State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
Department of Interventional and Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
ACS Appl Mater Interfaces. 2021 Jul 14;13(27):31440-31451. doi: 10.1021/acsami.1c06440. Epub 2021 Jun 29.
Activatable nanoscale drug delivery systems (NDDSs) are promising in maximizing cancer specificity and anticancer efficacy, and a multifunctional metal-organic nanomaterial is one of the new star NDDSs which requires further exploration. Herein, a novel DOX@MnCPs/PEG NDDSs were constructed by first synthesizing Mn-sealed coordination particles (MnCPs), modified with a targeted PEGylated polymer, and then loading anticancer drug doxorubicin (DOX). MnCPs were prepared from the assembly of Mn ions and hematoporphyrin monomethyl ether (HMME) molecules. Furthermore, MnCPs had an average size of ∼100 nm and a large surface area (∼52.6 m g) and porosity (∼3.6 nm). After the loading of DOX, DOX@MnCPs/PEG exhibited a high DOX-loading efficacy of 27.2%, and they reacted with glutathione (GSH) to confer structural collapse, leading to the production of Mn ions for enhanced magnetic resonance imaging (MRI), free HMME for augmented photodynamic effect, and free DOX for chemotherapy. As a consequence, these DOX@MnCPs/PEG NDDSs after intravenous injection showed efficient tumor homing and then exerted an obvious suppression for tumor growth rate by synergistic photodynamic-chemo therapy . Importantly, most of the DOX@MnCPs/PEG NDDSs could be gradually cleared through the renal pathway, and the remaining part could slowly be metabolized via the feces, enabling high biosafety. Therefore, this work provides a type of GSH-sensitive NDDS with biosafety, caner specificity, and multifunctionality for high synergistic treatment efficacy.
可激活的纳米药物递送系统（NDDS）在最大限度地提高癌症特异性和抗癌疗效方面具有广阔的前景，多功能金属有机纳米材料是新型 NDDS 之一，需要进一步探索。在此，通过首先合成 Mn 密封配位颗粒（MnCPs）、用靶向 PEG 化聚合物进行修饰，然后负载抗癌药物阿霉素（DOX），构建了一种新型的 DOX@MnCPs/PEG NDDS。MnCPs 是由 Mn 离子和血卟啉单甲醚（HMME）分子组装而成的。此外，MnCPs 的平均粒径约为 100nm，具有较大的表面积（约 52.6m g）和孔隙率（约 3.6nm）。负载 DOX 后，DOX@MnCPs/PEG 表现出高达 27.2%的 DOX 负载效率，并且与谷胱甘肽（GSH）反应导致结构塌陷，产生 Mn 离子以增强磁共振成像（MRI），游离的 HMME 以增强光动力效应，以及游离的 DOX 进行化疗。结果，这些 DOX@MnCPs/PEG NDDS 经静脉注射后表现出高效的肿瘤归巢作用，然后通过协同光动力-化疗对肿瘤生长速度产生明显抑制作用。重要的是，大部分 DOX@MnCPs/PEG NDDS 可通过肾脏途径逐渐清除，剩余部分可通过粪便缓慢代谢，具有较高的生物安全性。因此，这项工作为具有生物安全性、肿瘤特异性和多功能性的 GSH 敏感 NDDS 提供了一种新的治疗方法，以实现高效的协同治疗效果。
