Department of Pharmaceutics, Shenyang Pharmaceutical University, No.103, Wenhua Road, Shenyang, China.
Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, No.103, Wenhua Road, Shenyang 110016, China.
Colloids Surf B Biointerfaces. 2022 Jan;209(Pt 2):112164. doi: 10.1016/j.colsurfb.2021.112164. Epub 2021 Oct 17.
IR825 is a kind of near-infrared (NIR) small molecule cyanine dye and has distinct near-infrared absorbance and excellent thermal conversion performance. Due to poor stability and insufficient therapy efficacy, various nano-systems have been developed as delivery vehicles for NIR dyes to improve their application in tumor treatment. Herein, we developed an intelligent polymer drug vehicle (Mal-PAH-PEG-DMMA/ poly (ethylene imine) - poly(ε-caprolactone) block polymers, MPPD/PEI-PCL) based on pH-responsive charge-reversal to deliver docetaxel (DTX) and photosensitizer (IR825) for chemo-photothermal combination therapy (MPPD@IR825/DTX NPs). MPPD@IR825/DTX NPs could undergo charge conversion in a slightly acidic microenvironment (pH 6.8), resulted in strong electrostatic repulsion to withdraw the shell of the polymer nanoparticles (MPPD), enhanced cellular uptake and increased drug release. MPPD@IR825/DTX NPs demonstrated nanoscale in size with good mono-dispersity and stability, triggered DTX release in response to acid environment and NIR stimulation, in the same time providing excellent photothermal conversion efficiency. In vitro and In vivo experiments confirmed that charge-reversal polymeric nanoparticles improved antitumor efficiency in 4T1 tumor cell modal than non-charge-reversal polymeric nanoparticles. Furthermore, in comparison with chemotherapy or photothermal therapy in a single treatment mode, chemo-photothermal combination therapy of MPPD@IR825/DTX NPs with laser irradiation showed highly efficient tumor ablation. In addition, the polymeric nanoparticles exhibited good biocompatibility and safety. Therefore, the design of charge-reversal polymeric nanoparticles (MPPD@IR825/DTX NPs) provides a new strategy and promising application for targeting and synergistic chemo-photothermal combination therapy.
IR825 是一种近红外（NIR）小分子菁染料，具有明显的近红外吸收和优异的热转换性能。由于稳定性差和治疗效果不足，各种纳米系统已被开发为 NIR 染料的递送载体，以提高其在肿瘤治疗中的应用。在此，我们开发了一种基于 pH 响应电荷反转的智能聚合物药物载体（Mal-PAH-PEG-DMMA/聚（乙二胺）-聚（ε-己内酯）嵌段聚合物，MPPD/PEI-PCL），用于递送多西他赛（DTX）和光敏剂（IR825）进行化疗-光热联合治疗（MPPD@IR825/DTX NPs）。MPPD@IR825/DTX NPs 在微酸性环境（pH 6.8）下可以发生电荷转换，导致强烈的静电排斥作用，使聚合物纳米粒子的壳层缩回，增强细胞摄取并增加药物释放。MPPD@IR825/DTX NPs 呈纳米级大小，具有良好的单分散性和稳定性，在酸性环境和 NIR 刺激下触发 DTX 释放，同时提供出色的光热转换效率。体外和体内实验证实，电荷反转聚合物纳米粒子比非电荷反转聚合物纳米粒子在 4T1 肿瘤细胞模型中提高了抗肿瘤效率。此外，与单一治疗模式的化疗或光热治疗相比，激光照射下的 MPPD@IR825/DTX NPs 化学-光热联合治疗具有高效的肿瘤消融作用。此外，聚合物纳米粒子表现出良好的生物相容性和安全性。因此，电荷反转聚合物纳米粒子（MPPD@IR825/DTX NPs）的设计为靶向协同化学-光热联合治疗提供了一种新的策略和有前途的应用。
