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智能可变形纳米载体的设计策略及其抗肿瘤应用研究进展

Recent development of smart deformable nanocarriers for antitumor application

:1311-1329
 
近年来, 药物递送系统在肿瘤靶向治疗领域取得了显著进展, 已有多种递药系统获批临床应用。其中, 纳米药物因其能够减少传统小分子化疗药物的毒副作用、提高药物生物利用度,并通过增强通透性与滞留效应(EPR效应)实现肿瘤的被动靶向, 从而显著提升治疗效果, 受到广泛关注。尤其是具备尺寸可调、肿瘤特异性聚集、刺激响应性崩解及形貌转变等多功能的智能可变形纳米载体, 已成为当前纳米递药载体研究的热点。这类载体能够感应肿瘤微环境中的特定刺激信号(如酸性pH值、过氧化还原状态、酶活性或过表达细胞因子), 实现包括尺寸调控、聚集组装、结构崩解与形态重构等在内的多种动态变形行为, 从而提升药物在肿瘤部位的滞留时间、渗透深度及控释能力, 最终获得更优的抗肿瘤疗效。例如在肿瘤组织中实现纳米载体尺寸缩小可增强药物的组织穿透力; 纳米粒子聚集变大会延长药物在病灶处的滞留时间; 而快速响应性崩解则有助于药物在肿瘤局部实现高效释放。这些智能变形策略为纳米药物递送系统提供了更高的治疗可控性与精准性。基于其多样化的响应特性和结构可塑性, 智能变形纳米载体在推动抗肿瘤药物的个体化治疗及联合疗法应用方面展现出巨大潜力。本文综述了近年来基于智能变形纳米载体增强抗肿瘤效果的研究进展,系统梳理了其设计策略, 并深入探讨了其在肿瘤精准治疗中的应用前景。
In recent years, drug delivery systems have made remarkable progress in the field of tumor-targeted therapy, with several platforms already approved for clinical use.Among them, nanomedicines have attracted considerable attention due to their ability to mitigate the side effects of conventional small-molecule chemotherapeutics, improve bioavailability, and passively accumulate at tumor sites via the enhanced permeability and retention(EPR)effect, thereby enhancing therapeutic efficacy.Of particular interest are stimuli-responsive, shape-transformable nanocarriers, which exhibit unique properties such as tunable size, tumor-specific accumulation, and structural adaptability in response to tumor-associated cues.These intelligent deformable nanocarriers are capable of undergoing various dynamic transformations—including aggregation, disassembly, size modulation, and morphological transitions—triggered by specific stimuli in the tumor microenvironment(TME), such as pH, redox potential,enzymes,or cytokines.Such transformations enhance drug retention at tumor sites, improve intratumoral penetration, and enable spatiotemporally controlled drug release, ultimately resulting in superior antitumor efficacy.For instance, nanosystems that shrink in size at tumor sites can promote deeper tissue penetration, while those that aggregate into larger assemblies can prolong local drug retention.Conversely, carriers that disassemble rapidly under tumor-specific stimuli allow for burst release of the encapsulated payload precisely at the disease site.These adaptive features hold great promise for improving the therapeutic performance of nanomedicines. Furthermore, the multifunctionality of intelligent deformable nanocarriers supports the development of personalized treatment regimens and combination therapies, offering novel strategies for cancer management.This review highlights recent advances in the design and application of shape-transformable nanocarriers for enhanced anticancer drug delivery, summarizing design principles and exploring their emerging potential in precision oncology.
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