文献：Complete ablation of resistant tumors with photosensitive black phosphorus quantum dots-based lipid nanocapsules

文献链接：https://www.sciencedirect.com/science/article/abs/pii/S138589472033998X

作者：Shengyong Geng, Zhibin Li, Rui Zhang, Wenhua Zhou, Guanghong Luo , Paul K. Chu, and Xue-Feng Yua

相关产品：DSPE-PEG2000-cRGD  磷脂-聚乙二醇-靶向穿膜肽

原文摘要：Treatment of drug-resistant tumors is a great challenge and nanoplatforms combining advanced therapeutic functions have many advantages in offering efficient treatment. However, the reported fabrication of nanoplatforms for multi-modal therapy of tumors is complicated or even uncontrollable since several kinds of therapeutic agents need to be assembled into the nanoparticles. Herein, black phosphorus (BP)-based photosensitive nanocapsules (BP-PNCs) are designed as a highly efficient nanoplatform against resistant tumors by integrating the inherent photothermal and chemotherapeutic effects of BP. BPPNCs are synthesized by encapsulating BP quantum dots (BPQDs) into the core of liposome and DSPE-PEG2000-cRGD is incorporated into the liposomal bilayers to render BP-PNCs with high cellular uptake and effective in vivo tumor targeting capability after intravenous injection. In vitro and in vivo assessments demonstrate that BP-PNCs in conjunction with near-infrared (NIR) light irradiation lead to complete obliteration of resistant A549R tumors. The excellent anti-cancer efficacy stems from the synergistic therapeutic effects arising from the NIR light induced BP photothermal effects, which result in hyperthermia ablation and trigger the liposome phase transition to release internal BPQDs to perform BP chemotherapeutic effects. The expression inhibition of P-gp by hyperthermia further improves the chemotherapeutic efficiency. BP-PNCs with a simple structure and intrinsic multi-functionalities have great potential in treating resistant tumors and our results provide insights into the design of multifunctional nanoplatforms for biomedicine.

DSPE-PEG2000-cRGD 是一种具有特定结构和功能的分子，DSPE-PEG2000-cRGD 组成的脂质体或胶束中，可以实现化合物的靶向递送，提高化合物在tumor部位的浓度，增强效果，同时减少化合物对正常组织的副作用。该文献基于黑磷（BP）的光敏纳米胶囊（BP-PNCs）通过整合BP固有作用，作为一种纳米平台。将BPPNCs通过BP量子点（BPQDs）封装到脂质体核心合成，将DSPE-PEG2000-cRGD并入脂质体双层，使静脉注射后BP-PNCs具有高细胞摄取和有效的体内tumor靶向能力。cRGD-lipid（DSPE-PEG2000-cRGD）进一步被纳入脂质体双分子层，使静脉注射后BP-PNCs具有高细胞摄取和体内tumor靶向性。BP-PNCs的具体制备过程如下：

图为：BP-PNCs的制备示意图

DSPE-PEG2000-cRGD在BP-PNCs制备中的应用：

采用改性膜水化法制备了BP-PNC。简而言之，将含有DPPC、胆固醇和DSPE-PEG2000-cRGD的脂粉溶解在圆底瓶中，在减压旋转蒸发器中干燥，生成薄膜。薄膜在真空下进一步干燥过夜，以确保完全去除溶剂。然后用含有BPQDs的PBS水合脂质膜，并进行探针超声处理。超声处理过程中的温度是通过冰水浴来控制的。孵育后离心，去除未封装的BPQDs。BPQDs通过液体剥离合成，BP-PNCs通过膜水化方法制备。简而言之，用DSPE-PEG2000-cRGD组装的脂质体双层膜通过旋转蒸发干燥生成薄膜。通过用磷酸盐缓冲盐水水合脂质膜，将BPQDs封装到脂质体中，随后将BPQDs-脂质悬浮液进行超声处理，形成BP- PNCs。

图为：BP-PNCs的TEM图像

结论：DSPE-PEG2000-cRGD在BP-PNCs制备中具有应用价值，其分子结构和功能特性为BP-PNCs的制备和性能优化提供了新的思路和方法。DSPE-PEG2000-cRGD作为表面修饰剂，改善BP-PNCs的表面性质。其磷脂部分可以与BP-PNCs的表面结合，而PEG2000和cRGD部分则朝向外部，提供稳定性和靶向性。由于cRGD的靶向性，DSPE-PEG2000-cRGD可以引导BP-PNCs特异性地结合到目标细胞上，实现化合物的靶向输送。通过DSPE-PEG2000-cRGD的修饰，BP-PNCs的生物利用度可能会得到提高，因为PEG2000的修饰有助于减少非特异性吸附和免疫反应，从而延长化合物在体内的循环时间。