Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
MOE Key Laboratory of Glucolipid Metabolic Diseases, Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, College of Chinese Medicine Research, Guangdong Pharmaceutical University, Guangzhou 510006, China.
ACS Appl Mater Interfaces. 2021 Dec 8;13(48):57009-57022. doi: 10.1021/acsami.1c18601. Epub 2021 Nov 22.
Photodynamic therapy (PDT) has attracted extensive attention in the clinical treatment of malignant tumor. However, the acidic and hypoxic conditions of the tumor microenvironment (TME) limit the further application of PDT in the clinic. Herein, we fabricate a new nanoplatform─HPDA@MnO@Ce6/DOX@PEG-RGD (HPMRCD)─by means of coating hollow polydopamine nanoparticles (HPDA) with manganese dioxide (MnO), which is modified by cyclic RGD functionalized poly(ethylene glycol) (PEG) and further co-loaded with a photosensitizer, Chlorin e6 (Ce6), and a chemotherapy drug, doxorubicin (DOX). This nanoplatform could be enriched in tumor tissues, then instantly dissociated under an acidic and HO-rich TME. The dual-responsive release of Mn ions and oxygen (O) can relieve tumor hypoxia, which can be used as a magnetic resonance contrast agent and the latter can enhance the PDT effect. Furthermore, the degradation of HPMRCD leads to an efficient loaded therapeutic molecule release, thus yielding a potential therapy to enhance tumor suppression by adopting the combined chemo-photodynamic therapy.
光动力疗法（PDT）在恶性肿瘤的临床治疗中引起了广泛关注。然而，肿瘤微环境（TME）的酸性和缺氧条件限制了 PDT 在临床上的进一步应用。在此，我们通过在中空聚多巴胺纳米粒子（HPDA）上包覆二氧化锰（MnO），制备了一种新型纳米平台—HPDA@MnO@Ce6/DOX@PEG-RGD（HPMRCD），该纳米平台通过环 RGD 功能化聚乙二醇（PEG）进行了修饰，并进一步共载有光敏剂氯代叶绿素 e6（Ce6）和化疗药物阿霉素（DOX）。该纳米平台可以在肿瘤组织中富集，然后在酸性和富含 HO 的 TME 下迅速解离。Mn 离子和氧气（O）的双重响应释放可以缓解肿瘤缺氧，可用作磁共振对比剂，后者可以增强 PDT 效应。此外，HPMRCD 的降解导致负载的治疗分子的有效释放，从而通过联合化疗-光动力疗法产生增强肿瘤抑制的潜在治疗效果。
