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Dynamic micelles with detachable PEGylation at tumoral extracellular pH for enhanced chemotherapy

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Asian Journal of Pharmaceutical Sciences 2020年第6期15卷 728-738页

作者： Guoqing Yan Panpan Zhang Jun Wang Xin Wang Rupei Tang engineering research centerfor Biomedical Materials School of Life ScienceAnhui UniversityHefei 230601China

Although surface PEGylation of nanomedicines can decrease serum protein adsorption in vivo,it also blocks uptake by tumor *** dilemma could be overcome by employing detachably PEGylated strategy at tumoral extracellular microenvironment to achieve improved cellular uptake while prolonged circulation ***,the amphiphilic graft copolymers with p H-sensitive ortho ester-linked m PEG in side chains and polyurethanes in backbone,can self-assemble into the free and doxorubicin(DOX)-loaded *** p H-sensitive micelles could undergo several characteristics as follows:(i)PEGylated shells for stability in sodium dodecyl sulfonate(SDS)solution;(ii)De PEGylation via degradation of ortho ester linkages at tumoral extracellular pH(6.5)for gradually dynamic size changes and effective release of DOX;and(iii)enhanced cellular uptake and cytotoxicity via positive ***,the dynamic micelles with detachable PEGylation could quickly penetrate the centers of SH-SY5 Y multicellular spheroids(MCs)and strongly inhibit tumor growth in vitro and in vivo,and might be considered as promising and effective drug carriers in tumor therapy.

关键词： Micelles Ortho ester PEGylation Size transition Antitumor

Control of the interparticle spacing in superparamagnetic iron oxide nanoparticle clusters by surface ligand engineering

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Chinese Physics B 2016年第7期25卷 427-434页

作者：王丹林兵兵申太鹏吴君豪富华夏春潮龚启勇唐惠儒宋彬艾华 national engineering research Center for biomaterials Sichuan University Wuhan Institute of Physics and Mathematics Chinese Academy of Sciences Department of Radiology West China Hospital Sichuan University

Polymer-mediated self-assembly of superparamagnetic iron oxide（SPIO） nanoparticles allows modulation of the structure of SPIO nanocrystal cluster and their magnetic properties. In this study, dopamine-functionalized polyesters（DApolyester） were used to directly control the magnetic nanoparticle spacing and its effect on magnetic resonance relaxation properties of these clusters was investigated. Monodisperse SPIO nanocrystals with different surface coating materials（poly（ε-caprolactone）, poly（lactic acid）） of different molecular weights containing dopamine（DA） structure（DA-PCL2k,DA-PCL1k, DA-PLA1k）） were prepared via ligand exchange reaction, and these nanocrystals were encapsulated inside amphiphilic polymer micelles to modulate the SPIO nanocrystal interparticle spacing. Small-angle x-ray scattering（SAXS）was applied to quantify the interparticle spacing of SPIO clusters. The results demonstrated that the tailored magnetic nanoparticle clusters featured controllable interparticle spacing providing directly by the different surface coating of SPIO nanocrystals. Systematic modulation of SPIO nanocrystal interparticle spacing can regulate the saturation magnetization（Ms） and T2 relaxation of the aggregation, and lead to increased magnetic resonance（MR） relaxation properties with decreased interparticle spacing.

关键词： nanoparticle clusters interparticle spacing ligand exchange magnetization

Platelet Membrane-Coated Nanocarriers Targeting Plaques to Deliver Anti-CD47 Antibody for Atherosclerotic Therapy

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research 2022年第3期2022卷 1-12页

