COLLOIDS AND SURFACES B-BIOINTERFACES
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2014
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IF 4.287
Yukun Wu,Quanyong Lai,Shuqi Lai,Jing Wu,Wei Wang,Zhi Yuan
Polymeric micelles formed in aqueous solution by assembly of amphiphilic block copolymers have been extensively investigated due to their great potential as drug carriers. However, the stability of polymeric assembly is still one of the major challenges in delivering drugs to tissues and cells. Here, we report a facile route to fabricate core cross-linked (CCL) micelles using an enzymatic polymerization as the cross-linking method. We present synthesis of poly(ethylene glycol)-block-poly(N-isopropyl acrylamide-co-N-(4-hydroxyphenethyl) acrylamide) diblock copolymer PEG-b-P(NIPAAm-co-NHPAAm) via reversible addition-fragmentation chain transfer (RAFT) polymerization. The diblock copolymer was then self-assembled into non-cross-linked (NCL) micelles upon heating above the lower critical solution temperature (LCST), and subsequently cross-linked using horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2 ) as enzyme and oxidant. The characterization of the diblock copolymer and micelles were studied by NMR, DLS, UV–vis, and fluorescence spectroscopy. The fluorescence study reveals that the cross-linking process endows the micelles with much lower critical micelle concentration (CMC). In addition, the drug release study shows that the CCL micelles have lower release amount of doxorubicin (DOX) than the NCL micelles due to the enhanced stability of the CCL micelles by core cross-linking process.
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Polymer Chemistry
·
2013
·Vol. 4
·期 14
·4017-4023
·
IF 5.231
Tongbing Sun,Yong Jin,Rui Qi,Shaojun Peng,Baozhu Fan
A novel diselenide-containing mono-cleavable amphiphilic di-block polymer, denoted MPEG-IPDI-SeSe-IPDI-PPG, composed of one hydrophilic poly(ethylene glycol) monomethyl ether (MPEG) block and one hydrophobic polypropylene glycol (PPG) block, was synthesized via four coupling reactions in sequence. MPEG-IPDI-SeSe-IPDI-PPG is able to self-assemble into spherical micelles in aqueous solution. Subsequently, it was found that the spherical micelles have a oxidation-responsiveness and undergo a morphology transformation from spherical micelles to large compound micelles (LCMs) in an oxidative environment (0.5%wt H2O2) due to the unique oxidation-responsive cleavage of the diselenide group, resulting in an initially fast release of loaded Rhodamine B (RB), followed by slow, continuously increasing release. It is anticipated that these mono-cleavable polymer micelles containing diselenide may find application in the field of drug delivery systems.
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BIOMACROMOLECULES
·
2013
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IF 5.371
Jie Ren,Yanxin Zhang,Ju Zhang,Hongjun Gao,Gan Liu,Rujiang Ma,Yingli An,Deling Kong,Linqi Shi
Herein, a series of biocompatible, robust, pH/sugar-sensitive, core-cross-linked, polyion complex (PIC) micelles based on phenylboronic acid–catechol interaction were developed for protein intracellular delivery. The rationally designed poly(ethylene glycol)-b-poly(glutamic acid-co-glutamicamidophenylboronic acid) (PEG-b-P(Glu-co-GluPBA)) and poly(ethylene glycol)-b-poly(l-lysine-co-ε-3,4-dihydroxyphenylcarboxyl-l-lysine) (PEG-b-P(Lys-co-LysCA)) copolymers were successfully synthesized and self-assembled under neutral aqueous condition to form uniform micelles. These micelles possessed a distinct core-cross-linked core–shell structure comprised of the PEG outer shell and the PGlu/PLys polyion complex core bearing boronate ester cross-linking bonds. The cross-linked micelles displayed superior physiological stabilities compared with their non-cross-linked counterparts while swelling and disassembling in the presence of excess fructose or at endosomal pH. Notably, either negatively or positively charged proteins can be encapsulated into the micelles efficiently under mild conditions. The in vitro release studies showed that the release of protein cargoes under physiological conditions was minimized, while a burst release occurred in response to excess fructose or endosomal pH. The cytotoxicity of micelles was determined by cck-8 assay in HepG2 cells. The cytochrome C loaded micelles could efficiently delivery proteins into HepG2 cells and exhibited enhanced apoptosis ability. Hence, this type of core-cross-linked PIC micelles has opened a new avenue to intracellular protein delivery.
