Srinivasarao Dadi A, Shah Saurabh, Famta Paras, Vambhurkar Ganesh, Jain Naitik, Pindiprolu Sai Kiran S S, Sharma Anamika, Kumar Rahul, Padhy Hara Prasad, Kumari Meenu, Madan Jitender, Srivastava Saurabh
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad, Balanagar, Hyderabad, 500037, Telangana, India.
Aditya Pharmacy College, Surampalem, 533 437, Andhra Pradesh, India.
Drug Deliv Transl Res. 2025 Feb;15(2):407-435. doi: 10.1007/s13346-024-01673-z. Epub 2024 Jul 22.
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.
设计和开发具有位点特异性的高效药物递送技术是当前有效治疗肺癌的迫切需求。材料科学和纳米技术的出现部分帮助药物递送科学家实现了这一目标。已经开发并利用纳米技术方法探索了各种在病理性肿瘤微环境（TME）中发生降解的刺激响应材料用于药物递送应用。纳米颗粒（NPs）由于其尺寸小和高表面积体积比，在肿瘤部位表现出增强的细胞内化、渗透和滞留。这种刺激响应材料的被动积累有助于在肿瘤内实现时空控制和靶向药物递送。在本综述中，我们讨论了TME特有的各种刺激——物理刺激（间质压力、温度和硬度）、化学刺激（pH值、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）。我们提到了一系列基于生物材料的纳米颗粒递送系统，它们对这些刺激作出响应并在TME处控制药物释放。此外，我们讨论了基于纳米颗粒的联合药物递送策略。最后，我们阐述了关于扩大规模、临床转化和监管批准相关挑战的观点。