作者： Liang Chen Zhongyi Zhou Cheng Hu Manfred F.Maitz Li Yang Rifang Luo Yunbing Wang national engineering research Center for biomaterials Sichuan UniversityChengdu 610065China Max Bergmann Center of biomaterials Leibniz Institute of Polymer Research DresdenDresden 01069Germany Key Lab.for Advanced Technologies of Materials Ministry of EducationSchool of Material Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Atherosclerosis,the principle cause of cardiovascular disease(CVD)worldwide,is mainly characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular *** is associated with the upregulation of CD47,a key antiphagocytic molecule that is known to render malignant cells resistant to programmed cell removal,or“efferocytosis.”Here,we have developed platelet membrane-coated mesoporous silicon nanoparticles(PMSN)as a drug delivery system to target atherosclerotic plaques with the delivery of an anti-CD47 ***,the cell membrane coat prolonged the circulation of the particles by evading the immune recognition and provided an afinity to plaques and atherosclerotic *** anti-CD47 antibody then normalized the clearance of diseased vascular tissue and further ameliorated atherosclerosis by blocking *** an atherosclerosis model established in ApoE^(-/-)mice,PMSN encapsulating anti-CD47 antibody delivery significantly promoted the efferocytosis of necrotic cells in *** the necrotic cells greatly reduced the atherosclerotic plaque area and stabilized the plaques reducing the risk of plaque rupture and advanced ***,this study demonstrated the therapeutic advantages of PMSN encapsulating anti-CD47 antibodies for atherosclerosis therapy,which holds considerable promise as a new targeted drug delivery platform for efficient therapy of atherosclerosis。

关键词： CD47 Antibody holds

Regulation effect of osteoblasts towards osteocytes by silk fibroin encapsulation

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Frontiers of Materials Science 2022年第4期16卷 1-13页

作者： Dandan LUO Rui ZHANG Shibo WANG M.Zubair IQBAL Ruibo ZHAO Xiangdong KONG Institute of Smart Biomedical Materials School of Materials Science and EngineeringZhejiang Sci-Tech UniversityHangzhou 310018China Zhejiang-Mauritius Joint research centerfor biomaterials and Tissue engineering Zhejiang Sci-Tech UniversityHangzhou 310018China School of Textile Science and engineering Zhejiang Sci-Tech UniversityHangzhou 310018China

Herein,the rational design micromilieus involved silk fibroin(SF)-based materials have been used to encapsulate the osteoblasts,forming an extracellular coated shell on the cells,which exhibited the high potential to shift the regulation of osteoblasts to osteocytes by encapsulation *** coating treated cells showed a change in cell morphology from osteoblasts-like to osteocytes-like shape comparedwith untreated ***,the expression of alkaline phosphatase(ALP),collagen I(Col I)and osteocalcin(OcN)further indicated a potential approach for inducingosteoblasts regulation,which typically accelerates calcium deposition and cell calcification,presenting a key role for the SF encapsulation in controlling osteoblasts *** discovery showed that SF-based cell encapsulation could be used for osteoblasts behavior regulation,which offers a great potential to modulate mammalian cells'phenotype involvingalternatingsurrounding cues.

关键词： Cell encapsulation silk fibroin osteoblasts modulation cell differentiation cell calcification

Gold nanorods/tetrahedral DNA composites for chemo-photothermal therapy

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Regenerative biomaterials 2022年第1期9卷 404-413页

作者： Ziyun He Qiusheng Wang Nan Zhang Jianqin Yan Li Li Jun Cao Bin He national engineering research Center for biomaterials College of Biomedical EngineeringSichuan UniversityChengdu 610064China Department of Pharmaceutics School of PharmacyQingdao UniversityQingdao 266073China

Combination therapy is extensively developed for cancer treatment in recent years due to its high ***,we constructed a nanocomposite based on gold nanorods(GNRs)and drug-loaded tetrahedral DNA nanostructures(TDN)for chemophotothermal combinational ***-tumor drug doxorubicin(DOX)was loaded via the insertion within GC base pairs of *** aptamer AS1411 was attached to the apex of TDN(ATDN)to target tumor *** DOX-loaded DNA tetrahedron(ATDN-DOX)was compressed by the GNRs coated with PEI(GNRs@ATDN-DOX)to realize the photothermal function and lysosome *** under the illumination of 808nm infrared laser showed high photothermal conversion and stability due to the protection of PEI *** drug-loading capacity of ATDN-DOX was as high as 314 DOX molecules in per *** positive charge of PEI in GNRs@ATDN-DOX nanocomposites was utilized to achieve excellent cell penetration and induce proton sponge effect for lysosomal *** nanocomposites presented HeLa and 4T1 cells targeting and resulted in efficient anticancer activity.

