelles with Hela cells. The results demonstrated that this copolymer possessed excellent biocompatibility, and FA-decorated micelles MFP showed higher cellular uptake than those micelles without the FA moiety, indicating their unique targetability. These folate-conjugated biodegradable micelles are highly promising for targeted cancer chemothe-rapy.展开更多
Confining chemotherapy to tumour sites by means of active targeting nanoparticles(NPs)may increase the treatment effectuality while reducing potential side effects.Cubosomes are one of the next-generation drug deliver...Confining chemotherapy to tumour sites by means of active targeting nanoparticles(NPs)may increase the treatment effectuality while reducing potential side effects.Cubosomes are one of the next-generation drug delivery nanocarriers by virtue of their biocompatibility and bioadhesion,sizeable payload encapsulation and high thermostability.Herein,an active tumour targeting system towards rhabdomyosarcoma(RMS)cells was evaluated.Cubosomes were loaded with helenalin(a secondary metabolite from Arnica plants),which we have previously shown to induce apoptosis in RMS cells.The functionalization of the cubosomes was accomplished to enable binding to membrane receptors and translocation under a magnetic field.RMS cells overexpress CD44 and CD221 on their membrane surface and,therefore,hyaluronic acid(HA,a ligand for CD44)and antibodies(Abs)against CD221 were coupled to cubosomes via electrostatic attraction and the thiol-Michael reaction,respectively.Magnetization of the cubic phase NPs was achieved by embedding superparamagnetic iron oxide NPs(SPIONPs)into the cubic matrix.Single-function and multi-function cubosomes had Im3m cubic phase structures with well-organized lattice patterns.Conjugation with 2%HA or anti-CD221 half Abs and/or 1%SPIONPs showed significantly higher uptake into RMS cells compared to unfunctionalized cubosomes.CD44 and CD221 directed magnetic(triple-function)cubosomes were capable of internalizing into RMS cells in an energy-independent mechanism.Helenalin-laden triple functionalized cubosomes showed limited impact on the viability of control fibroblast cells,while they induced a high degree cytotoxicity against RMS cells.Profound tumour cell death was observed in both two-dimensional(2D)culture and three-dimensional(3D)tumour spheroids.展开更多
Proton exchange membrane fuel cells(PEMFC)have attracted much attention because of their high energy conversion efficiency,high power density and zero emission of pollutants.However,the high cost of the cathode platin...Proton exchange membrane fuel cells(PEMFC)have attracted much attention because of their high energy conversion efficiency,high power density and zero emission of pollutants.However,the high cost of the cathode platinum group metal(PGM)catalysts creates a barrier for the large-scale application of PEMFC.Tremendous efforts have been devoted to the development of low-cost PGM-free catalysts,especially the Fe-N-C catalysts,to replace the expensive PGM catalysts.However,the characterization methods and evaluation standards of the catalysts varies,which is not conducive to the comparison of PGM-free catalysts.U.S.Department of energy(DOE)is the only authority that specifies the testing standards and activity targets for PGM-free catalysts.In this review,the major breakthroughs of Fe-N-C catalysts are outlined with the reference of DOE standards and targets.The preparation and characteristics of these highly active Fe-N-C catalysts are briefly introduced.Moreover,the efforts on improving the mass transfer and the durability issue of Fe-N-C fuel cell are discussed.Finally,the prospective directions concerning the comprehensive evaluation of the Fe-N-C catalysts are proposed.展开更多
A tracking filter algorithm based on the maneuvering detection delay is presented in order to solve the fuzzy problem of target maneuver decision introduced by the measure?ment errors of active sonar. When the maneuv...A tracking filter algorithm based on the maneuvering detection delay is presented in order to solve the fuzzy problem of target maneuver decision introduced by the measure?ment errors of active sonar. When the maneuvering detection is unclear, two target moving hypotheses, the uniform and the maneuver, derived from the method of multiple hypothesis tracking, are generated to delay the final decision time. Then the hypothesis test statistics is constructed by using the residual sequence. The active sonar?s tracking ability of unknown prior information targets is improved due to the modified sequential probability ratio test and the integration of the advantages of strong tracking filter and the Kalman filter. Simulation results show that the algorithm is able to not only track the uniform targets accurately, but also track the maneuvering targets steadily. The effectiveness of the algorithm for real underwater acoustic targets is further verified by the sea trial data processing results.展开更多
