Repurposing drugs for solid tumor treatment:focus on immune checkpoint inhibitors

Cancer remains a significant global health challenge with limited treatment options beyond systemic therapies,such as chemotherapy,radiotherapy,and molecular targeted therapy.Immunotherapy has emerged as a promising therapeutic modality but the efficacy has plateaued,which therefore provides limited benefits to patients with cancer.Identification of more effective approaches to improve patient outcomes and extend survival are urgently needed.Drug repurposing has emerged as an attractive strategy for drug development and has recently garnered considerable interest.This review comprehensively analyses the efficacy of various repurposed drugs,such as transforming growth factor-beta(TGF-β)inhibitors,metformin,receptor activator of nuclear factor-κB ligand(RANKL)inhibitors,granulocyte macrophage colony-stimulating factor(GM-CSF),thymosinα1(Tα1),aspirin,and bisphosphonate,in tumorigenesis with a specific focus on their impact on tumor immunology and immunotherapy.Additionally,we present a concise overview of the current preclinical and clinical studies investigating the potential therapeutic synergies achieved by combining these agents with immune checkpoint inhibitors.

Combined effects of Cantide and chemotherapeutic drugs on inhibition of tumor cells' growth in vitro and in vivo

AIM: To investigate the combination effect of hTERT antisense oligonucleotide 'Cantide' and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation of HepG2, BGC and A549 cell lines in vitro, and to investigate the efficacy of Cantide used in combination with cisplatin (DDP) in vivo.METHODS: Cantide was transfected into these tumor cells by Lipofectin, and cell growth activity was calculated by microcytotoxicity assay. In vivo study, cells of HepG2 were implanted in Balb/c nude mice for 4 d. Then Cantide, DDP and Cantide+DDP were given intraperitoneally for 24 d respectively. The body weights of the tumor-bearing animals and their tumor mass were measured later to assess the effect of combination therapy in the nude mice.To evaluate the interaction of Cantide and these chemotherapeutic drugs, SAS software and Jin Zhengjun method were used.RESULTS: Combination treatments with 0.1 μmol/L Cantide reduced the IC50 of DDP, 5-FU and ADM from 1.07, 4.15and 0.29 μg/mL to 0.25, 1.52 and 0.12 μg/mL respectively.The inhibition ability of DDP, 5-FU and ADM respectively in combination with Cantide in these tumor cells was higher than that of these drugs alone (P＜0.0001). And synergism (Q≥1.15) was observed at the lower concentration of DDP (≤1 μg/mL), 5-FU (≤10 μg/mL) and ADM (≤0.1 μg/mL)with combination of Cantide. In vivo, combination treatment with Cantide and DDP produced the greater growth inhibition of human liver carcinoma cells HepG2 in nude mice (0.65±0.19 g tumor) compared with that when only one of these drugs was used (Cantide group: 1.05±0.16 g tumor, P= 0.0009＜0.001; DDP group: 1.13±0.09 g tumor,P= 0.0001＜0.001).CONCLUSION: These findings indicate that Cantide may enhance therapeutic effectiveness of chemotherapeutic drugs over a wide range of tumor cells in vitro, and the combination use of Cantide and DDP can produce much higher inhibition rates, as compared with when either of these drugs was used only in vivo.

3D bioprinting of in vitro porous hepatoma models:establishment,evaluation,and anticancer drug testing

Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study describes the use of threedimensional(3D)bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells(3DP-7721)by combining gelatin methacrylate(GelMA)and poly(ethylene oxide)(PEO)as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of cells.The GelMA(10%,mass fraction)and PEO(1.6%,mass fraction)hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,satisfactorymechanical properties,and biocompatibility for the creation of the 3DP-7721 model.Immunofluorescence analysis and quantitative real-time fluorescence polymerase chain reaction(PCR)were used to evaluate the biological properties of the model.Compared with the two-dimensional culture cell model(2D-7721)and the 3D mixed culture cell model(3DM-7721),3DP-7721 significantly improved the proliferation of cells and expression of tumor-related proteins and genes.Moreover,we evaluated the differences between the three culture models and the effectiveness of antitumor drugs in the three models and discovered that the efficacy of antitumor drugs varied because of significant differences in resistance proteins and genes between the three models.In addition,the comparison of tumor formation in the three models found that the cells cultured by the 3DP-7721 model had strong tumorigenicity in nude mice.Immunohistochemical evaluation of the levels of biochemical indicators related to the formation of solid tumors showed that the 3DP-7721 model group exhibited pathological characteristics of malignant tumors,the generated solid tumors were similar to actual tumors,and the deterioration was higher.This research therefore acts as a foundation for the application of 3DP-7721 models in drug development research.

