Pediatric Research Institute, Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, 518038, Guangdong, People's Republic of China.
School of Materials and Energy and Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices, Southwest University, Chongqing, 400715, People's Republic of China.
J Nanobiotechnology. 2021 Dec 28;19(1):455. doi: 10.1186/s12951-021-01217-4.
The complex tumor microenvironment and non-targeting drugs limit the efficacy of clinical tumor therapy. For ensuring the accurate delivery and maximal effects of anticancer drugs, it is important to develop innovative drug delivery system based on nano-strategies.
In this study, an intracellular acidity-responsive polymeric metal organic framework nanoparticle (denoted as DIMP) has been constructed, which can co-deliver the chemotherapy agent of doxorubicin (DOX) and phototherapy agent of indocyanine green (ICG) for breast carcinoma theranostics. Specifically, DIMP possesses a suitable and stable nanometer size and can respond to the acidic microenvironment in cells, thus precisely delivering drugs into target tumor sites and igniting the biological reactions towards cell apoptosis. Following in vivo and in vitro results showed that DIMP could be effectively accumulated in tumor sites and induced powerful immunogenic cell death (ICD) effect.
The designed DIMP displayed its effectiveness in combined photo-chemotherapy with auxiliary of ICD effect under a multimodal imaging monitor. Thus, the present MOF-based strategy may offer a potential paradigm for designing drug-delivery system for image-guided synergistic tumor therapy.
复杂的肿瘤微环境和非靶向药物限制了临床肿瘤治疗的效果。为了确保抗癌药物的准确传递和最大效果，基于纳米策略开发创新药物输送系统非常重要。
在这项研究中，构建了一种细胞内酸度响应性聚合物金属有机骨架纳米粒子（表示为 DIMP），可共同递送化疗药物阿霉素（DOX）和光疗药物吲哚菁绿（ICG）用于乳腺癌治疗。具体而言，DIMP 具有合适且稳定的纳米尺寸，并能响应细胞内的酸性微环境，从而将药物精确递送至靶肿瘤部位并引发细胞凋亡的生物反应。体内和体外结果表明，DIMP 可以有效地在肿瘤部位积累，并诱导强大的免疫原性细胞死亡（ICD）效应。
设计的 DIMP 在多模态成像监测下，通过 ICD 效应辅助，显示出联合光化疗的有效性。因此，基于 MOF 的策略可为图像引导协同肿瘤治疗的药物输送系统设计提供潜在范例。