Inflammatory bowel disease(IBD)is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization.With no curative therapy for IBD at present,the development of effective therapeutics...Inflammatory bowel disease(IBD)is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization.With no curative therapy for IBD at present,the development of effective therapeutics is highly advocated.Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention(EPR)effect caused by the inflammation.However,the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release.Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs,ligandmodified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects.This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands.Finally,challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.展开更多
Binary asymmetric nanocrystals (BNCs), composed of a photoactive TiO2 nanorod joined with a superparamagnetic γ-Fe203 spherical domain, were embedded in polyethylene glycol modified phospholipid micelle and success...Binary asymmetric nanocrystals (BNCs), composed of a photoactive TiO2 nanorod joined with a superparamagnetic γ-Fe203 spherical domain, were embedded in polyethylene glycol modified phospholipid micelle and successfully bioconjugated to a suitably designed peptide containing an RGD motif. BNCs represent a relevant multifunctional nanomaterial, owing to the coexistence of two distinct domains in one particle, characterized by high photoactivity and magnetic properties, that is particularly suited for use as a phototherapy and hyperthermia agent as well as a magnetic probe in biological imaging. We selected the RGD motif in order to target integrin expressed on activated endothelial cells and several types of cancer cells. The prepared RGD-peptide/BNC conjugates, comprehensively monitored by using complementary optical and structural techniques, demon- strated a high stability and uniform dispersibility in biological media. The cytotoxicity of the RGD-peptide/BNC conjugates was studied in vitro. The cellular uptake of RGD-peptide conjugates in the cells, assessed by means of two distinct approaches, namely confocal microscopy analysis and emission spectroscopy determination in cell lysates, displayed selectivity of the RGD-peptide-BNC conjugate for the cw]33 integrin. These RGD-peptide-BNC conjugates have a high potential for theranostic treatment of cancer.展开更多
Hyperbranched polysulfonamine (HPSA) is a promising biomaterial due to its highly branched spherical architecture and efficient intracellular translocation. To realize the fianctionalization of HPSA, both N-succinim...Hyperbranched polysulfonamine (HPSA) is a promising biomaterial due to its highly branched spherical architecture and efficient intracellular translocation. To realize the fianctionalization of HPSA, both N-succinimidyl 3-(2- pyridyldithio) propionate (SPDP) for tethering the human-mouse chimeric monoclonal antibody CH12 and N-hydroxy succinimidyl S-acetylmercaptoacetyltriglycinate (NHS-MAG3) for labeling 188Re were sequentially grafted onto the primary amine terminals of HPSA via covalent linkages, attaining the SPDP-HPSA-MAG3 intermediate. In order to reserve the structural integrity of CH12, the fragment crystallizable (Fc) region was also processed by oxidation of oligosaccharide moieties with sodium periodate and then reacted with N-(κ-maleimidoundecanoic acid) hydrazide (KMUH). After chelating 188Re with MAG3 group, the SPDP was reduced to PDP and connected onto the maleinimide group at the Fc region. As a result, both the epidermal growth factor receptor viii (EGFRvIII) targeted monoclonal antibody CH12 and the radionuclide 188Re were conjugated to the HPSA-based vehicles, forming the 188Re-labeled and CH12-tethered HPSA (CH12-HPSA- 188Re). The molecular weight and in vitro stability of CH12-HPSA-188Re were evaluated by gel electrophoresis and paper chromatography. On one hand, the CH12-HPSA-188Re could specifically bind to the EGFRvlII-positive human hepatocarcinoma cells in vitro. On the other hand, it could also target at the tumor tissue of nude mice in vivo. Hence, the CH12-HPSA-188Re could effectively target at the human hepatocarcinoma and facilitate the tumor detection and targeted radioimmunotherapy.展开更多
A charged particle array named MATE-PA,which serves as an auxiliary detector system for a Multi-purpose Active-target Time projection chamber used in nuclear astrophysical and exotic beam Experiments(MATE),was constru...A charged particle array named MATE-PA,which serves as an auxiliary detector system for a Multi-purpose Active-target Time projection chamber used in nuclear astrophysical and exotic beam Experiments(MATE),was constructed.The array comprised of 20 single-sided strip-silicon detectors covering approximately 10%of the solid angle.The detectors facilitated the detection of reaction-induced charged particles that penetrate the active volume of the MATE.The performance of MATE-PA has been experimentally studied using an alpha source and a 36-MeV 14 N beam injected into the MATE chamber on the radioactive ion beam line in Lanzhou(RIBLL).The chamber was filled with a gas mixture of 95%4 He and 5%CO_2 at a pressure of 500 mbar.The results indicated good separation of light-charged particles using the forward double-layer silicon detectors of MATE-PA.The energy resolution of the Si detectors was deduced to be approximately 1%(σ)for an energy loss of approximately 10 MeV caused by theαparticles.The inclusion of MATE-PA improves particle identification and increases the dynamic range of the kinetic energy of charged particles,particularly that of theαparticles,up to approximately 15 MeV.展开更多
