Jin Yushen, Liang Xiaolong, An Yunkun, Dai Zhifei
Department of Biomedical Engineering, College of Engineering, Peking University , Beijing 100871, China.
Bioconjug Chem. 2016 Dec 21;27(12):2931-2942. doi: 10.1021/acs.bioconjchem.6b00603. Epub 2016 Nov 27.
The microwave and temperature sensitive liposomes were fabricated successfully from 1,2-dipalmityol-sn-glycero-3-phosphocholine (DPPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG) with a molar ratio of 4:1:0.26 by co-encapsulating NaCl and doxorubicin (DOX) through the thin-film hydration method to externally manipulate drug release at a predetermined location in the body at a desired time in the right dosage for combination microwave hyperthermia and chemotherapy of cancer to afford a synergistic therapeutic effect. It was found that the confinement of the high concentration of NaCl ions inside the small size of the liposomes led to a more-rapid temperature elevation than the dissociative ions upon microwave treatment. More than 67.6% doxorubicin was released from the DOX and NaCl co-loaded liposomes (DOX&NaCl@liposomes) upon microwave irradiation for 2 min. After incubation with 2 mg/mL DOX&NaCl@liposomes for 4 h followed by treatment with microwave for 2 min, the inhibition rate of human breast cancer cell MDA-MB-231 was evaluated as 76.1%, much higher than that for NaCl@liposomes (29.8%) and DOX@liposomes (40.2%). The tumor growth inhibition was evaluated to be 73.4% after intravenous injection of DOX&NaCl@liposomes followed by microwave irradiation, much higher than that with only NaCl@liposomes (41.5%) or DOX@liposomes (45.5%) combined with microwave irradiation. Therefore, DOX&NaCl@liposomes could serve as a promising thermochemotherapy nanomedicine for cancer treatment because of its excellent microwave susceptible property and good biocompatibility.
通过薄膜水化法，以摩尔比4:1:0.26的1,2 - 二棕榈酰 - sn - 甘油 - 3 - 磷酸胆碱（DPPC）、胆固醇和1,2 - 二硬脂酰 - sn - 甘油 - 3 - 磷酸乙醇胺 - N - [甲氧基（聚乙二醇）- 2000]（DSPE - PEG）成功制备了微波和温度敏感脂质体，共包封氯化钠（NaCl）和阿霉素（DOX），以便在体内预定位置、在期望时间以合适剂量从外部控制药物释放，用于癌症的联合微波热疗和化疗，以产生协同治疗效果。研究发现，脂质体小尺寸内高浓度NaCl离子的限制导致微波处理时比解离离子温度升高更快。微波照射2分钟后，超过67.6%的阿霉素从共载DOX和NaCl的脂质体（DOX&NaCl@脂质体）中释放。用2 mg/mL DOX&NaCl@脂质体孵育4小时后再微波处理2分钟，人乳腺癌细胞MDA - MB - 231的抑制率评估为76.1%，远高于NaCl@脂质体（29.8%）和DOX@脂质体（40.2%）。静脉注射DOX&NaCl@脂质体后进行微波照射，肿瘤生长抑制率评估为73.4%，远高于单独使用NaCl@脂质体（41.5%）或DOX@脂质体（45.5%）联合微波照射。因此，DOX&NaCl@脂质体因其优异的微波敏感性和良好的生物相容性，可作为一种有前景的癌症热化疗纳米药物。
