pH-responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment

In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanopartides, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.

BIODEGRADABLE POLYMERS WITH A PHOSPHORYL-CONTAINING BACKBONE:TISSUE ENGINEERING AND CONTROLLED DRUG DELIVERY APPLICATIONS

This review provides a glimpse of the potential of the biodegradable phos-phoryl-containing polymers in medical applications. Undoubtedly these polymerspossess unique properties that are yet to be fully understood. Many areas warrantfurther investigation and much optimization remains to be done. The fascinatingchemistry of phosphorus poses interesting hurdles but at the same time leavesample room for polymer scientists to exercise their creativity in designinginteresting biomaterials. As the mutual understanding between basic and clinicalscientists on the need of medical devices and the capabilities of these newbiomaterials expands, imaginative application of new biomaterials to other medi-cal applications can be expected.

Synthesis of the Core-Shell Structure Materials as the Controlled-Release Drug Carrier

We have developed a controlled-release drug carrier. Smartly controlled-release polymer nanoparticles were firstly synthesized through RAFT polymerization as the controlled-release core. The structural and particle properties of polymer nanoparticles were characterized by nuclear magnetic resonance spectroscopy (1H-NMR), scanning electron microscope (SEM) and X-ray spectroscopy (EDX). Mesoporous materials were selected as the shell materials to encapsulate the smart core as the stable shell. The mesoporous shell was characterized by transmission electron microscopy (TEM) and scanning electron microscope (SEM). All the results showed that a well-defined core-shell structure with mesoporous structure was obtained, and this controllable delivery system will have the great potential in nanomedicine.

Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

Biointerface engineering nanoplatforms for cancer-targeted drug delivery

Over the past decade,nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy.Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and an improved prognosis.Innovative design and advanced biointerface engineering have promoted the development of various nanocarriers for optimized drug delivery.Keeping in mind the biological framework of the tumormicroenvironment,biomembrane-camouflaged nanoplatforms have been a research focus,reflecting their superiority in cancer targeting.In this review,we summarize the development of various biomimetic cell membrane-camouflaged nanoplatforms for cancertargeted drug delivery,which are classified according to the membranes fromdifferent cells.The challenges and opportunities of the advanced biointerface engineering drug delivery nanosystems in cancer therapy are discussed.

Modular Hydrogels for Drug Delivery

The development of novel drug delivery systems is an essential step toward controlled site-specific administration of therapeutics within the body. It is desirable for delivery vehicles to be introduced into the body through minimally invasive means and, these vehicles should be capable of releasing drug to their intended location at a controlled rate. Furthermore, it is desirable to develop drug delivery systems that are capable of in vivo to suffer degradation and to deliver the drug completely, avoiding the need to surgically remove the vehicle at the end of its useful lifetime. Hydrogels are of particular interest for drug delivery applications due to their ability to address these needs in addition to their good biocompatibility, tunable network structure to control the diffusion of drugs and, tunable affinity for drugs. However, hydrogels are also limited for drug delivery applications due to the often quick elution of drug from their highly swollen polymer matrices as well as the difficulty inherent in the injection of macroscopic hydrogels into the body. This paper presents an overview to the advances in hydrogels based drug delivery. Different types of hydrogels can be used for drug delivery to specific sites in the gastrointestinal tract ranging from the oral cavity to the colon. These novel systems exhibit a range of several peculiar properties which make them attractive as controlled drug release formulations. Moreover, such materials are biocompatible and can be formulated to give controlled, pulsed, and triggered drug release profiles in a variety of tissues.

Control of Surface Wrinkles on Shape Memory PLA/PPDO Micro‑nanofibers and Their Applications in Drug Release and Anti‑scarring

Micro-and nano-fibers of shape memory polymers(SMP)offer multiple advantages like high specific surface area,poros-ity,and intelligence,and are suitable for biomedical applications.In this study,biodegradable poly(p-dioxanone)(PPDO)materials were incorporated to improve the brittleness of shape memory polylactic acid(PLA),and plasticizers were used to reduce the transition temperature of SMP composites such that their transitions could be induced close to body temperature.Furthermore,an electrostatic spinning technology was applied to prepare SMP fibers with wrinkled structures and regulate their microstructures and morphologies such that the intelligent transition of wrinkled and smooth morphologies can be achieved on the fiber surface.The application of this controllable-morphology fiber membrane in intelligent controlled drug release and scar inhibition after Ahmed Glaucoma Valve(AGV)implantation was also studied.The drug release from the stretched and deformed drug-loaded fiber membranes was faster than those from membranes with the original shape.This membrane with micro-and nano-fibers had good anti-scarring effects that improved after drug loading.The achievement of intelligent controlled drug release and the evident anti-scarring effects of the membrane broaden the application of SMP fibers in the biomedical field.