文摘This article mainly introduced novel carrier-modified methods for active targeting antitumor preparation as well as their evaluation methodology in recent years. By reviewing related domestic and overseas literatures, the up-to-date scientific researches concerning active targeting antitumor preparation were elaborated and the problems existing in present studies were discussed. Numerous valid vector- embellished methods had been discovered with excellent targeting effects, and the significant progress was acquired for the evaluation tools in vitroand in vivo. The active targeting agent would be a major direction in prospective tumor or cancer therapeutic regimen.
基金Supported in part by the Strategic Priority Research Program of Chinese Academy of Sciences(XDB34020200)the National Key Research and Development program(MOST 2016YFA0400501)from the Ministry of Science and Technology of China+2 种基金the State Key Laboratory of Nuclear Physics and Technology,PKU(NPT2020KFY06)the National Natural Science Foundation of China(U1632142,12175156),the National Natural Science Foundation of China(11905260)the Western Light Project of Chinese Academy of Sciences。
文摘The ^(12)C+^(12)C fusion reaction was studied in the range of E_(c.m.)=8.9 to 21 MeV using the active-target Time Projection Chamber.With full information on all tracks of the reaction products,cross sections of the^(12)C(^(12)C,^(8)Be)^(16)O_(g.s.)channel and the ^(12)C(^(12)C,3a)^(12)C channel could be measured down to the level of a few milibarns.The ^(12)C(^(12)C,^(8)Be)^(16)O_(g.s.)reaction channel was determined to be 10_(-8)^(+24) mb at E_(c.m.)=11.1 MeV,supporting the direct a transfer reaction mechanism.The ^(12)C(^(12)C,3α)^(12)C reaction channel was studied for the first time using an exclusive measurement.Our result does not confirm the anomaly behavior reported in the previous inclusive measurement by Kolata et al.[Phys.Rev.C 21,579(1980)].Our comparisons with statistical model calculations suggest that the 3 a channel is dominated by the fusion evaporation process at E_(c.m.)>19 MeV.The additional contribution of the 3 a channel increases the fusion reaction cross section by 10% at energies above 20 MeV.We also find that an additional reaction mechanism is needed to explain the measured cross section at E_(c.m.)<15 MeV at which point the statistical model prediction vanishes.
文摘Brain metastasis is a major cause of death in patients with solid cancers. Breast cancer cells have high tendency to migrate towards brain. Cancer cells within brain are characterized by severe aggressiveness and inaccessibility. Currently, breast cancer and its metastasis are the second leading cause of death among women. Tumor microenvironment and blood brain barrier (BBB) represent great obstacles in targeting breast cancer and its metastasis. Chemotherapy is a safer treatment modality for brain metastasis compared with risky surgical resection and brain radiotherapy. Unfortunately, conventional chemotherapy lack penetration of BBB and suffer from multiple resistance mechanisms. Current treatment technologies for brain metastases of breast cancer have limited long-term success and numerous side effects, illustrating the urgent need for novel smart strategies. Various novel drug entities and nanosystems have been employed to improve diagnosis and targeted treatment of breast cancer and its metastasis. Immunotherapy agents and small tyrosine kinase inhibitors have been shown to reduce tumor size and increase survival in patients with breast cancer, but still poorly penetrate BBB. Tailored sized nanoparticles to some extent crossed brain tumor barrier and enhanced drug accumulation in tumors by taking advantage of enhanced permeability and retention. Furthermore, various active targeting strategies have been adopted to improve accessibility to brain malignancies. Therefore, to achieve enhanced antitumor therapy against ;breast cancer and its brain metastasis, multi-talented delivery systems are urgently needed for optimal treatment. This review focuses on the various active and passive targeting technologies for the treatment of breast cancer brain metastases in the past decade. A comprehensive summary and examples along with pros and cons of each system will be discussed. Different treatment modalities and nanotechnology facilities will be demonstrated to aid in designing the optimal smart, safe, targeted and effective systems to combat brain metastases of breast cancer.