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Acta Biomaterialia
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2017
·
IF 6.319
Jiao Guan,Zun-Qiang Zhou,Mao-Hua Chen,Hui-Yan Li,Da-Nian Tong,Jun Yang,Jing Yao,Zheng-Yun Zhang
In this study, we developed a folate (FA)-conjugated and pH-responsive active targeting micellar system for anti-cancer drug delivery. In this system, FA was attached to the terminal of the hydrophilic segment of poly(lactic acid)–poly( L -lysine) (PLA–PLL), and PLL was modified by a citric acid group. The FA receptor-mediated active targeting and electrostatic interaction between micelles and cell membrane due to a negative-to-positive charge reversal was combined in one micellar anti-cancer drug delivery system to enhance the tumour targeting and cellular internalisation of micelles. In vitro and in vivo anti-cancer studies demonstrated that the doxorubicin-loaded, FA-conjugated and pH-responsive polymeric micelles possess an enhanced and effective cancer efficiency. Statement of significance Negatively charged nano-carriers prolonged anti-cancer drugs’ blood circulation. However it is difficult to be internalised. Therefore, a negative-to-positive charged micelle surface could improve selectivity for tumour cells and increase uptake chance. In this study, we developed a folate (FA)-conjugated and pH-responsive active targeting micellar system for anti-cancer drug delivery. The FA receptor-mediated active targeting and electrostatic interaction between micelles and cell membrane due to a negative-to-positive charge reversal was combined in one micellar anti-cancer drug delivery system to enhance the tumour targeting and cellular internalisation of micelles. In vitro and in vivo anti-cancer studies demonstrated that the doxorubicin-loaded, FA-conjugated and pH-responsive polymeric micelles possess an enhanced and effective cancer efficiency.
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
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2017
·Vol. 17
·期 5
·2873-2880
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IF 1.483
Huang Saiyan,Liu Jieying,Zhu Hao,Hussain Abid,Liu Qing,Li Jing,Shen Yuanyuan,Cheng Jiejun,Guo Shengrong
A novel folate-polyethylene glycol-succinic acid-doxorubicin conjugate (FA-PEG-SA-DOX) micelle loaded with curcumin (CUR) is designed and prepared to target tumor cells via folate-folate receptor interactions and co-deliver chemotherapeutic agent DOX and chemosensitizer CUR for treatment
of multidrug resistant human breast cancer MCF-7/ADR cells. The CUR/FA-PEG-SA-DOX micelles are characterized with the average size of 90.64±0.15 nm and the zeta potential of −15.3±0.8 mV. The CUR and DOX contents of the micelles are 12.07 and 15.69% (w/w), respectively.
The cytotoxicity, cellular uptake and effiux of the micelles are investigated by using MCF-7/ADR cells. The results demonstrate that the CUR/FA-PEG-SA-DOX micelles have greater toxicity (IC50 = 3.10 µg/ml) compared to the free DOX (IC50 = 31.99 µg/ml),
moreover, the micelles present increased cellular uptake and reduced cellular effiux. The combination index of CUR/FA-PEG-SA-DOX micelles was 0.17, which indicate a strong synergistic antitumor efficacy against MCF-7/ADR cells. These results suggest that Curcumin-loaded FA-PEG-SA-DOX micelles
may be a promising nanomedicine for co-delivery dual-drug treatment for cancer.
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JOURNAL OF APPLIED POLYMER SCIENCE
·
2025
·
IF 2.8
Xiaowei Tan,Ziyi Liu,Cuiling Ouyang,Minxin Deng,Jingyi Xiao,Shufen Xiao,Tuo Huang,Siyu Yu,Hezhang Chen,Hui Chu,Jian Chen
Chitosan (CS)-based drug delivery systems often face challenges in obtaining clinical approval. Enhancing the binding affinity of CS-based carriers to target cells, such as tumor cells, is crucial for their translation from bench to bedside. Strategies like crosslinking (NHS-disulfide-NHS) and utilizing materials like albumin have proven effective in strengthening interactions between CS-based nanoparticles and tumor cells, thereby enhancing cellular uptake (cellular avidity). This study presents a novel approach using crosslinked CS nanoparticles loaded with doxorubicin, featuring reduction-responsive drug release and albumin coating. The albumin-coated crosslinked chitosan (ACCC) was assembled via reaction between amino of CS/albumin and NHS-disulfide-NHS. The resulting ACCC nanoparticle micelles demonstrate enhanced stability of the micelles. The hybrid crosslinked network ensures stability while providing ample space for drug loading and achieves reduction-responsive drug release through disulfide bond crosslinking. Moreover, the proposed system possesses excellent biocompatibility. Compared to uncoated crosslinked chitosan nanoparticle micelles, ACCC nanoparticle micelles exhibit potent cytotoxicity against tumor cells, particularly in reducing environment. Fluorescence imaging and flow cytometry analyses confirm the enhanced cellular affinity conferred by albumin coating. These findings underscore the potential of ACCC nanoparticles in improving tumor cell adhesion and anti-tumor efficacy, thus offering promising prospects for translational medicine in CS-based drug delivery.
