CARBOHYDRATE POLYMERS
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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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DOI
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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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PubMed
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ACS Omega
·
2024
·
IF 3.7
Hui-Qin Liu,Xi-Dong Wu,Xue-Wen Fang,Yun-Song An,Meng Xia,Xiao-Hua Luo,Jun-Zheng Li,Guan-Hai Wang,Tao Liu
Nasopharyngeal carcinoma (NPC) is prevalent in Southern China. Unfortunately, current treatments encounter multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), resulting in the efflux of chemotherapy drugs, is one of the significant mechanisms causing MDR. d-α-Tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) has been demonstrated to effectively inhibit P-gp expression. The objectives of this study are to improve tumor MRI imaging, optimize docetaxel (DOC) administration, and target P-gp to overcome NPC resistance. Multifunctional micelles of TPGS (MM@DOC), loaded with magnetic nanoparticles, were synthesized for the targeted delivery of the first-line anticancer drug. MM@DOC exhibited greater toxicity and induced higher levels of apoptosis in DOC-resistant NPC cells (C666–1/DOC) compared to DOC. MM@DOC loaded with magnetic nanoparticles improved the quality of tumor MRI imaging. MM@DOC also demonstrated significant antitumor effects in nude mice with C666–1/DOC NPC. In conclusion, MM@DOC exhibited promising inhibitory effects on resistant tumors both in vitro and in vivo, optimized tumor MRI imaging, and showed great potential in drug delivery and overcoming resistance.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
·
IF 9.4
Xinyu Lu,Yuxuan He,Jipeng Xiao,Jiali Lian,Qiao Guo,Yuchen Jiang,Ying Chen,Yongchao Yao,Liyun Bi,Hualin Cheng,Jianbin Luo
Photodynamic therapy (PDT) employs reactive oxygen species (ROS) from a photosensitizer (PS) under light, inhibiting multi-drug resistance in bacteria. However, hypoxic conditions in infection sites and biofilms challenge PDT efficiency. We developed fluorinated small molecular micelles (PF-CBMs) as PS carriers to address this, relieving hypoxia and enhancing PS penetration into biofilms. Perfluorocarbons in PF-CBMs transport more oxygen due to their excellent oxygen-dissolving capability. Fluorination enhances loading capacity and serum stability, reduces premature release, and improves cellular uptake, to improve PDT efficacy. PF-CBMs, with acid-induced surface charge transformation, exhibit superior biofilm penetration, resulting in increased antibiofilm activity of PDT. Compared to fluorine-free micelles (PC-CBMs), PF-CBMs demonstrate better serum stability, higher drug loading, and reduced premature release, leading to significantly improved antibacterial efficacy in vitro and in vivo . In conclusion, fluorinated micelles with surface charge reversal enhance PDT for antibacterial and antibiofilm applications.
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ACS Applied Nano Materials
·
2024
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IF 5.3
Sifang Zhao,Fengjiao Chen,Xianwu Chen,Hongze Liang,Hui Tan,Lingling Zhao
The tumor microenvironment is characterized by several hallmarks such as an acidic pH and high glucose levels in tumor tissues and increased expression of specific proteins and/or sugars on the surface of tumor cells. These unique hallmarks of tumors can be considered in the design of multifunctional drug delivery nanosystems to improve the efficiency of tumor therapy through targeted drug delivery and specific drug release in the tumor tissue. In this study, phenylboronic acid-modified pH- and glucose-responsive polymer micelles were designed for the targeted delivery of anticancer drugs. The polymeric micelles demonstrated prolonged and pH/glucose-triggered drug release and enhanced cellular internalization by B16F10 cells through a receptor-mediated endocytosis pathway. The polymeric micellar system could inhibit the proliferation of B16F10 cells with IC50 values lower than those of unmodified micelles. In addition, the polymeric micellar system could markedly suppress cell migration, colony formation, and invasion and promote the apoptosis of B16F10 cells, indicating good anticancer efficiency in vitro. Therefore, this polymeric nanocarrier provides a potential platform for targeted anticancer therapy.