基金This work was partially supported by the National Natural Science Foundation of China(Grant Nos.81871483,81671813 and 61727823)the open project funding of The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province(Grant No.2018ZDSY2001).
文摘Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions.Herein,we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop.The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate(MTX)self-assembles into nanoparticles(VSeM);decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time.Upon reaching tumor sites,acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake.Afterward,the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release;then the released VES could produce extra ROS to accelerate the collapse of VSeM.Finally,the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy.Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment.
基金supported by the National Natural Science Foundation of China(No.81673376)the National Natural Science Foundation of Chongqing(cstc2015jcyj BX0100)the project for innovative Research Group at Higher Educational Institutions in Chongqing(CXQT20006)。
文摘Targeted delivery of therapeutics for spinal cord injury(SCI)has been a long-term challenge due to the complexity of the pathological procession.Macrophage,as an immune cell,can selectively accumulate at the trauma site after SCI.This intrinsic targeting,coupled with good immune-escaping capacity makes macrophages an ideal source of biomimetic delivery carrier for SCI.Worth mentioning,macrophages have multiple polarization states,which may not be ignored when designing macrophage-based delivery systems.Herein,we fabricated macrophage membrane-camouflaged liposomes(RM-LIPs)and evaluated their abilities to extend drug circulation time and target the injured spinal cord.Specially,we detected the expression levels of the two main targeted receptors Mac-1 and integrinα4 in three macrophage subtypes,including unactivated(M0)macrophages,classically activated(M1)macrophages and alternatively activated(M2)macrophages,and compared targeting of these macrophage membrane-coated nanoparticles for SCI.The macrophage membrane camouflage decreased cellular uptake of liposomes in RAW264.7 immune cells and strengthened binding of the nanoparticle to the damaged endothelial cells in vitro.RM-LIPs can prolong drug circulation time and actively accumulate at the trauma site of the spinal cord in vivo.Besides,RM-LIPs loaded with minocycline(RM-LIP/MC)showed a comprehensive therapeutic effect on SCI mice,and the anti-pyroptosis was found to be a novel mechanism of RM-LIP/MC treatment of SCI.Moreover,the levels of Mac-1 and integrinα4 in macrophages and the targeting of RM-LIP for SCI were found to be independent of macrophage polarization states.Our study provided a biomimetic strategy via the biological properties of macrophages for SCI targeting and treatment.
基金supported the National Transgenic Science and Technology Program(2019ZX08010-003)the National Natural Science Foundation of China(31771808)+3 种基金the National Key Research and Development Program of China(2016YFD0101803)the Key Area Research and Development Program of Guangdong Province(2018B020202008)Beijing Municipal Science and Technology Commission(D171100007717001)National Engineering Laboratory for Crop Molecular Breeding。
文摘Waxy maize is a specialty maize that produces mainly amylopectin starch with special food or industrial values. The objective of this study was to overcome the limitations of wx mutant allele acquisition and breeding efficiency by conversion of parental lines from normal to waxy maize. The intended mutation activity was achieved by in vivo CRISPR/Cas9 machinery involving desired-target mutation of the Wx locus in the ZC01 background,abbreviated as ZC01-DTM^(wx). Triple selection was applied to segregants to obtain high genome background recovery with transgene-free wx mutations. The targeted mutation was identified, yielding six types of mutations among progeny crossed with ZC01-DTM^(wx).The amylopectin contents of the endosperm starch in mutant lines and hybrids averaged94.9%, while those of the wild-type controls were significantly(P < 0.01) lower, with an average of 76.9%. Double selection in transgene-free lines was applied using the Bar strip test and Cas9 PCR screening. The genome background recovery ratios of the lines were determined using genome-wide SNP data. That of lines used as male parents was as high as98.19% and that of lines used as female parents was as high as 86.78%. Conversion hybrids and both parental lines showed agronomic performance similar to that of their wild-type counterparts. This study provides a practical example of the efficient extension of CRISPR/Cas9 targeted mutation to industrial hybrids for transformation of a recalcitrant species.