Visualization analysis of research hotspots and trends on gastrointestinal tumor organoids

BACKGROUND Gastrointestinal tumor organoids serve as an effective model for simulating cancer in vitro and have been applied in basic biology and preclinical research.Despite over a decade of development and increasing research achievements in this field,a systematic and comprehensive analysis of the research hotspots and future trends is lacking.AIM To address this problem by employing bibliometric tools to explore the publication years,countries/regions,institutions,journals,authors,keywords,and references in this field.METHODS The literature was collected from Web of Science databases.CiteSpace-6.2R4,a widely used bibliometric analysis software package,was used for institutional analysis and reference burst analysis.VOSviewer 1.6.19 was used for journal cocitation analysis,author co-authorship and co-citation analysis.The‘online platform for bibliometric analysis(https://bibliometric.com/app)’was used to assess the total number of publications and the cooperation relationships between countries.Finally,we employed the bibliometric R software package(version R.4.3.1)in R-studio,for a comprehensive scientific analysis of the literature.RESULTS Our analysis included a total of 1466 publications,revealing a significant yearly increase in articles on the study of gastrointestinal tumor organoids.The United States(n=393)and Helmholtz Association(n=93)have emerged as the leading countries and institutions,respectively,in this field,with Hans Clevers and Toshiro Sato being the most contributing authors.The most influential journal in this field is Gastroenterology.The most impactful reference is"Long term expansion of epithelial organs from human colon,adenoma,adenocarcinoma,and Barrett's epithelium".Keywords analysis and citation burst analysis indicate that precision medicine,disease modeling,drug development and screening,and regenerative medicine are the most cutting-edge directions.These focal points were further detailed based on the literature.CONCLUSION This bibliometric study offers an objective and quantitative analysis of the research in this field,which can be considered as an important guide for next scientific research.

Systemic therapy in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.

Blood glucose changes surrounding initiation of tumor-necrosis factor inhibitors and conventional disease-modifying anti-rheumatic drugs in veterans with rheumatoid arthritis

AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.

A pH-responsive nanoparticle delivery system containing dihydralazine and doxorubicin-based prodrug for enhancing antitumor efficacy

The efficacy of nanoparticle(NP)-based drug delivery technology is hampered by aberrant tumor stromal microenvironments(TSMs)that hinder NP transportation.Therefore,the promotion of NP permeation into deep tumor sites via the regulation of tumor microenvironments is of critical importance.Herein,we propose a potential solution using a dihydralazine(HDZ)-loaded nanoparticle drug delivery system containing a pH-responsive,cyclic RGD peptide-modified prodrug based on doxorubicin(cRGD-Dex-DOX).With a combined experimental and theoretical approach,we find that the designed NP system can recognize the acid tumor environments and precisely release the encapsulated HDZ into tumor tissues.HDZ can notably downregulate the expression levels of hypoxia-inducible factor 1α(HIF1α),α-smooth muscle actin,and fibronectin through the dilation of tumor blood vessels.These changes in the TSMs enhance the enrichment and penetration of NPs and also unexpectedly promote the infiltration of activated T cells into tumors,suggesting that such a system may offer an effective“multifunctional therapy”through both improving the chemotherapeutic effect and enhancing the immune response to tumors.In vivo experiments on 4T1 breast cancer bearing mice indeed validate that this therapy has the most outstanding antitumor effects over all the other tested control regimens,with the lowest side effects as well.

