实体瘤在细胞微环境中提供了一系列生物屏障，用于设计基于先进刺激响应材料的药物递送方法。这些肿瘤间和肿瘤内屏障包括穿孔的内皮、肿瘤细胞拥挤、血管分布、淋巴引流阻断效应、细胞外基质（ECM）蛋白、缺氧和酸中毒。基于单刺激响应药物递送系统（DDS）和双刺激响应药物递送系统（DDS）的实体瘤治疗已经获得了触发机会，该系统不仅改善了肿瘤微环境更深部位的药物靶向，而且还提高了抗肿瘤药物的释放效率。以其最低副作用而闻名的单刺激响应材料和双刺激响应材料可分为17个主要组，这些组涉及与靶向实体瘤的微环境成比例的内部和外部刺激抗癌药物载体。此类药物载体的开发可以克服临床试验研究中的障碍，因为它们具有渗透到肿瘤组织中更难以到达的部位的卓越能力。在最近的设计中，这些 DDS 的关键特性，例如对细胞内和细胞外因子的快速响应、具有最小副作用的有效细胞毒性、有效的渗透性以及药物释放的速率和位置，已作为这些材料设计范例的核心问题进行了讨论。© 2024 年。作者获得 Springer-Verlag GmbH Austria（Springer Nature 旗下公司）的独家许可。

The solid tumors provide a series of biological barriers in cellular microenvironment for designing drug delivery methods based on advanced stimuli-responsive materials. These intertumoral and intratumoral barriers consist of perforated endotheliums, tumor cell crowding, vascularity, lymphatic drainage blocking effect, extracellular matrix (ECM) proteins, hypoxia, and acidosis. Triggering opportunities have been drawn for solid tumor therapies based on single and dual stimuli-responsive drug delivery systems (DDSs) that not only improved drug targeting in deeper sites of the tumor microenvironments, but also facilitated the antitumor drug release efficiency. Single and dual stimuli-responsive materials which are known for their lowest side effects can be categorized in 17 main groups which involve to internal and external stimuli anticancer drug carriers in proportion to microenvironments of targeted solid tumors. Development of such drug carriers can circumvent barriers in clinical trial studies based on their superior capabilities in penetrating into more inaccessible sites of the tumor tissues. In recent designs, key characteristics of these DDSs such as fast response to intracellular and extracellular factors, effective cytotoxicity with minimum side effect, efficient permeability, and rate and location of drug release have been discussed as core concerns of designing paradigms of these materials.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.