School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, China.
Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China.
J Colloid Interface Sci. 2024 Dec;675:1080-1090. doi: 10.1016/j.jcis.2024.07.113. Epub 2024 Jul 14.
Premature drug release in chemotherapy and hypoxic conditions in photodynamic therapy (PDT) are perplexing problems in tumor treatment. Thus, it is of great significance to develop the novel therapeutic system with controllable drug release and effective oxygen generation. Herein, a pH-responsive oxygen self-sufficient smart nanoplatform (named DHCCC), integrating hollow mesoporous silica nanoparticles (HMSNs), chitosan (CS), doxorubicin hydrochloride (DOX), chlorin e6 (Ce6) and catalase (CAT), is fabricated to enhance the tumor therapeutic efficacy efficiently through avoiding premature drug release and mitigating hypoxia of tumor microenvironment (TME). The drug DOX can be efficiently loaded into the HMSNs with large cavity and be controllable released because of the pH responsiveness of CS to the weak acidic TME, thereby elevating the chemotherapy efficacy. Meanwhile, CAT can catalyze the decomposition of endogenous hydrogen peroxide in situ generating oxygen to alleviate the hypoxia and enhance the PDT efficiency considerably. In vitro and in vivo results demonstrate that the combined chemo-photodynamic therapy based on the DHCCC nanoplatform exerts more effective antitumor efficacy than chemotherapy or PDT alone. The current study provides a promising inspiration to construct the pH-responsive oxygen self-sufficient smart nanomedicine with potentials to prevent premature drug leakage and overcome hypoxia for efficient tumor therapy.
在化疗中药物过早释放和光动力疗法（PDT）中的缺氧条件是肿瘤治疗中的难题。因此，开发具有可控药物释放和有效生成氧气的新型治疗系统具有重要意义。在此，构建了一种 pH 响应性氧自足智能纳米平台（命名为 DHCCC），它集成了中空介孔硅纳米粒子（HMSNs）、壳聚糖（CS）、盐酸阿霉素（DOX）、氯乙酮（Ce6）和过氧化氢酶（CAT），通过避免药物过早释放和减轻肿瘤微环境（TME）的缺氧，有效地提高了肿瘤治疗效果。由于 CS 对弱酸性 TME 的 pH 响应性，药物 DOX 可以有效地被负载到具有大空腔的 HMSNs 中，并可以进行可控释放，从而提高了化疗效果。同时，CAT 可以催化内源性过氧化氢原位分解生成氧气，从而显著缓解缺氧并提高 PDT 效率。体外和体内实验结果表明，基于 DHCCC 纳米平台的联合化疗-光动力疗法比单独化疗或 PDT 具有更有效的抗肿瘤疗效。本研究为构建具有预防药物过早泄漏和克服缺氧以实现高效肿瘤治疗潜力的 pH 响应性氧自足智能纳米医学提供了有前景的启示。