The promises and challenges of patient-derived tumor organoids in drug development and precision oncology

In the era of precision medicine,cancer researchers and oncologists are eagerly searching for more realistic,cost effective,and timely tumor models to aid drug development and precision oncology.Tumor models that can faithfully recapitulate the histological and molecular characteristics of various human tumors will be extremely valuable in increasing the successful rate of oncology drug development and discovering the most efficacious treatment regimen for cancer patients.Two‐dimensional(2D)cultured cancer cell lines,genetically engineered mouse tumor(GEMT)models,and patient‐derived tumor xenograft(PDTX)models have been widely used to investigate the biology of various types of cancers and test the efficacy of oncology drug candidates.However,due to either the failure to faithfully recapitulate the complexity of patient tumors in the case of 2D cultured cancer cells,or high cost and untimely for drug screening and testing in the case of GEMT and PDTX,new tumor models are urgently needed.The recently developed patient‐derived tumor organoids(PDTO)offer great potentials in uncovering novel biology of cancer development,accelerating the discovery of oncology drugs,and individualizing the treatment of cancers.In this review,we will summarize the recent progress in utilizing PDTO for oncology drug discovery.In addition,we will discuss the potentials and limitations of the current PDTO tumor models.

Down-regulation of Hsp90 could change cell cycle distribution and increase drug sensitivity of tumor cells

:AIM To construct Hsp90 antisense RNAeukaryotic expression vector, transfect it intoSGC7901 and SGC7901/VCR of MDR-type humangastric cancer cell lines, HCC7402 of humanhepatic cancer and Eel09 of human esophagealcancer cell lines, and to study the cell cycledistribution of the gene transected cells andtheir response to chemotherapeutic drugs.METHODS A I .03kb cDNA sequence of Hsp90Pwas obtained from the primary plasmid phHsp90by EcoR 1 and BamH I nuclease digestion andwas cloned to the EcoR 1 and BamH 1 site ofthe pcDNA by T4DNA ligase and an antisenseorientation of Hsp900 expression vector wasconstructed. The constructs were transfectedwith lipofectamine and positive clones wereselected with G418. The expression of RNA wasdetermined with dot blotting and RNaseprotection assay, and the expression of Hsp90protein determined with Western blot. Cell cycledistribution of the transfectants was analyzedwith flow cytometry, and the drug sensitivity ofthe transfectants to adriamycin (ADR ),vincrinstine (VCR ), mitomycin (MMC ) andcyclophosphamide (CTX ) with MTT andintracellular drug concentration of thetransfectants was determined with flowcytometry.RESULTS In EcoR 1 and BamH I restrictionanalysis, the size and the direction of the clonedsequence of Hsp900 remained what had beendesigned and the gene constructs were namedpcDNA-Hsp90. AH^SGC7901, AH^SGC7901/ VCR,AH-HCC7402 and AH-Eel09 cell clones allexpressed Hsp90 anti--sense RNA. Theexpression of Hsp90 was down--regulated in AHSGC7901, AH--SGC7901/ VCR, AH-HCC7402 andAH--Eel09 cell clones. Cell cycle distribution waschanged differently. In AH-SGC7901/ VCR andAH-Ec109 cells, G, phase cells were increased; Sphase and G, phase cells were decreased ascompared with their parental cell lines. In AHSGC7901 cell, G, phase cells were decreased, Qphase cells increased and S phase cells were notchanged, and in AH-HCC7402 cells G,, S and qphase cells remained unchanged as comparedwith their parental cell lines. The sensitivity ofAH--SGC7901, AH--SGC7901/ VCR, AH-HCC7402 andAH-Ec109 to chemotherapeutic drugs, thesensitivity ot AH--SGC7901/ VCR to ADR, VCR,MMC and CTX the sensitivity of AH-HCC7402 toADR and VCR, and the sensitivity of Eel09 toADR, VCR and CTX all increased as comparedwith their parental cell lines. The meanfluorescence intensity of ADR in AH--SGC7901,AH-SGC7901/ VCR, AH--HCC7402 and AH-Ec109was also significantly elevated (P< 0. 05).CONCLUSION Down-regulation of HsP90 couldchange cell cycle distribution and increase thedrug sensitivity of tumor cells.

Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors

Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment.This study was aiming to investigate the potential of concurrent delivery of resveratrol(RES)and docetaxel(DTX)via polymeric nanocarriers to treat breast cancer.To this end,methoxyl poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PDLA)was prepared and characterized using FTIR and 1H NMR,and their molecular weights were determined by GPC.Isobologram analysis and combination index calculation were performed to find the optimal ratio between RES and DTX to against human breast adenocarcinoma cell line(MCF-7 cells).Subsequently,RES and DTX were loaded in the mPEG-PDLA micelles simultaneously,and the morphology,particle size distribution,in vitro release,pharmacokinetic profiles,as well as cytotoxicity to the MCF-7 cells were characterized.IC50 of RES and DTX in MCF-7 cells were determined to be 23.0μg/ml and 10.4μg/ml,respectively,while a lower IC50 of 4.8μg/ml of the combination of RES and DTX was obtained.The combination of RES and DTX at a ratio of 1:1(w/w)generated stronger synergistic effect than other ratios in the MCF-7 cells.RES and DTX loaded mPEG-PDLA micelles exhibited prolonged release profiles,and enhanced cytotoxicity in vitro against MCF-7 cells.The AUC(0→t)of DTX and RES in mPEG-PDLA micelles after i.v.administration to rats were 3.0-fold and 1.6-fold higher than that of i.v.injections of the individual drugs.These findings indicated that the co-delivery of RES and DTX using mPEG-PDLA micelles could have better treatment of tumors.

Analysis of Pathogen Distribution and Drug Resistance of Nosocomial Infections Accompanied in Patients with Malignant Tumor

Objective： To investigate the pathogen distribution and drug resistance of nosocomial infections accompanied in patients with malignant tumor. Methods： The pathogen culture and drug-sensitivity data of 107 specimens isolated from malignant tumor patients accompanied with nosocomial infection were retrospectively analyzed. Results： Among 118 strains of pathogens isolated from 107 specimens, 77 were gram-negative bacillus（65.3%）, 26 were gram-positive coccus（65.3%）, and 15 were fungus（12.7%）. Eleven specimens were revealed to have combined infection of bacterium and fungus. Gram-negative bacillus showed high sensitivity to amikacin, ciprofloxacin, and tienam. Gram-positive cocci were highly sensitive to tienam and vancomycin. The bacteria were resistant to other antibiotics in different degrees, Vancomycin-resistant staphylococcus was not detected, Candida was sensitive to antifungals. Conclusion： Conditional pathogenic bacteria were mainly responsible for nosocomial infections in malignant tumor patients with considerable drug resistance. This shows that bacterial tests and the rational use of antibiotics should be emphasized in clinical practice to prevent the formation of drug resistant strains and further endogenous infections.

Functionalized magnetic nanoparticles for drug delivery in tumor therapy

The side effects of chemotherapy are mainly the poor control of drug release. Magnetic nanoparticles(MNPs) have super-paramagnetic behaviors which are preferred for biomedical applications such as in targeted drug delivery, besides, in magnetic recording, catalysis, and others. MNPs, due to high magnetization response, can be manipulated by the external magnetic fields to penetrate directly into the tumor, thus they can act as ideal drug carriers. MNPs also play a crucial role in drug delivery system because of their high surface-to-volume ratio and porosity. The drug delivery in tumor therapy is related to the sizes, shapes, and surface coatings of MNPs as carriers. Therefore, in this review, we first summarize the effects of the sizes, shapes, and surface coatings of MNPs on drug delivery, then discuss three types of drug release systems, i.e., p H-controlled, temperature-controlled, and magnetic-controlled drug release systems, and finally compare the principle of passive drug release with that of active drug release in tumor therapy.