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SENSORS AND ACTUATORS B-CHEMICAL
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2024
·
IF 8
Siyi Li,Kexin Li,Xianfeng Gong,Pengfei Yan,Shaoping Sun
Multifunctional polymeric micelles, which possess capabilities for tracking, bioimaging, stimuli-responsive drug release and tumor targeting, are essential in facilitating the effective delivery of anticancer drugs. Hence, a novel copolymer (CD-CS-Bio-TPAA, CCBT) was synthesized with biotin and hydroxypropyl-β-cyclodextrin conjugated chitosan as the hydrophilic segment and aggregation-induced emission (AIE) featured tetraphenylethene derivative (TPAA) as the hydrophobic segment. Interestingly, under acidic conditions, CCBT exhibited color-tunable AIE behavior as a result of the cleavage of benzoic imine bonds in TPAA molecules, transitioning from red to yellow. Furthermore, CCBT could also self-assemble into polymeric micelles and be used as drug carriers to encapsulate paclitaxel (PTX) (PTX/CCBT PMs) for self-indicating cancer therapy. In vitro release experiments demonstrated that PTX/CCBT PMs could release drugs specifically under acidic conditions. Fluorescence imaging experiments demonstrated that CCBT PMs exhibited excellent cell imaging capabilities and could be tracked due to their unique color-changing behavior. Moreover, PTX/CCBT PMs exhibited notable cytotoxic effects on MCF-7 cells and showed selective internalization by MCF-7 cells through biotin receptor-mediated active targeting. In vivo antitumor experiments confirmed that PTX/CCBT PMs possessed remarkable tumor-inhibiting effects and low systemic toxicity. This work suggested that PTX/CCBT PMs provided new ideas for self-indicating breast cancer treatment.
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MACROMOLECULES
·
2024
·
IF 5.1
Yanran Li,Jun Ma,Yanbin Fan,Chen Zheng,Daoyong Chen
Structures impact the performance of nanocatalysts, but optimizing them by altering their structures is tedious and restricted. We present a strategy using “high energy” polymeric composite micelles as precursors to produce variously structured nanocatalysts in a simple, temporally controlled manner. By incubating core–shell spherical micelles of poly(ethylene glycol)-b-poly(4-vinylpyridine) with a molybdate hydrate complexable with poly(4-vinylpyridine), the molybdates cross-link and enlarge the confined poly(4-vinylpyridine) core, producing “high-energy” and “crosslinking-locked” polymeric composite micelles. Properly increasing the temperature weakens the cross-linking and releases the energy at a suitable rate, facilitating the stepwise transition of the polymeric composite micelles into various structures. Cooling the system at specific phases generates worm-like, flower-like, and clustered structures that further develop into molybdenum phosphide (MoP) nanoworms, nanoflowers, and nanoclusters, respectively. MoP nanoworms demonstrate the highest efficiency as nanoelectrocatalysts for hydrogen evolution, surpassing previously reported MoP-based catalysts and even commercial Pt/C catalysts in high current density regions.
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Colloid and Interface Science Communications
·
2025
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IF 4.7
Zhanglong Huang,Shiwei Ding,Lili Zhong,Chenxi Liu,Xiaofei Li,Dan He
Combination therapy holds great promise for enhancing antitumor efficacy by achieving tumor-targeted and sequentially synergistic cytotoxicity. We developed a tumor-targeted hybrid micellar nanoplatform that co-delivers the chemotherapeutic agent pemetrexed (PEM) and carbon monoxide (CO) for synergistic chemo-gas therapy. PEM and Fe₃(CO)₁₂ were covalently conjugated to D-α-tocopheryl polyethylene glycol succinate (TPGS), yielding two amphiphilic prodrugs—TPGS-PEM and TPGS-CO—which were co-assembled into hybrid micelles. The presence of PEM enabled folate receptor-mediated active targeting, resulting in efficient uptake by 4T1 breast cancer cells. Intracellular esterase-catalyzed cleavage of the ester bond released PEM, which elevated reactive oxygen species (ROS) levels. The increase in ROS triggered site-specific CO release from the Fe–CO complex. This sequential mechanism enabled a cascade of tumor-selective chemotherapy and gas therapy, leading to enhanced apoptosis and reduced tumor proliferation. The hybrid micelles exhibited superior tumor suppression, reduced systemic toxicity, and prolonged survival in tumor-bearing mice.
