设计和开发具有位点特异性的高效药物输送技术是有效治疗肺癌的迫切需要。材料科学和纳米技术的出现部分帮助药物输送科学家实现了这一目标。使用纳米技术方法开发和探索了在病理肿瘤微环境（TME）中经历降解的各种刺激响应材料，用于药物输送应用。纳米颗粒（NP）由于尺寸小和表面积与体积比高，显示出增强的细胞内化、渗透和在肿瘤部位的保留。刺激响应材料的这种被动积累有助于在肿瘤内实现时空控制和靶向药物输送。在这篇综述中，我们讨论了各种物理刺激（间质压力、温度和硬度）、化学刺激（pH、缺氧、氧化应激和氧化还原状态）和生物刺激（受体表达、外排转运蛋白、免疫细胞及其受体或配体）-这是 TME 的特征。我们提到了一系列基于生物材料的纳米颗粒递送系统，这些系统可以响应这些刺激并控制 TME 中的药物释放。此外，我们讨论了基于纳米颗粒的组合药物输送策略。最后，我们提出了对扩大规模、临床转化和监管审批相关挑战的看法。© 2024。控释协会。

Design and development of efficient drug delivery technologies that impart site-specificity is the need of the hour for the effective treatment of lung cancer. The emergence of materials science and nanotechnology partially helped drug delivery scientists to achieve this objective. Various stimuli-responsive materials that undergo degradation at the pathological tumor microenvironment (TME) have been developed and explored for drug delivery applications using nanotechnological approaches. Nanoparticles (NPs), owing to their small size and high surface area to volume ratio, demonstrated enhanced cellular internalization, permeation, and retention at the tumor site. Such passive accumulation of stimuli-responsive materials helped to achieve spatiotemporally controlled and targeted drug delivery within the tumors. In this review, we discussed various stimuli-physical (interstitial pressure, temperature, and stiffness), chemical (pH, hypoxia, oxidative stress, and redox state), and biological (receptor expression, efflux transporters, immune cells, and their receptors or ligands)-that are characteristic to the TME. We mentioned an array of biomaterials-based nanoparticulate delivery systems that respond to these stimuli and control drug release at the TME. Further, we discussed nanoparticle-based combinatorial drug delivery strategies. Finally, we presented our perspectives on challenges related to scale-up, clinical translation, and regulatory approvals.© 2024. Controlled Release Society.