Water-responsive 4D printing based on self-assembly of hydrophobic protein “Zein” for the control of degradation rate and drug release

Four-dimensional(4D)printing is a promising technology that provides solutions for compelling needs in various fields.Most of the reported 4D printed systems are based on the temporal shape transformation of printed subjects.Induction of temporal heterogenicity in functions in addition to shape may extend the scope of 4D printing.Herein,we report a 4D printing approach using plant protein(zein)gel inspired by the amyloid fibrils formation mechanism.The printing of zein gel in a specialized layered-Carbopol supporting bath with different water concentrations in an ethanol-water mixture modulates hydrophobic and hydrogen bonding that causes temporal changes in functions.The part of the construct printed in a supporting bath with higher water content exhibits higher drug loading,faster drug release and degradation than those printed in the supporting bath with lower water content.Tri-segment conduit and butterfly-shaped construct with two asymmetrical wings are printed using this system to evaluate biomedical function as nerve conduit and drug delivery system.4D printed conduits are also effective as a drug-eluting urethral stent in the porcine model.Overall,this study extends the concept of 4D printing beyond shape transformation and presents an approach of fabricating specialized baths for 4D printing that can also be extended to other materials to obtain 4D printed medical devices with translational potential.

新形势下禁毒学专业实践教学体系的改革设想

随着两个《意见》出台,公安教育训练中实践教学的地位亟待提升。公安院校公安类专业实践教学体系的改革可从校内和校外实践教学两个方面进行,做好课程教学实训、见习、综合实训、毕业实习和社会活动等五个模块的改革和探索,使禁毒学专业紧密结合禁毒实战,形成一套有特色的良性的禁毒实践教学体系。

我国近年来禽肉产品主要药物风险因素分析及控制

通过收集国家市场监督管理总局组织开展的禽肉产品监督抽检和风险监督数据,结合农业农村部畜禽产品质量安全风险评估实验室(青岛)及相关风险监测和评估单位近年来开展禽肉质量安全风险评估研究获得的风险监测数据,发现乌鸡、地方品种土鸡、鲜(冻)鸡肉、鸭肉等禽肉产品中,恩诺沙星(或以恩诺沙星+环丙沙星计)、氧氟沙星、磺胺类药物、氟苯尼考(胺)、氯霉素、尼卡巴嗪及残留标志物、阿奇霉素、多西环素、土霉素、金刚烷胺、硝基呋喃类代谢物[呋喃唑酮代谢物3-氨基-2-噁唑烷基酮(AOZ)、呋喃西林代谢物氨基脲(SEM)和呋喃它酮代谢物5-吗啉甲基-3-氨基-2-噁唑烷基酮(AMOZ)]、五氯酚酸钠等药物存在较大残留安全风险,针对这些主要风险因素分析,提出了有关控制对策建议,包括:建立相关法律法规、标准、公告等贯彻落实和强制性培训制度,加快制定我国地方品种畜禽养殖生产加工规范类标准和产品标准,建立协调合作机制、加强数据信息共享,推广农产品质量安全承诺合格证制度,加快“两品一标”畜禽产品发展。

论禁毒学专业学生侦查意识的养成

侦查意识是侦查素质构成的重要基础和必要条件。随着毒品犯罪形势日趋严峻、法律环境日趋完善、科技水平日新月异,毒品犯罪侦查工作对侦查意识提出了全新要求。禁毒学专业学生侦查意识的培养,是禁毒队伍侦查意识提升的着力点。应当结合当前禁毒学专业学生教育的现状,明确侦查意识培养的核心内容,努力培养学生的侦查意识。