关键词： nanocomposite DNA tetrahedron gold nanorod chemo-photothermal therapy

Polypeptide dendrimers: Self-assembly and drug delivery

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Science China Chemistry 2011年第2期54卷 326-333页

作者： XU XiangHui LI CaiXia LI HaiPing LIU Rong JIANG Chao WU Yao HE Bin GU ZhongWei national engineering research Center for biomaterials Sichuan University Chengdu 610064 China

Amphiphilic dendritic poly（glutarnic acid）-b-polyphenylalanine copolymers were synthesized using generation 3 dendritic poly（glutamic acid） as the macroinitiator in the ring-opening polymerization of NCA-Phe. The block copolymers self-assembled micelles with polyphenylalanine segments as core and dendritic poly（glutamic acid） segments as shell. The biocompatibility of the micelles was studied. The release of the anticancer drug doxorubicin from the micelles was investigated in vitro. The results showed that the sustaining release of the drug could last for 60 h. The micellar drug release system was efficient in inhibiting the proliferation of HepG2 liver cancer cells, 75% cancer cells were killed under appropriate in vitro incubation.

关键词： serf-assembly dendritic polypeptide block copolymer drug delivery

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The morphology of hydroxyapatite nanoparticles regulates clathrinmediated endocytosis in melanoma cells and resultant anti-tumor efficiency

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Nano research 2022年第7期15卷 6256-6265页

作者： Hongfeng Wu Yuchen Hua Jinjie Wu Qin Zeng Xiao Yang Xiangdong Zhu Xingdong Zhang national engineering research Center for biomaterials Sichuan UniversityChengdu 610064China NMPA Key Laboratory for Quality research and Control of Tissue Regenerative biomaterials&Institute of Regulatory Science for Medical Devices&NMPA research Base of Regulatory Science for Medical Devices Sichuan UniversityChengdu 610064China research Center for Materials Genome engineering Sichuan UniversityChengdu 610064China

Clathrin-mediated endocytosis plays a critical role for hydroxyapatite nanoparticles(HANPs)to enter tumor cells,induce mitochondrial apoptosis,and inhibit tumor *** study was aimed to investigate how the morphology of HANPs impacts the endocytosis of the particles in melanoma cells,and their anti-tumor effect by using in vitro cell experiments and in vivo tumor animal *** shapes of HANPs,including granular HANPs(G-HANPs),rod-like HANPs(R-HANPs),and needle-like HANPs(N-HANPs),were successfully prepared by wet chemical *** the three HANPs could be internalized into A375 melanoma cells as indicated by cellular transmission electron microscopy *** these HANPs,only G-HANPs induced morphological change of mitochondria and loss of mitochondrial membrane potential(Δψm),and exhibited the greatest intracellular internalization efficiency in the tumor ***,the results of immunofluorescence staining and western blotting indicated that the level of adaptin-2(AP2)protein was up-regulated by all the HANPs,and highest in G-HANPs treated A375 ***,in the tumor-bearing mouse model,we found that tumor growth was delayed by all the three HANPs,of which,G-HANPs delayed tumor growth most efficiently and presented a highest expression level of AP2 protein in tumor ***,this study suggested that the morphology of HANPs regulated their endocytosis efficiency and their effect to inhibit tumor *** work facilitates to direct the rational design of nano-materials for tumor therapy.

