Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 5
·789-796
·
IF 4.776
Lijuan Sun,Tian Qiu,Jiangxin Liu,Ke Miao,Youliang Zhao,Li-Juan Fan
The combination of fluorescence properties and other functions can significantly enhance the multipurpose applications of functional materials. Herein, fluorescent microspheres with strong fluorescence and bioconjugation sites were prepared via the layer-by-layer (LBL) introduction of poly(p-phenylene vinylene) (PPV) with micelles as a spacer on the substrate spheres. At first, the diblock copolymer poly(acrylic acid)-block-polystyrene (PAA-b-PS) was synthesized and assembled into micelles (PSAm) with the carboxylic groups facing outward. Then, the negatively charged PSAm and positively charged PPV polymer precursor (pre-PPV) were alternately introduced into the substrate polystyrene-divinylbenzene microspheres with sulfonic groups on the surface (SPSDVB) followed by thermal elimination to obtain fluorescent SPSDVB-(PPV/PSAm)n microspheres by converting pre-PPV into PPV. The spheres were found to have stable and bright fluorescence with a very clear core–shell structure. The mechanism for fluorescence enhancement with PSAm as the spacer was studied, and the capability for bioconjugation was also demonstrated. This study provides a promising general strategy for the preparation of fluorescent microspheres combining strong emission with different functional groups to meet various applications.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Yong-E. Gao,Shuang Bai,Xiaoxiao Shi,Meili Hou,Xiaoqian Ma,Tian Zhang,Bo Xiao,Peng Xue,Yuejun Kang,Zhigang Xu
Nanomedicine based polymeric prodrug have showed high impact in the inhibition of tumor growth due to its high therapeutic efficiency and improved biocompatibility. Herein, we synthesized a novel star-like amphiphilic copolymer [β-CD–P(Ir- co -OEGMA), denoted as CPIO] through atom transfer radical polymerization (ATRP) to deliver the hydrophilic anticancer drug irinotecan (Ir). The polymer could form monodisperse unimolecular micelles and had excellent stability in aqueous solution. Moreover, the reduction-responsive feature of the micelles facilitated controlled release of drug, thus achieving targeted therapy and reduced toxicity to healthy cells. The in vitro cytotoxicity assays indicated that CPIO had a notable anticancer effect against HeLa and MCF-7 tumor cells. The confocal laser scanning microscopy and flow cytometry experiments revealed that CPIO micelles could be internalized into tumor cells efficiently. Furthermore, the obtained prodrug micelles produced better efficacy compared to free Ir. Moreover, the CPIO micelles showed excellent biocompatibility in vivo after intravenous injection on a mouse model. This study demonstrated that CPIO carrier could provide a rational design of a stimuli-responsive polymeric prodrug for delivery of irinotecan.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2019
·
IF 6.638
Jingdong Rao,Ling Mei,Ji Liu,Xian Tang,Sheng Yin,Chunyu Xia,Jiaojie Wei,Dandan Wan,Xuhui Wang,Yashi Wang,Man Li,Zhirong Zhang,Qin He
Autophagy plays a key role in the stress response of tumor cells, which contributes to cancer cell survival and resistance to chemotherapy by degrading cytoplasmic proteins to provide energy and clear the hazardous substances. Therefore, combined treatment of chemotherapeutics and autophagy inhibitors is thought to obtain a desirable antitumor effect. Nanoparticles (NPs) show potential in tumor-targeting drug delivery because of the enhanced permeability and retention (EPR) effect. However, NPs with fixed particle size cannot achieve optimal delivery effect. Herein, a strategy based on Cu (I)-catalyzed click chemistry-triggered aggregation of azide/alkyne-modified micelles was developed for the