Aqueous Self-Assembly of Block Copolymers to Form Manganese Oxide-Based Polymeric Vesicles for Tumor Microenvironment-Activated Drug Delivery

Molecular self-assembly is crucially fundamental to nature.However,the aqueous self-assembly of polymers is still a challenge.To achieve self-assembly of block copolymers [(polyacrylic acid-block-polyethylene glycol-block-polyacrylic acid(PAA68-b-PEG86-b-PAA68)] in an aqueous phase,manganese oxide(MnO2) is first generated to drive phase separation of the PAA block to form the PAA68-b-PEG68-b-PAA68/MnO2 polymeric assembly that exhibits a stable structure in a physiological medium.The polymeric assembly exhibits vesicular morphology with a diameter of approximately 30 nm and high doxorubicin(DOX) loading capacity of approximately 94%.The transformation from MnO2 to Mn2+caused by endogenous glutathione(GSH)facilitates the disassembly of PAA68-b-PEG68-b-PAA68/MnO2 to enable its drug delivery at the tumor sites.The toxicity of DOXloaded PAA68-b-PEG68-b-PAA69/MnO2 to tumor cells has been verified in vitro and in vivo.Notably,drug-loaded polymeric vesicles have been demonstrated,especially in in vivo studies,to overcome the cardiotoxicity of DOX.We expect this work to encourage the potential application of polymer self-assembly.

Combination therapy in cancer:effects of angiogenesis inhibitors on drug pharmacokinetics and pharmacodynamics

Validated preclinical studies have provided evidence that anti-vascular endothelial growth factor(VEGF) compounds enhance the activity of subsequent antitumor therapy, but the mechanism of this potentiation is far from clear. The most widespread explanation is enhanced delivery of therapeutics due to vascular remodeling, lower interstitial pressure, and increased blood flow. While the antiangiogenic efects on vascular morphology have been fairly consistent in both preclinical and clinical settings, the improvement of tumor vessel function is debated. This review focuses on the efect of anti-VEGF therapy on tumor microenvironment morphology and functions, and its therapeutic beneits when combined with other therapies. The uptake and spatial distribution of chemotherapeutic agents into the tumor after anti-VEGF are examined.

Bioprinting of novel 3D tumor array chip for drug screening

Biomedical field has been seeking a feasible standard drug screening system consisting of 3D tumor model array for drug researching due to providing sufficient samples and simulating actual in vivo tumor growth situation,which is still a challenge to rapidly and uniformly establish though.Here,we propose a novel drug screening system,namely 3D tumor array chip with“layer cake”structure,for drug screening.Accurate gelatin methacryloyl hydrogel droplets(~0.1μL)containing tumor cells can be automatically deposited on demand with electrohydrodynamic 3D printing.Transparent conductive membrane is introduced as a chip basement for preventing charges accumulation during fabricating and convenient observing during screening.Culturing chambers formed by stainless steel and silicon interlayer is convenient to be assembled and recycled.As this chip is compatible with the existing 96-well culturing plate,the drug screening protocols could keep the same as convention.Important properties of this chip,namely printing stability,customizability,accuracy,microenvironment,tumor functionalization,are detailly examined.As a demonstration,it is applied for screening of epirubicin and paclitaxel with breast tumor cells to confirm the compatibility of the proposed screening system with the traditional screening methods.We believe this chip will potentially play a significant role in drug evaluation in the future.

Functional Activity of Circulating Phagocytes as Potential Pretreatment Marker of Tumor Drug Resistance

