Wang Sijie, Zhou Huanli, Mao Jiapeng, Zhang Yitao, Qi Yuxin, Pang Mei, Jin Xizhi, Zhang Junlei, Luo Lihua, You Jian
College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, PR China.
College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, PR China.
Biomaterials. 2025 Dec;323:123420. doi: 10.1016/j.biomaterials.2025.123420. Epub 2025 May 20.
Refractory pulmonary diseases, including chronic obstructive pulmonary disease (COPD) and tuberculosis (TB), pose a critical global health challenge due to the limitations of conventional therapies in advanced stages, such as poor drug penetration, systemic side effects, and inability to eradicate pathogens in protected microenvironments. While the lung's complex structure is essential for respiratory function, it also facilitates persistent damage from environmental and infectious agents. Nanomedicine provides a transformative approach by utilizing customizable carriers (e.g., ligand-gated targeting, stimuli-responsive payload release) to bypass physiological barriers through both passive mechanisms such as enhanced vascular permeability and active-targeting. Such platforms achieve hierarchical drug deposition-from organ-level accumulation to pneumonocyte-targeting-thereby addressing the spatial heterogeneity of therapy-resistant lesions. Besides, A unique advantage of nanomedicine lies in its intrinsic interactions with lung immune cells (e.g., macrophages), allowing dual-functional systems that not only deliver therapeutics to disease sites but also modulate local immune responses-such as reducing inflammation in COPD or enhancing bacterial clearance in TB. This targeted approach improves treatment efficacy while minimizing systemic toxicity. Furthermore, nanomedicine ensures the stability of encapsulated drugs, particularly nucleic acid therapeutics (siRNA, mRNA), which are crucial for treating genetic defect-related pulmonary diseases. Building on the relationship between malignant pulmonary conditions and lung cells, this review summarizes nanoplatform-based strategies for precise targeting and examines ongoing clinical trials. By bridging the gap between preclinical research and clinical application, this review aims to guide the development of novel therapeutic approaches and accelerate the clinical translation of nanomedicines for refractory pulmonary diseases.
难治性肺部疾病，包括慢性阻塞性肺疾病（COPD）和肺结核（TB），由于传统疗法在疾病晚期存在局限性，如药物渗透差、全身副作用以及无法在受保护的微环境中根除病原体，对全球健康构成了严峻挑战。虽然肺的复杂结构对呼吸功能至关重要，但它也容易受到环境和感染因子的持续损害。纳米医学提供了一种变革性方法，通过利用可定制的载体（如配体门控靶向、刺激响应性载药释放），借助增强血管通透性等被动机制和主动靶向绕过生理屏障。此类平台实现了分级药物沉积——从器官水平的积累到肺细胞靶向——从而解决了耐药性病变的空间异质性问题。此外，纳米医学的一个独特优势在于其与肺免疫细胞（如巨噬细胞）的内在相互作用，使得双功能系统不仅能将治疗药物递送至疾病部位，还能调节局部免疫反应——如减轻COPD中的炎症或增强TB中的细菌清除。这种靶向方法提高了治疗效果，同时将全身毒性降至最低。此外，纳米医学确保了封装药物的稳定性，特别是核酸治疗药物（siRNA、mRNA），这对于治疗与基因缺陷相关的肺部疾病至关重要。基于恶性肺部疾病与肺细胞之间的关系，本综述总结了基于纳米平台的精确靶向策略，并审视了正在进行的临床试验。通过弥合临床前研究与临床应用之间的差距，本综述旨在指导新型治疗方法的开发，并加速纳米药物用于难治性肺部疾病的临床转化。
