Department of Biobank, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
Department of Pharmaceutics, Shenyang Pharmaceutical University, No.103, Wenhua Road, Shenyang, China.
Eur J Pharm Sci. 2022 Aug 1;175:106231. doi: 10.1016/j.ejps.2022.106231. Epub 2022 Jun 4.
The synergistic therapy of malignant tumors with chemotherapy and photothermal therapy has attracted extensive researcher attention. With the further development of photosensitizers, photosensitizer delivery and stability are the urgent problem to be solved at present. In this study, the biodegradable hybrid micelles (HMs) nano system for co-delivery paclitaxel (PTX) and IR825, investigating the photosensitizer stability in the drug delivery system and therapeutic effectiveness in vitro or in vivo. The hybrid micelle (PTX/IR825-TAT HMs) was self-assembled through hydrophobic interactions between polyethyleneimine-polycaprolactone (PEI-PCL) and TAT peptide modifided-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol) (TAT-PEG-DSPE). The results indicated that TAT HMs could successfully encapsulate IR825 PTX (PTX/IR825-TAT HMs). More importantly, IR825 encapsulated in hybrid micelles improved physiological stability, thermostability and photostability. In addition, the PTX released rapidly from PTX/IR825-TAT HMs in acidic and laser irradiation environments. In vitro cell analysis demonstrated that PTX/IR825-TAT HMs exhibited effective internalization of breast cancer cells. At the same time, PTX/IR825-TAT HMs with laser irradiation synergistically induced cancer cell apoptosis and death. indicating chemo-photothermal therapy synergistic therapeutic effect. In vivo antitumor studies showed that PTX/IR825-TAT HMs precisely reached the tumor tissue and convert light energy into heat energy under laser irradiation, PTX/IR825-TAT HMs had excellent synergistic antitumor efficiency compared to single chemotherapy and photothermal therapy.
化疗和光热疗法联合治疗恶性肿瘤引起了广泛的研究关注。随着光敏剂的进一步发展，目前亟待解决的问题是光敏剂的输送和稳定性。在这项研究中，我们构建了一种共载紫杉醇（PTX）和 IR825 的可生物降解杂化胶束（HM）纳米系统，研究了药物传递系统中光敏剂的稳定性和体外或体内的治疗效果。通过聚乙二胺-聚己内酯（PEI-PCL）与 TAT 肽修饰的 1,2-二硬脂酰基-sn-甘油-3-磷酸乙醇胺-N-（聚乙二醇）（TAT-PEG-DSPE）之间的疏水相互作用自组装形成杂化胶束（PTX/IR825-TAT HM）。结果表明，TAT HM 可以成功包载 IR825 和 PTX（PTX/IR825-TAT HM）。更重要的是，IR825 包载于杂化胶束中提高了生理稳定性、热稳定性和光稳定性。此外，在酸性和激光照射环境中，PTX/IR825-TAT HM 中 PTX 快速释放。体外细胞分析表明，PTX/IR825-TAT HM 对乳腺癌细胞具有有效的内化作用。同时，PTX/IR825-TAT HM 在激光照射下协同诱导癌细胞凋亡和死亡，表现出化疗-光热协同治疗效果。体内抗肿瘤研究表明，PTX/IR825-TAT HM 可以精确到达肿瘤组织，并在激光照射下将光能转化为热能，与单一化疗和光热治疗相比，PTX/IR825-TAT HM 具有优异的协同抗肿瘤效率。