co-delivery of the chemotherapeutic drug doxorubicin (Dox) and the autophagy inhibitor wortmannin (Wtmn). In vitro experiments showed that the size of micelles increased in a time-dependent manner, which enhanced micelle accumulation in both B16F10 and 4 T1 cells. The fluorescence resonance energy transfer (FRET) experiment and biodistribution study further demonstrated that the aggregation of micelles through click cycloaddition significantly improved the accumulation of drug-loading micelles at the tumor region. Furthermore, the decreased amount of autophagosomes observed by transmission electron microscopy (TEM), the declined expression of LC3-II, and the increased level of p62 by western blotting and immunohistochemistry (IHC) confirmed the obvious inhibition of autophagy induced by Dox/Wtmn co-loaded size-adjustable micelles, which had a synergistic effect in cancer suppression. In addition, the co-loaded size-adjustable micelles showed outstanding cytotoxicity and antitumor effect. Therefore, this strategy effectively suppressed melanoma and breast cancer in mice. Statement of Significance The therapeutic effects of chemotherapy can be limited by autophagy; hence, combined use of autophagy inhibitors with chemotherapeutics achieves desirable anticancer efficacy. In the present study, we designed size-adjustable micelles by modifying the click reaction substrate azide group and the alkyne group on the surface of micelles, and subsequently, the autophagy inhibitor wortmannin and the chemotherapeutic drug doxorubicin were co-loaded. The micelles could aggregate by click reaction at the tumor site when the catalysts were intratumorally injected. The results showed that the size-adjustable micelles achieved efficient drug delivery, penetration, and retention in tumors; through the combined effect of wortmannin-mediated autophagy inhibition and doxorubicin-mediated cytotoxicity, this strategy exerted significant anticancer effect in melanoma and breast cancer treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2017
·Vol. 13
·期 12
·1631-1646
·
IF 4.521
Wang Jiao,Liu Qiang,Yang Linnan,Xia Xiaofei,Zhu Rongrong,Chen Shengguang,Wang Mei,Cheng Liming,Wu Xianzheng,Wang Shilong
Cervical cancer is the fourth most common cancer in women worldwide, and existing treatments cause severe side effects and great burdens. Thus, the development of safe, inexpensive therapeutic agents is necessary. Curcumin (Cur), a well-known natural product, exerts promising anti-cancer
activities against various cancer types. However, its therapeutic efficacy is severely restrained due to rapid degradation, poor aqueous solubility, and low bioavailability. The objective of this study was to investigate the therapeutic potential of novel curcumin-loaded TPGS/F127/P123 mixed
polymeric micelles (Cur@NPT100) for cervical cancer treatment. The Cur@NPT100 exhibited an average size of approximately 19 nm, a zeta potential of around –4 mV, a drug loading of 8.18 ± 0.36%, and an encapsulation efficiency of 79.38 ± 4.65%. Unlike free Cur, Cur@NPT100
are readily dispersed in aqueous medium, showing enhanced stability and a sustained release profile over a 6-day period. In vitro cell culture experiments revealed that TPGS/F127/P123 mixed polymeric micelles (NPT100) based nanocarriers substantially promoted the selective cellular
uptake of Cur into HeLa cells rather than by non-cancerous NIH3T3 cells, inducing higher cytotoxicity and greater apoptosis and significantly increasing the percentage of cells arrested at the G2/M phase of the cell cycle. Additionally, the Cur@NPT100 facilitated more Cur accumulation in the
mitochondria and decreased the mitochondrial membrane potential. In addition, western blot assays demonstrated that Cur@NPT100 were more potent than free Cur at activating the mitochondria-mediated apoptosis pathway. In vivo results further confirmed that Cur@NPT100 exhibited a much higher