文摘Although the benefits of China’s trade expansion have been distributed much more broadly than those of some early industrialized nations,China has become the primary target of anti-dumping activities.Being a new and relatively efficient new rival in the global market may be an important reason for this.On the other hand,China’s development stage and her trade structure also place her in a disadvantageous position when it comes to anti-dumping activities.
基金supported by National Natural Science Foundation of China,No.30700151
文摘Microbubbles can enhance the detection in noninvasive ultrasound imaging.Recently,targeted microbubbles have been developed to selectively adhere to specific and overexpressed p molecules in endothelial cells in some pathologic conditions.However,the law of
基金the Japan Society for the Promotion of Science(JSPS)KAKENHI Grant-in-Aid for Early-Career Scientists(No.21K14508)Takeda Science Foundation+4 种基金Advanced Technology Institute Research Grants 2021Senri Life Science FoundationMurata Science Foundation,JST CREST Grant(No.JPMJCR21B3)grants from AIST(Japan)and the Department of Biotechnology(Govt.of India)under the DAILAB and DAICENTER projectsthe National Key Research and Development Program of China(No.2022YFF0710705).
文摘Developing agents that can accurately differentiate tumors from normal healthy tissues is of utmost importance for safe cancer therapy.Active targeting has been considered as an effective technique for tumor recognition.In this work,we demonstrate a folate-functionalized nanoscale covalent organic framework(FATD nCOF)highly specific to cancer cells through active targeting of their enriched folate receptors(FRs).The FATD nCOF prepared by simple post-synthetic modification of the COF surface defeats disperses well in water and exhibits a high loading capacity for various anticancer drugs.The biocompatible FATD nCOF is selectively internalized by FR-harboring cancer cells and consequently augments the efficacy of the loaded drug,Withaferin A(Wi-A),for targeted cancer cell killing.In biomolecular mechanism studies,Wi-A-loaded FATD(FATD@Wi-A)nanocomposites show remarkably a higher rate of apoptosis in FR-enriched cancer cells.Comparative analyses of FR-positive and FR-negative tumor xenografts reveal enhanced selective antitumor activity of FATD@Wi-A nanotherapeutics.Taken together,the study findings suggest that FATD nCOF holds great promise for active targeting of tumors in vivo.Our simple yet effective technology might be valuable for creating new state-of-the-art COFs for chemical and biomedical applications.
基金This research was supported by grants from the National Natural Science Foundation of China(Grant Nos.81672932,81730108,81874380,and 81973635)Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars(Grant No.LR18H160001)the Zhejiang Province Science and Technology Project of TCM(Grant No.2019ZZ016).
文摘Objective:In this study,we aimed to develop an amino-terminal fragment(ATF)peptide-targeted liposome carryingβ-elemene(ATF24-PEG-Lipo-β-E)for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin(DDP)for bladder cancer treatment.Methods:The liposomes were prepared by ethanol injection and high-pressure microjet homogenization.The liposomes were characterized,and the drug content,entrapment efficiency,andin vitro release were studied.The targeting efficiency was investigated using confocal microscopy,ultra-fast liquid chromatography,and an orthotopic bladder cancer model.The effects of ATF24-PEG-Lipo-β-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8(CCK-8)assay,a colony formation assay,and cell apoptosis and cell cycle analyses.The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model.Results:ATF24-PEG-Lipo-β-E had small and uniform sizes(~79 nm),high drug loading capacity(~5.24 mg/mL),high entrapment efficiency(98.37±0.95%),and exhibited sustained drug release behavior.ATF24-PEG-Lipo-β-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol(PEG)ylatedβ-elemene liposomes(PEG-Lipo-β-E).DDP,combined with ATF24-PEG-Lipo-β-E,exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase,and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways.Furthermore,thein vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors,using the combined strategy.Conclusions:The present study provided an effective strategy for the targeted delivery ofβ-elemene(β-E)to bladder cancer,and a combined strategy for bladder cancer treatment.
