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新型多刺激响应功能化 PEG 基共递药纳米载体用于多药耐药肿瘤的可持续治疗。

Novel multi-stimuli responsive functionalized PEG-based co-delivery nanovehicles toward sustainable treatments of multidrug resistant tumor.

机构信息

School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China.

Institute of Medical Engineering, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

出版信息

J Mater Chem B. 2021 Feb 15;9(5):1297-1314. doi: 10.1039/d0tb02192j.


DOI:10.1039/d0tb02192j
PMID:33443252
Abstract

The efficacy of ongoing anticancer treatment is often compromised by some barriers, such as low drug content, nonspecific release of drug delivery system, and multidrug resistance (MDR) effect of tumors. Herein, in the research a novel functionalized PEG-based polymer cystine-(polyethylene glycol)2-b-(poly(2-methacryloyloxyethyl ferrocenecarboxylate)2) (Cys-(PEG45)2-b-(PMAOEFC)2) with multi-stimuli sensitive mechanism was constructed, in which doxorubicin (DOX) was chemical bonded through Schiff base structure to provide acid labile DOX prodrug (DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2. Afterwards, paclitaxel (PTX) and its diselenide bond linked PTX dimer were encapsulated into the prodrug through physical loading, to achieve pH and triple redox responsive (DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2@PTX and (DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2@PTX dimer with ultrahigh drugs content. The obtained nanovehicles could self-assemble into globular micelles with good stability based on fluorescence spectra and TEM observation. Moreover, there was a remarkable "reassembly-disassembly" behavior caused by phase transition of micelles under the mimic cancerous physiological environment. DOX and PTX could be on-demand released in acid and redox stress mode, respectively. Meanwhile, in vivo anticancer studies revealed the significant tumor inhibition of nanoformulas. This work offered facile strategies to fabricate drug nanaovehicles with tunable drug content and types, it has a profound significance in overcoming MDR effect, which provided more options for sustainable cancer treatment according to the desired drug dosage and the stage of tumor growth.

摘要

正在进行的抗癌治疗的疗效常常受到一些障碍的影响,例如药物含量低、药物递送系统的非特异性释放以及肿瘤的多药耐药(MDR)效应。在此,研究构建了一种具有多刺激敏感机制的新型功能化聚乙二醇(PEG)基聚合物胱氨酸-(聚乙二醇)2-b-(聚(2-甲氧基乙氧基乙基二茂铁羧酸酯)2)(Cys-(PEG45)2-b-(PMAOEFC)2),其中阿霉素(DOX)通过席夫碱结构化学结合,提供酸不稳定的 DOX 前药(DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2。随后,通过物理负载将紫杉醇(PTX)及其二硒键连接的 PTX 二聚体封装到前药中,以实现 pH 和三重氧化还原响应(DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2@PTX 和(DOX)2-Cys-(PEG45)2-b-(PMAOEFC)2@PTX 二聚体具有超高的药物含量。根据荧光光谱和 TEM 观察,所得纳米载体可以自组装成具有良好稳定性的球形胶束。此外,在模拟癌生理环境下,胶束相转变会产生明显的“再组装-解组装”行为。DOX 和 PTX 可以分别按需在酸性和氧化还原应激模式下释放。同时,体内抗癌研究表明纳米配方具有显著的肿瘤抑制作用。这项工作为制备具有可调药物含量和类型的药物纳米载体提供了简便的策略,对于克服 MDR 效应具有深远意义,根据所需药物剂量和肿瘤生长阶段为可持续癌症治疗提供了更多选择。

相似文献

[1]
Novel multi-stimuli responsive functionalized PEG-based co-delivery nanovehicles toward sustainable treatments of multidrug resistant tumor.

J Mater Chem B. 2021-2-15

[2]
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[3]
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[4]
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[6]
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[7]
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[9]
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[10]
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