antitumor efficacy than free Cur and had excellent biocompatibility. In conclusion, Cur@NPT100 might be an effective therapeutic agent for cervical cancer.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2017
·Vol. 5
·期 12
·2501-2510
·
IF 4.21
Zhaopei Guo,Xingzhi Zhou,Mengze Xu,Huayu Tian,Xuesi Chen,Meiwan Chen
Camptothecin (CPT) is a broad spectrum anticancer drug, but its application is limited due to the poor water solubility, lactone ring instability, and low drug loading potential. In this study, biocompatible cationic polypeptide-based micelles were developed to deliver dimeric CPT (DCPT) with the aim of overcoming the above-mentioned obstacles and achieving favorable therapeutic effects. Cationic polypeptide poly-lysine-block-poly-leucine (PLys-b-PLeu) was fabricated via the ring-opening polymerization of N-ε-carbobenzoxy-L-lysine (ε-Lys(Z)) and L-leucine (Leu) and further grafted with polyethylene glycol (PEG) and an arginine-glycine-aspartic acid (RGD) peptide. DCPT was synthesized by reacting CPT and 2-hydroxyethyl disulfide, and micelles were prepared using a dialysis method. The obtained DCPT-loaded RGD-PEG-g-poly-L-lysine-b-poly-L-leucine (DRPPP) micelles showed a high encapsulation efficiency of 89.7% and a high drug loading capacity of 46.1%. In addition, the DRPPP micelles remained stable under physiological conditions (PBS at a pH of 7.4) but showed rapid release when triggered by a reductive environment (PBS at a pH of 7.4 with 10 mM dithiothreitol). Compared to micelles without RGD decoration, the DRPPP micelles exhibited an increased cellular uptake through RGD targeting and were internalized into cells via caveolae-mediated endocytosis and macropinocytosis. Furthermore, the DRPPP micelles exerted an enhanced cytotoxicity against MDA-MB-231 cells compared to MCF-7 cells, which expressed less αvβ3 receptors. Besides, the DRPPP micelles induced cell apoptosis and caused a decrease of mitochondrial membrane potential. These results indicate that dimeric camptothecin-loaded cationic polypeptide-based micelle is a promising strategy for cancer therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 52
·46159-46169
·
IF 3.289
Mingjia Chen,Chunmei Gao,Shaoyu Lü,Yuanmou Chen,Mingzhu Liu
An ideal tumor drug delivery platform should offer little release of the drug in a physiological environment and fast release of the drug once endocytosis into the tumor tissues occurs. Therefore, we have developed a new kind of core-crosslinked copolymers (mPEG-St-SeSex) based on mPEGylated starch and diselenide bonds for rapid drug release. The corresponding core-crosslinked analogs mPEG-St-SSx and mPEG-St-CCx copolymers using 3,3′-dithiodipropionic acid and octanedioic acid as crosslinkers, respectively, were synthesized and used as controls. The results displayed that all amphiphilic core-crosslinked copolymers could form micelles with spherical structures in aqueous solution, showing advanced stability compared to non-crosslinked micelles (mPEG-St) in physiologically related and ultra micelle destabilization conditions. The disassembly of micelles triggered by DTT, combined with in vitro drug release assay and intracellular drug release studies using confocal laser scanning microscopy (CLSM), indicated that the DOX-loaded mPEG-St-SeSex micelles showed higher activity and could be more quickly disrupted than the DOX-loaded mPEG-St-SSx and mPEG-St-CCx micelles in reducing environment and subsequently rapidly released drug. These results, in addition to cell cytotoxicity studies, demonstrated that the mPEG-St-SeSex micelles have the potential to develop controlled drug-delivery systems for cancer therapy.