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Nature Communications
·
2025
·Vol. 16
·期 1
·1-10
·
IF 15.7
Lu Shuo,Liu Yashuang,Dong Jinfeng,Li Xuefeng
Here are described the dilution-driven gel-sol-gel-sol transitions in aromatic hydrotrope/zwitterionic surfactant bi-component aqueous mixtures. Long and entangled wormlike micelles (WLMs) of concentrated erucyl dimethyl amidopropyl betaine (EAPB) solutions sequentially transform into hexagonal liquid crystal phase (H 1 ), highly concentrated spherical micelles (HCSMs), and finally hexagonal close packed micellar phase (HCP) upon gradual introducing an aromatic hydrotrope, sodium salicylate (NaSal). The HCP then successively converts into HCSMs, WLMs, and spherical micelles (SMs) upon further dilution with water, corresponding to a gel-sol-gel-sol transition. This dilution-induced HCSMs to WLMs transition results in an interesting thickening process, which is caused by a slow kinetic process, from the agglomeration and recombination of SMs to long and rigid WLMs via the intermediately formed rodlike micelles. In this work, the sustained adjustment of the competitive self-sorting and co-assembly between hydrotropes and surfactants by dilution was identified, benefitting the creation and application of WLMs fluids with switchable viscosity.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Mo Liu,Zi-xu Zhang,Jia-hua Wang,Rui-bo Guo,Lu Zhang,Liang Kong,Yang Yu,Juan Zang,Yang Liu,Xue-tao Li
Ovarian cancer, a highly lethal form of gynecological cancer globally, has witnessed notable advancements in its treatment through the integration of nanotechnology and immunotherapy. Here, we designed a novel astragalus polysaccharide vector (PDA), encapsulating podophyllotoxin (PPT), and modifying methotrexate (DSPE-PEG 2000 -MTX) on its surface for targeting ovarian cancer cells with high folate receptor expression. We prepared novel MTX-modified PPT-loaded astragalus polysaccharide micelles (MTX-PPT-micelles) by dialysis method and evaluated their characterization, stability, safety and targeting ability. EDU proliferation, apoptosis, wound healing, and macrophage polarization experiments were performed, and a mouse ectopic tumor model and a lung metastasis model were established to evaluate the antitumor effects of MTX-PPT-micelles. The prepared MTX-PPT-micelles had appropriate particle size, good stability and safety, and were able to achieve slow drug release. In vitro and in vivo experiments showed that MTX-PPT-micelles significantly enhanced tumor uptake and apoptosis, and significantly inhibited tumor proliferation, invasion and metastasis processes. In addition, MTX-PPT-micelles could improve tumor immunosuppression by shifting tumor-associated macrophages from M2 to M1 phenotype. In conclusion, this study successfully constructed a novel nano-delivery system to achieve targeted therapy for ovarian cancer by combating tumor cells with immunomodulatory effects on tumor-associated macrophages.