文摘Objective:To compare the targeting effects of lactosarninated alginate(AlgNP)、polyethylene glycol - coated hydroxyapatite- poly- L- lysine nanoparticles (PLL- PCHNP)and relative nonlactosaminated ones load ed with exogenous gene on liver via peripheral intravenous route. Methods:Preparation of AlgNP based on control of gelification phenomenon of algiante by calcium ions and HA- PLLNP with collosol - gel method, both further modified with lactosaminated - poly- L - lysine synthesized by reductive lactosamination . We used pEGFPCl as the reporter gene to establish receptor- mediated and positive liver targeting nanoparticles- gene model. The potential of adsorbing DNA on nanoparticles was analysed by electrophoresis and spectrophotometer. Then different complexes were transferred into the rat's body by peripheral intravenous route and their targeting characteristics in liver were investigated by using radioisotope tracing assay. Results: PCHNP presented as needle - like particles with a diameter of 20nm by TEM and could be effectively combined with PLL. The diameter of AlgNP was 280nm. Agarpse gel electrophoresis showed both nanoparticles could effectively combine with DNA and the optimal proportion of PLLPCHNP and DNA was 30:1 (w/w); DNA mixed ratio of AlgPLL was 68.3 % by spectrophotometer. The radioactivities in liver for the two lactosaminated nanoparticles were higher than the nonlactosaminated ones. No statistic difference between AlgNP and AlgLacNP could be found . Conclusions: Lactosaminated naroparticles can target to liver more effectively by peripheral intravenous route than nonlactosaminated ones, which is closely concerned with the characteritics of the nanopartide complex.
基金the National Natural Science Foundation of China(Grant No.81373334).
文摘The properties of modified biomaterial are gaining more and more importance in drug delivery systems.Sialic acid(SA)and polysialic acid(PSA)serve as endogenous substances,which are non-immunogenic and biodegradable.At the same time,SA modification of the drugs/carriers can enhance the uptake of tumor cell and retention in brain;PSA modifi-cation can reduce the immunogenicity of the proteins or polypeptides and increase circulation time of the modified drugs/carriers in the blood,thus achieving active targeting effect.These properties offer a variety of opportunities for applications in drug delivery systems.This article summarizes the biological functions of SA and PSA and presents the technologies of SA/PSA modified small molecule drugs,proteins and carriers in drug delivery systems.
基金This work was supported financially by the National Natural Science Foundation of China (Grant Nos. 21367022, 51662036 and 21664013) and the Bingtuan Innovation Team in Key Areas (2015BD003).
文摘A novel type of amphiphilic pH-responsive folate-poly(ε-caprolactone)- block-poly( 2-hydroxyethylmethacrylate )-co-poly( 2-( dimethylamino )-ethylmethacrylate ) (FA-PCL-b-P(HEMA-co-DMAEMA)) (MFP) block copolymers were designed and synthe- sized via atom transfer radical polymerization (ATRP) and ring opening polymerization (ROP) techniques. The molecular structures of the copolymers were confirmed with IH NMR, FTIR and GPC measurements. The critical micelle concentration (CMC) of MFP in aqueous solution was extremely low (about 6.54 mglL). The in vitro release behavior of DOX-Ioaded micelles was significantly accelerated when the pH value of solution decreased from 7.4 to 5.0. In vitro antitumor efficiency was evaluated by incubating DOX- loaded micelles with Hela cells. The results demonstrated that this copolymer possessed excellent biocompatibility, and FA-decorated micelles MFP showed higher cellular uptake than those micelles without the FA moiety, indicating their unique targetability. These folate-conjugated biodegradable micelles are highly promising for targeted cancer chemothe-rapy.
基金supported by the Pyongyang University of Science and Technology(PUST)-UK scholarship,the Williams Fund(Oxford Hospitals Charity,No.0085)the UK national electron bio-imaging centre(No.NT32452)the Marie Sklodowska–Curie Grant Agreement(No.840964).