我国近年来禽蛋产品主要药物风险因素分析及控制

通过收集近年来国家市场监督管理总局发布的禽蛋产品监督抽检的监测数据,结合国内有关畜禽产品质量安全检测评估机构开展禽蛋产品检测研究获得的数据,发现鲜鸡蛋、土鸡蛋、乌鸡蛋、鹅蛋等禽蛋产品中,氟苯尼考(胺)、恩诺沙星(以恩诺沙星与环丙沙星之和计)、氧氟沙星、甲砜霉素、氯霉素、磺胺类药物(总量)、甲氧苄啶、甲硝唑、地美硝唑、多西环素、呋喃唑酮代谢物[3-氨基-2-噁唑烷基酮(AOZ)]、金刚烷胺等药物存在残留安全风险。针对这些主要药物风险因素进行分析,提出有关控制对策建议:加强对国家法律、法规、公告的宣贯和培训;倡导建立集约化、标准化的蛋禽养殖场;建立蛋禽场良好生物安全体系,落实《全国兽用抗菌药使用减量化行动方案》;增强禽蛋产品生产主体的责任意识,切实落实好食用农产品承诺达标合格证制度;加强对养禽过程中药物使用的监管,强化养殖环节的监督检查和产品抽检;建立禽蛋产品跨省、跨地区流通监管机制,强化禽蛋产品市场准入和市场流通监管等。

基于社会实践的禁毒专业人才培养模式探索——以四川警察学院禁毒专业为例

开展社会实践教学是公安院校禁毒专业的人才培养方案的重要组成部分,符合当前公安工作实际和公安队伍建设的需求。总体而言,公安院校禁毒专业社会实践教学取得了一定成效,但还存一些不足。四川警察学院禁毒专业为不断深化毒专业社会实践教学,以优化社会实践教学改革作为背景,研究禁毒专业人才需求现状,探讨禁毒社会实践教学工作者和学生应具备的能力和素质,完善专业培养方案,革新社会实践教学路径、方法和手段,建构科学系统的公安专业人才实践教学体系,取得了有益的探索效果。进一步深化的思路是:将社会实践内容编入禁毒专业实战化教学大纲;通过校局合作拓展社会实践广度和宽度;将"大思政"内容融入社会实践教学环节。

Progress on intelligent hydrogels based on RAFT polymerization:Design strategy, fabrication and the applications for controlled drug delivery

Although intelligent hydrogels have shown bright potential application in biomedical fields,they were prepared by conventional methods and still face many serious challenges,such as uncontrollable stimulus-response and low response sensitivity.Recently,RAFT polymerization provides a versatile strategy for the fabrication of intelligent hydrogels with improved stimulus-response properties,owing to the ability to efficiently construct hydrogel precursors with well-defined structure,such as block copolymer,graft copolymer,star copolymer.In this review,we summarized the recent progress on intelligent hydrogels based on RAFT polymerization with emphasis on their fabrication strategies and applications for controlled drug delivery.

Poly(β-cyclodextrin)-mediated Polylactide-cholesterol Stereocomplex Micelles for Controlled Drug Delivery

A series of host-guest interaction-adjusted polylactide stereocomplex micelles was prepared via the self-assembly of 4-armed poly（ethylene glycol）-block-poly（L-lactide/D-lactide）-cholesterol （4-armed PEG-b-PLLA/PDLA-CHOL） and poly（β-cyclodextrin） （PCD） with the molar ratios of CHOL/β-CD at 1：0.5, 1 ：l, and 1：2 in an aqueous environment. The hydrodynamic diameters of the micelles ranged from 84.1 nm to 107 nm depending on the molar ratio of CHOL/β-CD. It was shown that the micelle with the largest proportion of PCD possessed excellent abilities in drug release, cell internalization as well as proliferation inhibitory effect toward human A549 lung cancer cells. The results demonstrated that the stereocomplex and host-guest interactions-mediated PLA micelles exhibited great potential in sustained drug delivery.

Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior

The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system.In this study,two kind of aqueous model drugs with different molecule weight,Congo red and albumin from bovine serum(BSA)were nanoencapsulated in poly(DL-lactic-co-glycolic acid)(PLGA)microspheres by emulsion electrospray.In the preparation process,the aqueous phase of drugs was added into the PLGA chloroform solution to form the emulsion solution.The emulsion was then electrosprayed to fabricate drugnanoencapsulated PLGA microspheres.The morphology of the PLGA microspheres was affected by the volume ratio of aqueous drug phase and organic PLGA phase(V_(w)/V_(o))and the molecule weight of model drugs.Confocal laser scanning microcopy showed the nanodroplets of drug phase were scattered in the PLGA microspheres homogenously with different distribution patterns related to V_(w)/V_(o).With the increase of the volume ratio of aqueous drug phase,the number of nanodroplets increased forming continuous phase gradually that could accelerate drug release rate.Moreover,BSA showed a slower release rate from PLGA microspheres comparing to Congo red,which indicated the drug release rate could be affected by not only V_(w)/V_(o)but also the molecule weight of model drug.In brief,the PLGA microspheres prepared using emulsion electrospray provided an efficient and simple systemto achieve controlled drug release at a desired rate satisfying the need of the practices.