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2016
·Vol. 12
·期 20
·2731-2740
·
IF 8.315
Zuhong Li,Haibo Wang,Yangjun Chen,Yin Wang,Huan Li,Haijie Han,Tingting Chen,Qiao Jin,Jian Ji
Despite the exciting advances in cancer chemotherapy over past decades, drug resistance in cancer treatment remains one of the primary reasons for therapeutic failure. IR-780 loaded pH-responsive polymeric prodrug micelles with near infrared (NIR) photothermal effect are developed to circumvent the drug resistance in cancer treatment. The polymeric prodrug micelles are stable in physiological environment, while exhibit fast doxorubicin (DOX) release in acidic condition and significant temperature elevation under NIR laser irradiation. Phosphorylcholine-based biomimetic micellar shell and acid-sensitive drug conjugation endow them with prolonged circulation time and reduced premature drug release during circulation to conduct tumor site-specific chemotherapy. The polymeric prodrug micelles combined with NIR laser irradiation could significantly enhance intracellular DOX accumulation and synergistically induce the cell apoptosis in DOX-resistant MCF-7/ADR cells. Meanwhile, the tumor site-specific chemotherapy combined with hyperthermia effect induces significant inhibition of MCF-7/ADR tumor growth in tumor-bearing mice. These results demonstrate that the well-designed IR-780 loaded polymeric prodrug micelles for hyperthermia-assisted site-specific chemotherapy present an effective approach to reverse drug resistance.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2017
·Vol. 19
·期 6
·1-13
·
IF 2.02
Zhang Ran,Wang Shi-Bin,Wu Wen-Guo,Kankala Ranjith Kumar,Chen Ai-Zheng,Liu Yuan-Gang,Fan Jing-Qian
Recently, targeted drug delivery systems (TDDS) have offered a great potential and benefits towards the anti-tumor drug delivery. In this work, we designed the TDDS using a biocompatible poly(ethylene glycol)-poly( β -amino esters) amphiphilic block copolymer (PEG-PAEs) synthesized by Michael addition polymerization for combinatorial therapy. Further, the chemotherapeutic agents’ doxorubicin (DOX) and AS1411 DNA aptamer (Apt) are encapsulated in the PEG-PAEs NPs (PDANs) for co-delivery therapeutics. PDANs have shown the monodisperse spherical shape, smooth surface with a net positive charge (average diameter—183.1 ± 27.2 nm, zeta potential—31.2 ± 6.3 mV), and good colloidal stability (critical micelle concentration of PEG-PAEs is about 6.3 μg/mL). The pH-sensitive PAEs endowed PDANs both pH-triggered drug release characteristics and enhanced endo/lysosomal escape ability, thus improving the localization and cytotoxicity of DOX. AS1411 Apt conjugated PDANs precisely targeted nucleolin and their uptake correlates to a significant activity enhancement only in tumor cells (MCF-7) but not in normal cells (MCF-10A). Thus, PDANs can be a very promising targeted drug delivery platform for effective breast cancer therapy.
Scheme 1 Schematic illustration of the preparation and cellular uptake of targeted co-delivery system
✓ 已验证
产品关联
DOI
高影响因子
Polymer Chemistry
·
2014
·Vol. 5
·期 11
·3707-3718
·
IF 5.368
Yu Han,Junjie Li,Minghui Zan,Shizhong Luo,Zhishen Ge,Shiyong Liu
Responsive cross-linked block copolymer micelles which have emerged as promising drug delivery systems showed high stability and on-demand drug release. The combination therapy of cancer can be achieved via co-delivery of varying therapeutic molecules in one system. Here, we developed a redox-responsive core cross-linked (CCL) micelle conjugated with cypate and cisplatin prodrugs within the cores for synergistic photothermal and chemotherapy. The block copolymer, poly[(2-(2-methoxyethoxy)ethyl methacrylate)-co-(N-methacryloxy succinimide)]-block-poly(N-(2-hydroxypropyl) methacrylamide) (P(MEO2MA-co-MASI)-b-PHPMA), was synthesized via reversible addition–fragment chain transfer (RAFT) polymerization. After partial amidation reaction of succinimide with 3-azidopropylamine, the alkynyl-functionalized cypate and Pt(IV) complex were conjugated via click reaction. The CCL micelles were fabricated by core cross-linking at 37 °C in aqueous solution using cystamine as the cross-linker. P(Pt-Cy-MEO2MA)-b-PHPMA CCL micelles showed redox-responsive cross-linker cleavage and cisplatin drug release in the presence of reductants. The conjugated cypate moieties in the cores of CCL micelles resulted in photothermal temperature increase and reactive oxygen species (ROS) generation under 805 nm near infrared (NIR) laser irradiation. The cytotoxicity of CCL micelles was investigated with and without NIR irradiation. A significant synergistic effect of photothermal therapy and chemotherapy was demonstrated against cisplatin-resistant human lung cancer cells A549R under NIR irradiation.
