文献：pH-Responsive Dual Drug-Loaded Nanocarriers Based on Poly (2-Ethyl-2-Oxazoline) Modified Black Phosphorus Nanosheets for Cancer Chemo/Photothermal Therapy

作者：Nansha Gao, Chenyang Xing, Haifei Wang, Liwen Feng, Xiaowei Zeng, Lin Mei,Zhengchun Peng

相关产品：H2N-PEOz  氨基 - 聚（2 - 乙基 - 2 - 噁唑啉）

原文摘要：

Synergistic cancer therapy, such as those combining chemotherapeutic and photothermal methods, has stronger treatment effect than that of individual ones. However, it is challenging to efficiently deliver nanocarriers into tumor cells to elevate intracellular drug concentration. Herein, we developed an effective pH-responsive and dual drug co-delivery platform for combined chemo/photothermal therapy. An anticancer drug doxorubicin (DOX) was first loaded onto the surface of black phosphorus (BP). With poly(2-ethyl-2-oxazoline) (PEOz) ligand conjugated onto the polydopamine (PDA) coated BP nanosheets, targeted long circulation and cellular uptake in vivo was significantly improved. With another anticancer drug bortezomib (BTZ) loaded onto the surface of the nanocapsule, the platform can co-deliver two different drugs. The surface charge of the nanocapsule was reversed from negative to positive at the tumor extracellular pH (∼6.8), ionizing the tertiary amide groups along the PEOz chain, thus facilitating the cell internalization of the nanocarrier. The cytotoxicity therapeutic effect of this nanoplatform was further augmented under near-infrared laser irradiation. As such, our DOX-loaded BP@PDA-PEOz-BTZ platform is very promising to synergistic cancer therapy.

DOX和BTZ的纳米药物BP-DOX@PDA-PEOz-BTZ可用于mammary cancer 。PDA层在到达tumor部位之前增强了系统的稳定性，并在后续的修饰中保持了光热效应。随后，用PEOz取代PEG，以延长体内药物循环，增加细胞摄取。同时，构建了ph靶向控释触发系统，以弥补实体tumorTreatment 中化学药物的不足，并依靠高光热转化效率进一步提高其抗tumor作用。该系统不仅有利于提高载药含量、细胞摄取和ph响应释放率，而且对tumor细胞表现出较高的光热活性。

图为：双药载BP-DOX@PDA-PEOz-BTZ示意图

H2N-PEOz或H2N-PEG在BP-DOX@PDA表面上的结合：

PDA（聚多巴胺）包覆的 NSs（纳米结构）首先被置于 HyPure 分子生物学级水中进行重悬。这一步骤至关重要，因为合适的溶剂环境能够为后续的反应提供稳定的基础。接着，通过加入适当数量的氢氧化钠来仔细调整溶液的 pH 值。这一过程需要准确的操作，以确保 pH 值处于适宜的范围内，从而为后续的反应创造良好的条件。在BP@PDA 悬浮液中加入 H2N-PEOz后，将反应体系置于室温且黑暗的环境中进行剧烈搅拌。黑暗的条件可以避免某些可能的光化学反应干扰，而剧烈搅拌则有助于反应物充分混合，促进反应的进行。之后，对 H2N-PEOz 修饰的 NPs（即 BP-DOX@PDA-PEOz）进行纯化处理，并用去离子水反复洗涤，以去除杂质和未反应的物质。采用类似的方法，用 H2N-PEG 代替 H2N-PEOz。同样经过重悬、调整 pH、加入反应物、搅拌、纯化和洗涤等一系列步骤，最终成功制备出了 BP-DOX@PDA-PEG。这一制备过程需要严格的操作和控制，以确保产物的质量和性能。

图为：BP NSs、BP@PDA NSs、BP@PDA-PEG和BP@PDA-PEOz的FTIR光谱

结论：DOXloledBP@PDA-PEOz-BTZ用于联合Chemotherapy 和PTT。证明了PDA涂层可以增强BP NS的生物稳定性和光热活性，还证明了PEOz偶联可以改善靶向的、体内长循环以及pH-和光响应药物释放，表明PEOz是PEG的优良替代品。鉴于其较高的药物封装效率、强烈的细胞摄取和细胞Poison 性，以及低pH触发的光响应性、快速的药物释放，多功能PDA-和peoz修饰的、基于bp的双药物共递送纳米平台在协同Treatment cancer方面具有巨大的潜力。