Liao JinFeng, Li WenTing, Peng JinRong, Yang Qian, Li He, Wei YuQuan, Zhang XiaoNing, Qian ZhiYong
1. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
2. School of Medical and Life Sciences, University of Jinan, Jinan 250022, PR China.
Theranostics. 2015 Jan 20;5(4):345-56. doi: 10.7150/thno.10731. eCollection 2015.
Gold nanorods (GNRs) are well known in photothermal therapy based on near-infrared (NIR) laser absorption of the longitudinal plasmon band. Herein, we developed an effective stimulus system -- GNRs and doxorubicin co-loaded polymersomes (P-GNRs-DOX) -- to facilitate co-therapy of photothermal and chemotherapy. DOX can be triggered to release once the polymersomes are corrupted under local hyperthermic condition of GNRs induced by NIR laser irradiation. Also, the cytotoxicity of GNRs caused by the residual cetyltrimethylacmmonium bromide (CTAB) was reduced by shielding the polymersomes. The GNRs-loaded polymersomes (P-GNRs) can be efficiently taken up by the tumor cells. The distribution of the nanomaterial was imaged by IR-820 and quantitatively analyzed by ICP-AES. We studied the ablation of tumor cells in vitro and in vivo, and found that co-therapy offers significantly improved therapeutic efficacy (tumors were eliminated without regrowth.) compared with chemotherapy or photothermal therapy alone. By TUNEL immunofluorescent staining of tumors after NIR laser irradiation, we found that the co-therapy showed more apoptotic tumor cells than the other groups. Furthermore, the toxicity study by pathologic examination of the heart tissues demonstrated a lower systematic toxicity of P-GNRs-DOX than free DOX. Thus, the chemo-photothermal treatment based on polymersomes loaded with DOX and GNRs is a useful strategy for maximizing the therapeutic efficacy and minimizing the dosage-related side effects in the treatment of solid tumors.
金纳米棒(GNRs)在基于近红外(NIR)激光吸收纵向等离子体激元带的光热疗法中广为人知。在此,我们开发了一种有效的刺激系统——金纳米棒和阿霉素共负载聚合物囊泡(P-GNRs-DOX)——以促进光热和化疗的联合治疗。一旦聚合物囊泡在近红外激光照射诱导的金纳米棒局部热疗条件下被破坏,阿霉素就会被触发释放。此外,通过对聚合物囊泡进行屏蔽,降低了由残留的十六烷基三甲基溴化铵(CTAB)引起的金纳米棒的细胞毒性。负载金纳米棒的聚合物囊泡(P-GNRs)能够被肿瘤细胞有效摄取。通过IR-820对纳米材料的分布进行成像,并通过电感耦合等离子体原子发射光谱法(ICP-AES)进行定量分析。我们研究了肿瘤细胞在体外和体内的消融情况,发现与单独的化疗或光热疗法相比,联合治疗具有显著提高的治疗效果(肿瘤被消除且无复发)。通过对近红外激光照射后的肿瘤进行TUNEL免疫荧光染色,我们发现联合治疗组的凋亡肿瘤细胞比其他组更多。此外,通过对心脏组织进行病理检查的毒性研究表明,P-GNRs-DOX的全身毒性低于游离阿霉素。因此,基于负载阿霉素和金纳米棒的聚合物囊泡的化学-光热治疗是一种在实体瘤治疗中最大化治疗效果并最小化剂量相关副作用的有用策略。
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