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 92
·75766-75772
·
IF 3.84
Lei Li,Guohua Jiang,Xiangxiang Du,Hua Chen,Yongkun Liu,Qin Huang,Xiangdong Kong,Juming Yao
A glucose-responsive and fluorescent copolymer was prepared via a one-pot method that combines RAFT polymerization and enzymatic transesterification. The as-prepared copolymer tended to self-assemble into spherical micelles that were confirmed using 1H NMR, FT-IR and GPC, and transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis. Due to the attachment of fluorescent side groups, the optical properties of the micelles were analyzed using a UV-Vis spectrometer, fluorescence spectrophotometer and confocal laser scanning microscopy (CLSM). Owing to the amphiphilic and glucose-responsive properties, the micelles could be used as carriers for loaded insulin. The insulin release behaviour was evaluated when triggered by glucose in vitro. In addition, the resultant micelles exhibited relatively lower cytotoxicity and excellent stability against a protein solution. The insulin retained its structure stability after release, investigated through circular dichroism (CD) spectra analysis. These results showed that the obtained glucose-responsive and fluorescent polymer micelles with a good biological imaging performance and biocompatibility could be one of the effective candidate carriers for controllable release of insulin.
✓ 已验证
产品关联
DOI
高影响因子
Biomed Research International
·
2013
·
IF 0
Li Lv,Yuanyuan Shen,Min Li,Xiaofen Xu,Mingna Li,Shengrong Guo,Shengtang Huang
A novel 4-arm poly(ethylene glycol)-block-poly(anhydride-esters) amphiphilic copolymer (4-arm PEG-b-PAE) was synthesized by esterization of 4-arm poly(ethylene glycol) and poly(anhydride-esters) which was obtained by melt polycondensation of α-, ω-acetic anhydride terminated poly(L-lactic acid). The obtained 4-arm PEG-b-PAE was characterized by 1H-NMR and gel permeation chromatography. The critical micelle concentration of 4-arm PEG-b-PAE was 2.38 μg/mL. The curcumin-loaded 4-arm PEG-b-PAE micelles were prepared by a solid dispersion method and the drug loading content and encapsulation efficiency of the micelles were 7.0% and 85.2%, respectively. The curcumin-loaded micelles were spherical with a hydrodynamic diameter of 151.9 nm. Curcumin was encapsulated within 4-arm PEG-b-PAE micelles amorphously and released from the micelles, faster in pH 5.0 than pH 7.4, presenting one biphasic drug release pattern with rapid release at the initial stage and slow release later. The hemolysis rate of the curcumin-loaded 4-arm PEG-b-PAE micelles was 3.18%, which was below 5%. The IC50 value of the curcumin-loaded micelles against Hela cells was 10.21 μg/mL, lower than the one of free curcumin (25.90 μg/mL). The cellular uptake of the curcumin-loaded micelles in Hela cell increased in a time-dependent manner. The curcumin-loaded micelles could induce G2/M phase cell cycle arrest and apoptosis of Hela cells.
✓ 已验证
产品关联
DOI
PubMed
Materials Science & Engineering C-Materials for Biological Applications
·
2015
·
IF 3.088
Xiaoju Wang,Cuiping Yang,Chenhong Wang,Leijia Guo,Tianhong Zhang,Zhenqing Zhang,Husheng Yan,Keliang Liu
Although PEG remains the gold standard for stealth functionalization in drug delivery field up to date, complete inhibition of protein corona formation on PEG-coated nanoparticles remains a challenge. To improve the stealth property of PEG, herein an α-glutamyl group was conjugated to the end of PEG and polymeric micelles with α-glutamyl-terminated PEG shells were prepared. After incubation with bovine serum albumin or in fetal calf serum, the size of the micelles changed slightly, while the size of the micelles of similar diblock copolymer but without α-glutamyl group increased markedly. These results indicated that the micelles with α-glutamyl-terminated PEG shells showed low non-specific protein adsorption. In vivo blood clearance kinetics assay showed that the micelles with α-glutamyl-terminated PEG shells exhibited a longer in vivo blood circulation time compared with similar micelles but without α-glutamyl groups. The better stealth property of the micelles with α-glutamyl-terminated PEG shells was presumably attributed to the zwitterionic property of the α-glutamyl groups.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）