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Journal of Materials Chemistry B
·
2025
·
IF 5.7
Yu Li,Pei Xie,Ruixin Gong,Junlong Chen,Yaxue Liu,Zongning Yin
Rheumatoid arthritis (RA), a chronic autoimmune disorder affecting 1% globally, urgently demands advanced therapies to overcome the systemic toxicity and limited efficacy of conventional glucocorticoids like dexamethasone (Dex). In this study, we constructed LMWH-Gly-Pro-ODA/Dex (LGPO/Dex) micelles, which synergistically integrate low molecular weight heparin (LMWH)-mediated active targeting with Gly-Pro-mediated fibroblast-activated protein (FAP)-α-responsive drug release to achieve spatiotemporal precision in RA treatment. The system operates through a three-stage cascade mechanism: (1) targeting the inflamed joints, (2) inflammation-responsive drug release to modulate pathological microenvironments (e.g., normalizing M1/M2 macrophage polarization), and (3) suppression of monocyte recruitment to prevent disease progression. LGPO/Dex micelles showed excellent RA therapeutic effects in the adjuvant-induced arthritis (AIA) model. Joint swelling, serum TNF-α, and nitric oxide (NO) levels in LGPO/Dex-treated rats showed no significant difference from healthy controls (ns) while exhibiting marked improvement over Dex monotherapy (**, P < 0.01). Notably, it also significantly reduced Dex-associated adverse effects. This study confirmed the feasibility of using FAP-α as a therapeutic target for RA and provided a new idea for RA treatment, offering a blueprint for disease-microenvironment-programmed therapeutics.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Yanmei Shi,Ronghua Tan,Chan Yu,Ying Wan
Image-guided chemo-photothermal therapy based on near-infrared (NIR) theranostic agents has found promising applications in treating tumors. In this multimodal treatment, it is of critical importance to image real-time distribution of photothermal agents in vivo and to monitor therapeutic outcomes for implementing personalized treatment. In this study, an optimally synthesized dextran-polylactide (DEX-PLA) copolymer was assembled with doxorubicin (DOX) and DiR, a kind of NIR dye, to construct desirable micelles ((DiR + DOX)/DEX-PLA) for performing image-guided chemo-photothermal therapy. These (DiR + DOX)/DEX-PLA micelles had good physical and photothermal stability in aqueous media and showed high photothermal efficiency in vivo. Based on the H22-tumor-bearing mouse model, (DiR + DOX)/DEX-PLA micelles were found to accumulate inside tumors sustainably and to emit strong fluorescence signals for more than three days. The (DiR + DOX)@DEX-PLA micelles together with NIR laser irradiation were able to highly inhibit tumor growth or even eradicate tumors with one injection and two dose-designated 5-minute laser irradiations at the tumor site during 14 days of treatment. Furthermore, they showed almost no impairment to the body of the treated mice. These (DiR + DOX)@DEX-PLA micelles have confirmative translational potential in clinical tumor therapy on account of their persistent image-guided capacity, high antitumor efficacy and good in vivo safety.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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Journal of Materials Chemistry C
·
2013
·Vol. 1
·期 36
·5756-5764
·
IF 0
Lingzhi Zhang,Chengcheng Zhao,Jinping Zhou,Tetsuo Kondo
Amphiphilic cationic cellulose derivatives with different long alkyl chains as hydrophobic segments were synthesized. They can self-assemble into cationic micelles in distilled water. The structure and properties of the micelles were characterized by elemental analysis, FT-IR, 1H NMR, ζ-potential measurements, DLS, TEM, and fluorescence spectroscopy. The hydrophobic cores of the micelles were used to load a hydrophobic dye (4,7-bis[4-(1,2,2-triphenylvinyl)phenyl]benzo-2,1,3-thiadiazole, BTPETD) and exhibited a stable photoluminescence. The fluorescence emission can quantitatively and sensitively respond to 2,4-dinitrophenol (DNP) and picric acid (PA) due to the electron transfer between BTPETD and the explosives, and the limit of detection was 200 and 50 nM for DNP and PA, respectively. The novel hydrophobically modified cationic cellulose micelles have the potential to prepare feasible, sensitive and stable sensor systems for detecting explosives in aqueous solutions.
研究领域:
材料科学
·
分析化学
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DOI
MACROMOLECULAR BIOSCIENCE
·
2018
·Vol. 18
·期 3
·1700339
·
IF 3.392
Xuelin Wang,Juanjuan Li,Qi Yan,Yanrui Chen,Aiping Fan,Zheng Wang,Yanjun Zhao
Redox-responsive micelles are versatile nanoplatforms for on-demand drug delivery, but the in situ evaluation of drug release is challenging. Fluorescence resonance energy transfer (FRET) technique shows potential for addressing this, while the aggregation-caused quenching effect limits the assay sensitivity. The aim of the current work is to combine aggregation-induced emission (AIE) probe with FRET to realize drug release assessment from micelles. Tetraphenylethene (TPE) is selected as AIE dye and curcumin (Cur) is chosen as the model drug as well as FRET receptor. The drug is covalently linked to a block copolymer via the disulfide bond linker and TPE is also chemically linked to the polymer via an amide bond; the obtained amphiphilic polymer conjugate self-assembles into micelles with a hydrodynamic size of ≈125 nm. Upon the supplement of glutathione or tris(2-carboxyethyl)phosphine) trigger (10 × 10 −3 m ), the drug release induces the fluorescence increase of both TPE and Cur. Accompanied with the FRET decay, absorption enhancement and particle size increase are observed. The same phenomenon is observed in MCF-7 cells. The FRET–AIE approach can be a useful addition to the spectrum of available methods for monitoring drug release from stimuli-responsive nanomedicine.
研究领域:
纳米技术
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药学
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生物医学工程
·
化学
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