The aim of this work was a study of the functional activity of neutrophils and peripheral blood monocytes in rats with the transplanted Walker carcinosarcoma as potential predictors of the sensitivity of this tumor to doxorubicin treatment. This study provides an evidence that such indices of the functional activity of circulating phagocytes of the tumor-bearing rats as the quantity and the phagocytosis intensity of monocytes, as well as the intensity of ROS production by monocytes and neutrophils, may reflect the degree of sensitivity of the tumor to doxorubicin. So it was shown that the growth of the resistant tumor caused a significant increase of the number of circulating phagocytic cells and the intensity of phagocytosis by more than 100% (p < 0.001) compared with the corresponding indices of intact rats and rats with the parental variant of the tumor. The ability of blood mono-cytes and neutrophils of rats with a resistant tumor to produce ROS was also significantly different from that in intact rats and animals with the parental carcinosarcoma variant. The predictive value of these indices is especially important in the dynamic monitoring of the development of tumor drug resistance during long-term cancer chemotherapy. Considering the standard 2 - 3 week interval between the courses of cancer therapy and the short lifetime of circulating phagocytes, an assessment of the indices of their functional activity before each subsequent course can be considered as a pretreatment assessment. Meanwhile, further studies are needed to determine the spectrum of malignant neoplasms for which the degree of tumor drug resistance correlates with the functional activity of circulating phagocytes.

An investigation into the occupational protection status of clinical nursing staff exposed to anti-tumor drugs

Objective:To investigate the occupational protection status of clinical nursing staff vocationally exposed to anti-tumor drugs.Methods:A self-designed questionnaire was used to survey 180 clinical nursing staff vocationally exposed to anti-tumor drugs.Results:Recognition of the need for protection and dependent occupational protection behaviors were very poor in clinical nursing staff vocationally exposed to anti-tumor drugs.The management of the occupational protection of clinical nursing staff vocationally exposed to anti-tumor drugs was also seriously underdeveloped.Conclusion:There is deficiency in the understanding and related protection practices of clinical nursing staff vocationally exposed to anti-tumor drugs in our hospital.The protection measures currently employed in medical practice are inadequate in virtually every aspect considered.It is recommended that all clinical nursing staff should receive full occupational protection training in these matters.The training must raise nursing staff's awareness of the need for occupational protection and standardize their occupational protection behaviors to conform to "best practice" models.These "best practice" models should be quickly established and all staff made cognizant of them forthwith.In addition,where occupational protection systems are already in place,they should be improved to come into line with the new "best practice" models instigated.

A multi-functional nanoplatform for efficacy tumor theranostic applications

Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water soluble MoS2 nanosystem(MoS2-PEG) was synthesized and explored in drug delivery, photothermal therapy(PTT) and X-ray imaging.Doxorubicin(DOX) was loaded onto MoS2-PEG with a high drug loading efficiency(~69%)and obtained a multifunctional drug delivery system(MoS2-PEG/DOX). As the drug delivery, MoS2-PEG/DOX could efficiently cross the cell membranes, and escape from the endosome via NIR light irradiation, lead to more apoptosis in MCF-7 cells, and afford higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 11.6-fold higher DTX uptake of tumor than DOX. Besides, MoS2-PEG/DOX not only served as a drug delivery system, but also as a powerful PTT agent for thermal ablation of tumor and a strong X-ray contrast agent for tumor diagnosis. In the in vitro and in vivo studies, MoS2-PEG/DOX exhibited excellent tumor-targeting efficacy, outstanding synergistic anti-cancer effect of photothermal and chemotherapy and X-ray imaging property,demonstrating that MoS2-PEG/DOX had a great potential for simultaneous diagnosis and photothermal-chemotherapy in cancer treatment.

Recent advances in lymphatic targeted drug delivery system for tumor metastasis

The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.

Perspectives on bone-targeted nano-drug carriers for bone tumor treatment

Bone tumour is one of most common primary cancer which exhibits cancerous osteoblastic differentiation and malignant osteoid in patients.At present,chemotherapy(pre-and post-operative)is used as a standard treatment protocol for bone tumour.However,drugs used in the treatment of bone tumour induce high toxicity to normal tissues including anaemia,neutropenia,thrombocytopenia,and heart damage which further reduce the survival rate of patients.Therefore,there is an urgent need to develop a new therapeutic approach for the treatment such that it induce maximum cell killing effect in tumor cells while sparing the healthy bone cells.In this article,some new perspectives were provided on the development of bone-targeted nano-drug carriers for bone cancer treatment.We hope such discussions wouldencourage more detailed and careful studies to support product development of bone-targeted drug carriers for bone cancer treatment.