Li Shimei, Zhang Wei, Lan Xudong, Tan Longfei, Chen Xudong, Lv Kong-Peng, Huang Zhongbing, Gou Li, Wan Jing, Meng Xianwei
Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 29 Zhongguancun East Road, Beijing, 100190, P. R. China.
Department of Interventional Radiology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, P. R. China.
J Biomed Nanotechnol. 2022 Feb 1;18(2):369-380. doi: 10.1166/jbn.2022.3259.
Microwave (MW) hyperthermia has been widely studied in tumor therapy, while the lack of specificity, and the potential toxicity induced by instability or difficulty in degradation of existed MW thermal sensitizers still limits the application. Herein, a new biocompatible Poly(lactic-co-glycolic acid) (PLGA)-based nanosensitizer of Dtxl-Gd@PLGA-PEG-TPP (DGPPT) with capacities of magnetic resonance (MR) imaging and mitochondrial targeting for MW hyperthermia combined with chemotherapy was constructed via a double emulsion solvent evaporation method. The modified TPP significantly enhanced the specificity of sensitizer for targeting mitochondria, a heat-sensitive energy supply plant in cells. Thus the MW thermal damage induced by the loaded Gd in PLGA nanospheres was also strengthened. Together, the system could also achieve MR imaging due to the existence of Gd. In addition, the encapsulated Dtxl performed the chemotherapy of inhibiting mitochondrial function for assisting with MW hyperthermia. experiments demonstrated that PLGA had high biocompatibility that no obvious damage occurred even the dose was up to 200 mg/kg. Meanwhile, DGPPT+MW representing the combination of mitochondrial targeting and MW hyperthermia-chemotherapy has also been proved to shrink tumor size effectively. This study provides a new direction for building biosafe and multifunctional MW sensitizer with active targeting ability to impede tumor growth.
微波（MW）热疗在肿瘤治疗中已得到广泛研究，然而，由于缺乏特异性，以及现有MW热敏剂的不稳定性或降解困难所导致的潜在毒性，仍然限制了其应用。在此，通过双乳液溶剂蒸发法构建了一种新型的基于聚乳酸-羟基乙酸共聚物（PLGA）的生物相容性纳米敏化剂Dtxl-Gd@PLGA-PEG-TPP（DGPPT），其具有磁共振（MR）成像和线粒体靶向能力，用于MW热疗联合化疗。修饰后的TPP显著增强了敏化剂靶向线粒体（细胞中对热敏感的能量供应细胞器）的特异性。因此，PLGA纳米球中负载的Gd所诱导的MW热损伤也得到了加强。此外，由于Gd的存在，该系统还能够实现MR成像。另外，包裹的Dtxl发挥抑制线粒体功能的化疗作用，以辅助MW热疗。实验表明，PLGA具有高生物相容性，即使剂量高达200 mg/kg也不会产生明显损伤。同时，代表线粒体靶向与MW热疗-化疗相结合的DGPPT+MW也已被证明能有效缩小肿瘤大小。本研究为构建具有主动靶向能力、生物安全且多功能的MW敏化剂以抑制肿瘤生长提供了新方向。