In situ-prepared homogeneous supramolecular organic framework drug delivery systems(sof-DDSs)：Overcoming cancer multidrug resistance and controlled release

Water-soluble three-dimensional porous supramolecular organic frameworks（SOFs） have been demonstrated as a new generation of homogeneous polycationic platforms for anti-cancer drug delivery.The new SOF drug delivery systems（sof-DDSs） can adsorb dianionic pemetrexed（PMX）,a clinically used chemotherapeutic agent instantaneously upon dissolving in water,which is driven by both electrostatic attraction and hydrophobicity.The in situ-prepared PMX@SOFs are highly stable and can avoid important release of the drug during plasm circulation and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells to enter the cancer cells.Acidic microenvironment of cancer cells promotes the release of the drug in cancer cells.Both in vitro and in vivo studies have revealed that sofDDSs considerably improve the treatment efficacy of PMX,leading to 6-12-fold reduction of the IC50 values,as compared with that of PMX alone.The new drug delivery strategy omits the loading process required by most of reported nanoparticle-based delivery systems and thus holds promise for future development of low-cost drug delivery systems

In situ synthesis of gold nanostars within liposomes for controlled drug release and photoacoustic imaging

This report describes the design and synthesis of gold nanostars(AuNSs) containing liposomes by the in situ reduction of gold precursor,HAuCU(pre-encapsulated within the liposomes) through HEPES diffusion and reduction.Compared with the conventional process that encapsulates the pre-synthesized gold nanoparticles into liposomes during the thin-film hydration step,this facile and convenient method allows the formation and simultaneous encapsulation of AuNSs within liposomes.The absorption spectra of AuNSs can be tuned between visible and near infra-red(NIR) regions by controlling the size and morphology of AuNSs through varying the concentrations of HAuCU and HEPES.As a proof of concept,we demonstrate the synthesis of AuNSs with a maximum absorbance at 803 nm within the temperature-sensitive liposomes.These liposomes can produce stronger photoacoustic signals(1.5 fold) in the NIR region than blood.Furthermore,when there are drugs(i.e.,doxorubicin) within these liposomes,the irradiation with the NIR pulse laser will disrupt the liposomes and trigger the 100%release of these pre-encapsulated drugs within 10 seconds.In comparison,there is neglectable contrast enhancement or minor release(10%) of drugs for the pure liposomes under the same conditions.Finally,cell experiment shows the potential therapeutic application of this system.

Amphiphilic poly(ethylene glycol)-b-poly(ethylene brassylate)copolymers: One-pot synthesis, self-assembly, and controlled drug release

A set of amphiphilic poly（ethylene glycol）-b-poly（ethylene brassylate）（PEG-b-PEB） copolymers based on the PEB hydrophobic block was first synthesized by ring-opening polymerization of ethylene brassylate with an organic catalyst. The EB/PEG molar ratios and reaction times were adjusted to achieve different chain lengths of PEB. Block copolymers that were characterized by1 H NMR and GPC could selfassemble into multimorphological aggregates in aqueous solution, which were characterized by DLS and TEM. The hydrophobic doxorubicin（DOX） was chosen as a drug model and successfully encapsulated into the nanoparticles. The release kinetics of DOX were investigated.

Self-assembled Nanoparticles based on Folic Acid Modifi ed Carboxymethyl Chitosan Conjugated with Targeting Antibody

Nanoparticles conjugated with antibody were designed as active drug delivery system to reduce the toxicity and side effects of drugs for acute myeloid leukemia（AML）.Moreover,methotrexate（MTX）was chosen as modeldrug and encapsulate within folic acid modified carboxymethylchitosan（FACMCS）nanoparticles through self-assembling.The chemicalstructure,morphology,release and targeting of nanoparticles were characterized by routine detection.It is demonstrated that the mean diameter is about 150 nm,the release rate increases with the decreasing of p H,the binding rate of CD33 antibody and FA-CMCS nanoparticles is about 5：2,and nanoparticles can effectively bind onto HL60 cells in vitro.The experimentalresults indicate that the FA-CMCS nanoparticles conjugated with antibody may be used as a potentialp Hsensitive drug delivery system with leukemic targeting properties.