文摘Confining chemotherapy to tumour sites by means of active targeting nanoparticles(NPs)may increase the treatment effectuality while reducing potential side effects.Cubosomes are one of the next-generation drug delivery nanocarriers by virtue of their biocompatibility and bioadhesion,sizeable payload encapsulation and high thermostability.Herein,an active tumour targeting system towards rhabdomyosarcoma(RMS)cells was evaluated.Cubosomes were loaded with helenalin(a secondary metabolite from Arnica plants),which we have previously shown to induce apoptosis in RMS cells.The functionalization of the cubosomes was accomplished to enable binding to membrane receptors and translocation under a magnetic field.RMS cells overexpress CD44 and CD221 on their membrane surface and,therefore,hyaluronic acid(HA,a ligand for CD44)and antibodies(Abs)against CD221 were coupled to cubosomes via electrostatic attraction and the thiol-Michael reaction,respectively.Magnetization of the cubic phase NPs was achieved by embedding superparamagnetic iron oxide NPs(SPIONPs)into the cubic matrix.Single-function and multi-function cubosomes had Im3m cubic phase structures with well-organized lattice patterns.Conjugation with 2%HA or anti-CD221 half Abs and/or 1%SPIONPs showed significantly higher uptake into RMS cells compared to unfunctionalized cubosomes.CD44 and CD221 directed magnetic(triple-function)cubosomes were capable of internalizing into RMS cells in an energy-independent mechanism.Helenalin-laden triple functionalized cubosomes showed limited impact on the viability of control fibroblast cells,while they induced a high degree cytotoxicity against RMS cells.Profound tumour cell death was observed in both two-dimensional(2D)culture and three-dimensional(3D)tumour spheroids.
基金supported by the National Thousand Talents Plan of Chinathe National Natural Science Foundation of China(Grant Nos.21673014 and U1766216)+1 种基金the 111 project(B17002)funded by the Ministry of Education of Chinathe Fundamental Research Funds for the Central Universities of China
文摘Proton exchange membrane fuel cells(PEMFC)have attracted much attention because of their high energy conversion efficiency,high power density and zero emission of pollutants.However,the high cost of the cathode platinum group metal(PGM)catalysts creates a barrier for the large-scale application of PEMFC.Tremendous efforts have been devoted to the development of low-cost PGM-free catalysts,especially the Fe-N-C catalysts,to replace the expensive PGM catalysts.However,the characterization methods and evaluation standards of the catalysts varies,which is not conducive to the comparison of PGM-free catalysts.U.S.Department of energy(DOE)is the only authority that specifies the testing standards and activity targets for PGM-free catalysts.In this review,the major breakthroughs of Fe-N-C catalysts are outlined with the reference of DOE standards and targets.The preparation and characteristics of these highly active Fe-N-C catalysts are briefly introduced.Moreover,the efforts on improving the mass transfer and the durability issue of Fe-N-C fuel cell are discussed.Finally,the prospective directions concerning the comprehensive evaluation of the Fe-N-C catalysts are proposed.
文摘A tracking filter algorithm based on the maneuvering detection delay is presented in order to solve the fuzzy problem of target maneuver decision introduced by the measure?ment errors of active sonar. When the maneuvering detection is unclear, two target moving hypotheses, the uniform and the maneuver, derived from the method of multiple hypothesis tracking, are generated to delay the final decision time. Then the hypothesis test statistics is constructed by using the residual sequence. The active sonar?s tracking ability of unknown prior information targets is improved due to the modified sequential probability ratio test and the integration of the advantages of strong tracking filter and the Kalman filter. Simulation results show that the algorithm is able to not only track the uniform targets accurately, but also track the maneuvering targets steadily. The effectiveness of the algorithm for real underwater acoustic targets is further verified by the sea trial data processing results.
基金funded by the Science and Technology Development Fund,Macao S.A.R(Grant No.0023/2019/A and SKLQRCM(UM)-2020-2022,China)National Key Research and Development Program of China(Grant No.2017YFE0191500)the Research Fund of the University of Macao,Macao S.A.R.(Grant No.MYRG2019-00143-ICMS,China)
文摘Inflammatory bowel disease(IBD)is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization.With no curative therapy for IBD at present,the development of effective therapeutics is highly advocated.Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention(EPR)effect caused by the inflammation.However,the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release.Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs,ligandmodified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects.This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands.Finally,challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.