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ACS Applied Nano Materials
·
2025
·
IF 5.5
Su-Yu Yang,Shu-Tong Li,Tian-Hua Li,De-Jin Ma,Jun-Jie Yu,Yang Liu,Yang Yu,Xue-Tao Li,Juan Zang,Zi-Min Yuan,Liang Kong
Hepatocellular carcinoma (HCC) represents a significant health challenge that requires urgent attention, primarily due to the limited application of chemotherapeutic drugs. This limitation arises from the high infiltration of immune cells within the tumor microenvironment, which diminishes the effectiveness of the therapeutic agents. Consequently, exploring the combination of drug therapy with the M1 polarization mechanism is considered a promising strategy to address this issue. In this study, we designed a hierarchically targeted micelle system responsive to reactive oxygen species (ROS), enabling the synergistic delivery of the hydrophobic drugs sorafenib (Sof) and dehydrodiisoeugenol (Deh) through the integration of a ROS-sensitive bond (thioacetal ketones, TK) and a specific targeting group (glycyrrhetinic acid, GA). The results demonstrated that TK-GA-Sof/Deh-Ms exhibited excellent encapsulation efficiency and stability. The cumulative release rates of Sof and Deh from TK-GA-Sof/Deh-Ms at 48 h were recorded as 49.67 ± 0.02% and 43.90 ± 0.01%, respectively. The online SynergyFinder2.0 software was used to calculate a ZIP synergy score of 6.339 for Sof and Deh, indicating synergy. The combination showed a more significant antitumor effect. The IC50 value of TK-GA-Sof/Deh-Ms was 13.21 ± 1.36 μM. Notably, Deh not only promotes the polarization of M1 macrophages but also effectively inhibits the activation of M2 macrophages. In summary, this study introduces a stepwise-targeting micelle system for liver cancer that possesses dual functions─tumor inhibition and macrophage regulation, thereby paving the way for innovative treatment strategies for hepatocellular carcinoma.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2011
·
IF 2.13
Jun Li,Mingwei Zhao,Liqiang Zheng
The wormlike micelles formed by surface active N -alkyl- N -methylpyrrolidinium bromide ionic liquids (ILs) have been investigated in aqueous solution. The typical rheological parameters and the viscoelastic properties of wormlike micelles were characterized by rheological measurements and cryogenic-transmission electron microscopy (cryo-TEM). The typical rheological parameters were further evaluated by Maxwell model and the viscoelastic properties were discussed based on the living polymer model. Cryo-TEM images confirmed the formation of wormlike micelles in aqueous solution. The effect of the hydrocarbon chain length of the ILs on the wormlike micelles formation was also studied.
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CARBOHYDRATE POLYMERS
·
2011
·
IF 3.463
Hongyan Zhu,Fei Liu,Jing Guo,Jianpeng Xue,Zhiyu Qian,Yueqing Gu
Folate modified chitosan micelles were synthesized for cancer-specific targeting and drug delivery. Receptor-mediated uptake and drug delivery were characterized in vitro and in a small animal model of cancer after loading with hydrophobic fluorescent dyes as drug models. Hydrophilic succinic anhydride and hydrophobic octaldehyde were reacted with chitosan respectively to form amphipathic N-succinyl-N′-octyl chitosan (SO-chitosan). SO-chitosan was covalently modified with folate to form folate-modified N-succinyl-N′-octyl chitosan (folate-SO-chitosan). The folate-SO-chitosan micelles were obtained through self-assembling and maintained a stable core-shell structure with average diameter of about 136 nm up to 15 days. The prepared folate-SO-chitosan micelles displayed a good drug loading content (12.17%), entrapment efficiency (69.32%) and sustained release behavior for the model drug fluorescein. The in vitro cellular uptake and in vivo tumor targeting ability of the folate-SO-chitosan micelles were evaluated by fluorescence microscopy and near infrared imaging, respectively. In vitro and in vivo results demonstrated enhanced targeting behaviors in a folate receptor positive tumor model (Bel-7402), which suggests that the folate-SO-chitosan micelles are promising tumor targeting carriers for hydrophobic diagnostic agents as well as anti-tumor agents.
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LANGMUIR
·
2024
·
IF 3.7
Jieheng Zhang,Jianchang Xu,Jiaying Zhang,Yibin Lin,Jiaxin Li,Duoqu Chen,Wenjing Lin,Chufen Yang,Guobin Yi
It is crucial to use simple methods to prepare stable polymeric micelles with multiple functions for cancer treatment. Herein, via a “bottom-up” strategy, we reported the fabrication of β-CD-(PEOSMA-PCPTMA-PPEGMA)21 (βPECP) unimolecular micelles that could simultaneously treat tumors and bacteria with chemotherapy and photodynamic therapy (PDT). The unimolecular micelles consisted of a 21-arm β-cyclodextrin (β-CD) core as a macromolecular initiator, photosensitizer eosin Y (EOS-Y) monomer EOSMA, anticancer drug camptothecin (CPT) monomer, and a hydrophilic shell PEGMA. Camptothecin monomer (CPTMA) could achieve controlled release of the CPT due to the presence of responsively broken disulfide bonds. PEGMA enhanced the biocompatibility of micelles as a hydrophilic shell. Two βPECP with different lengths were synthesized by modulating reaction conditions and the proportion of monomers, which both were self-assembled to unimolecular micelles in water. βPECP unimolecular micelles with higher EOS-Y/CPT content exhibited more excellent 1O2 production, in vitro drug release efficiency, higher cytotoxicity, and superior antibacterial activity. Also, we carried out simulations of the self-assembly and CPT release process of micelles, which agreed with the experiments. This nanosystem, which combines antimicrobial and antitumor functions, provides new ideas for bacteria-mediated tumor clinical chemoresistance.
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