Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.
Biomater Sci. 2020 Dec 7;8(23):6754-6763. doi: 10.1039/d0bm01502d. Epub 2020 Nov 3.
Chemophotothermal combination therapy has emerged as a novel and promising strategy to treat cancer. To improve anticancer effectiveness and reduce systemic toxicity, it is essential to trigger drug release at tumor sites or within tumor cells for maximal drug exposure. Herein, we constructed gas-generating mesoporous silica nanoparticles (MSNs) that can load ammonium bicarbonate (ABC) and doxorubicin (DOX) within the pores, encapsulate indocyanine green (ICG) onto the polydopamine (PDA) layer, and modify the RGD peptide on the outer surface [denoted as M(abc)-DOX@PDA-ICG-PEG-RGD] for triggered drug release and targeted chemophotothermal combination therapy. Upon hyperthermia or low pH value, the encapsulated ABC can efficiently generate CO gas, thus enhancing the damage to the PDA layer and accelerating DOX release. In vitro experiments showed that the M(abc)-DOX@PDA-ICG-PEG-RGD significantly enhanced cellular uptake and cytotoxicity, and laser irradiation further increased the endocytic and cytotoxic effects. An in vivo study indicated that the nanoparticles can effectively accumulate at the tumor site and significantly inhibited tumor growth with no side-effects to the normal organs. Thus, this gas-generating MSN-based nanocarrier that can trigger drug release in response to laser irradiation or low pH value holds great potential in enhancing cancer chemophotothermal combination therapy.
化学-光热联合治疗已成为治疗癌症的一种新颖且有前途的策略。为了提高抗癌效果并降低全身毒性，有必要在肿瘤部位或肿瘤细胞内触发药物释放，以实现最大的药物暴露。在此，我们构建了一种产气介孔硅纳米粒子（MSNs），它可以在孔内负载碳酸氢铵（ABC）和阿霉素（DOX），将吲哚菁绿（ICG）包封在聚多巴胺（PDA）层上，并在表面修饰 RGD 肽[表示为 M(abc)-DOX@PDA-ICG-PEG-RGD]，用于触发药物释放和靶向化学-光热联合治疗。在高温或低 pH 值下，包裹的 ABC 可以有效地产生 CO 气体，从而增强对 PDA 层的破坏并加速 DOX 释放。体外实验表明，M(abc)-DOX@PDA-ICG-PEG-RGD 显著增强了细胞摄取和细胞毒性，激光照射进一步增加了内吞作用和细胞毒性。体内研究表明，纳米颗粒可以有效地在肿瘤部位聚集，并显著抑制肿瘤生长，对正常器官没有副作用。因此，这种可以响应激光照射或低 pH 值触发药物释放的产气 MSN 基纳米载体在增强癌症化学-光热联合治疗方面具有巨大潜力。