文摘Binary asymmetric nanocrystals (BNCs), composed of a photoactive TiO2 nanorod joined with a superparamagnetic γ-Fe203 spherical domain, were embedded in polyethylene glycol modified phospholipid micelle and successfully bioconjugated to a suitably designed peptide containing an RGD motif. BNCs represent a relevant multifunctional nanomaterial, owing to the coexistence of two distinct domains in one particle, characterized by high photoactivity and magnetic properties, that is particularly suited for use as a phototherapy and hyperthermia agent as well as a magnetic probe in biological imaging. We selected the RGD motif in order to target integrin expressed on activated endothelial cells and several types of cancer cells. The prepared RGD-peptide/BNC conjugates, comprehensively monitored by using complementary optical and structural techniques, demon- strated a high stability and uniform dispersibility in biological media. The cytotoxicity of the RGD-peptide/BNC conjugates was studied in vitro. The cellular uptake of RGD-peptide conjugates in the cells, assessed by means of two distinct approaches, namely confocal microscopy analysis and emission spectroscopy determination in cell lysates, displayed selectivity of the RGD-peptide-BNC conjugate for the cw]33 integrin. These RGD-peptide-BNC conjugates have a high potential for theranostic treatment of cancer.
基金financially supported by the National Natural Science Foundation of China (Nos.20974062,30700175)National Basic Research Program (Nos.2009CB930400,2012CB821500)China National Funds for Distinguished Young Scientists (No.21025417)
文摘Hyperbranched polysulfonamine (HPSA) is a promising biomaterial due to its highly branched spherical architecture and efficient intracellular translocation. To realize the fianctionalization of HPSA, both N-succinimidyl 3-(2- pyridyldithio) propionate (SPDP) for tethering the human-mouse chimeric monoclonal antibody CH12 and N-hydroxy succinimidyl S-acetylmercaptoacetyltriglycinate (NHS-MAG3) for labeling 188Re were sequentially grafted onto the primary amine terminals of HPSA via covalent linkages, attaining the SPDP-HPSA-MAG3 intermediate. In order to reserve the structural integrity of CH12, the fragment crystallizable (Fc) region was also processed by oxidation of oligosaccharide moieties with sodium periodate and then reacted with N-(κ-maleimidoundecanoic acid) hydrazide (KMUH). After chelating 188Re with MAG3 group, the SPDP was reduced to PDP and connected onto the maleinimide group at the Fc region. As a result, both the epidermal growth factor receptor viii (EGFRvIII) targeted monoclonal antibody CH12 and the radionuclide 188Re were conjugated to the HPSA-based vehicles, forming the 188Re-labeled and CH12-tethered HPSA (CH12-HPSA- 188Re). The molecular weight and in vitro stability of CH12-HPSA-188Re were evaluated by gel electrophoresis and paper chromatography. On one hand, the CH12-HPSA-188Re could specifically bind to the EGFRvlII-positive human hepatocarcinoma cells in vitro. On the other hand, it could also target at the tumor tissue of nude mice in vivo. Hence, the CH12-HPSA-188Re could effectively target at the human hepatocarcinoma and facilitate the tumor detection and targeted radioimmunotherapy.
基金supported by the National Natural Science Foundation of China(Nos.12175280 and 12250610193)the National Key R&D Program of China(No.2016YFA0400500)+1 种基金the support of the CAS“Light of West China”Programthe support of the Natural Science Foundation of Gansu(No.23JRRA676)。
文摘A charged particle array named MATE-PA,which serves as an auxiliary detector system for a Multi-purpose Active-target Time projection chamber used in nuclear astrophysical and exotic beam Experiments(MATE),was constructed.The array comprised of 20 single-sided strip-silicon detectors covering approximately 10%of the solid angle.The detectors facilitated the detection of reaction-induced charged particles that penetrate the active volume of the MATE.The performance of MATE-PA has been experimentally studied using an alpha source and a 36-MeV 14 N beam injected into the MATE chamber on the radioactive ion beam line in Lanzhou(RIBLL).The chamber was filled with a gas mixture of 95%4 He and 5%CO_2 at a pressure of 500 mbar.The results indicated good separation of light-charged particles using the forward double-layer silicon detectors of MATE-PA.The energy resolution of the Si detectors was deduced to be approximately 1%(σ)for an energy loss of approximately 10 MeV caused by theαparticles.The inclusion of MATE-PA improves particle identification and increases the dynamic range of the kinetic energy of charged particles,particularly that of theαparticles,up to approximately 15 MeV.