关键词： hydroxyapatite nanoparticles adaptin-2 protein morphology endocytosis anti-tumor effect

Strategies of strengthening mechanical properties in the osteoinductive calcium phosphate bioceramics

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Regenerative biomaterials 2023年第1期10卷 561-573页

作者： Qipeng Li Cong Feng Quanle Cao Wei Wang Zihan Ma Yonghao Wu Tinghan He Yangtian Jing Wenxuan Tan Tongxiao Liao Jie Xing Xiangfeng Li Ye Wang Yumei Xiao Xiangdong Zhu Xingdong Zhang College of Chemical engineering Sichuan UniversityChengdu 610065China national engineering research Center for biomaterials College of Biomedical EngineeringSichuan UniversityChengdu 610065China College of Materials Science and engineering Sichuan UniversityChengdu 610064China

Calcium phosphate(CaP)bioceramics are widely applied in the bone repairing field attributing to their excellent biological properties,especially ***,their applications in load-bearing or segmental bone defects are severely restricted by the poor mechanical *** is generally considered that it is challenging to improve mechanical and biological properties of CaP bioceramics *** to now,various strategies have been developed to enhance mechanical strengths of CaP ceramics,the achievements in recent researches need to be urgently *** this review,the effective and current means of enhancing mechanical properties of CaP ceramics were comprehensively summarized from the perspectives of fine-grain strengthening,second phase strengthening,and sintering process ***’s more,the further improvement of mechanical properties for CaP ceramics was prospectively proposed including heat treatment and ***,this review put forward the direction about how to compatibly improve mechanical properties of CaP ceramics,which can provide data and ideas for expanding the range of their clinical applications.

关键词： CaP ceramics strategy mechanical property osteoinductivity enhancement

Evaluation on the corrosion resistance, antibacterial property and osteogenic activity of biodegradable Mg-Ca and Mg-Ca-Zn-Ag alloys

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Journal of Magnesium and Alloys 2022年第12期10卷 3380-3396页

作者： Hewei Chen Bo Yuan Rui Zhao Xiao Yang Zhanwen Xiao Antoniac Aurora Bita Ana Iulia Xiangdong Zhu Antoniac Vasile Iulian Xingdong Zhang national engineering research Center for biomaterials Sichuan UniversityChengdu 610064China Faculty of Materials Science and engineering University Politehnica of BucharestBucharest 060042Romania Academy of Romanian Scientists Bucharest 050094Romania

The rapid degradation of magnesium(Mg)-based implants in physiological environment limits its clinical applications, and alloying treatment is an effective way to regulate the degradation rate of Mg-based materials. In the present study, three Mg alloys, including Mg-0.8Ca(denoted as ZQ), Mg-0.8Ca-5Zn-1.5Ag(denoted as ZQ71) and Mg-0.8Ca-5Zn-2.5Ag(denoted as ZQ63), were fabricated by alloying with calcium(Ca), zinc(Zn) and silver(Ag). The results obtained from electrochemical corrosion tests and in vitro degradation evaluation demonstrated that the three Mg alloys exhibited distinct corrosion resistance, and ZQ71 exhibited the lowest degradation rate in vitro among them. After addition of Zn and Ag, the antibacterial potential of Mg alloys was also enhanced. The in vitro cell experiments showed that all the three Mg alloys had good biocompatibility. After implantation in a rat femoral defect, ZQ71 showed significantly higher osteogenic activity and bone substitution rate than ZQ63 and ZQ, due to its higher corrosion resistance as well as the stimulatory effects of the released metallic ions. In addition, the average daily degradation rate of each Mg alloy in vivo was significantly higher than that in vitro, as could be due to the implantation site located in the highly vascularized trabecular region. Importantly, the correlations between the in vitro and in vivo degradation parameters of the Mg alloys were systematically analyzed to find out the potential predictors of the in vivo degradation performance of the materials. The current work not only evaluated the clinical potential of the three biodegradable Mg alloys as bone grafts but also provided a feasible approach for predicting the in vivo degradation behavior of biodegradable materials.

关键词： Mg alloys Degradability Antibacterial property Osteogenic ability Bone defect repair