Co-delivery of doxorubicin and curcumin via cRGD-peptide modified PEG-PLA self-assembly nanomicelles for lung cancer therapy

• Published in: Chinese chemical letters Vol. 33; no. 5; pp. 2507 - 2511
• Main Authors: Zhang, Yunchu, Li, Tingting, Hu, Yuzhu, Chen, Jing, He, Yihong, Gao, Xiang, Zhang, Yan
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.05.2022; Department of Neurosurgery and Institute of Neurosurgery,State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,West China Medical School,Sichuan University and Collaborative Innovation Center for Biotherapy,Chengdu 610041,China%Department of Neurosurgery and Institute of Neurosurgery,State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,West China Medical School,Sichuan University and Collaborative Innovation Center for Biotherapy,Chengdu 610041,China%Department of Thoracic Oncology,Cancer Center,State Key Laboratory of Biotherapy,West China Hospital,West China Medical School,Sichuan University and Collaborative Innovation Center for Biotherapy,Chengdu 610041,China; Department of Thoracic Oncology,Cancer Center,State Key Laboratory of Biotherapy,West China Hospital,West China Medical School,Sichuan University and Collaborative Innovation Center for Biotherapy,Chengdu 610041,China
• Subjects: Co-delivery; Curcumin; Doxorubicin; Lung cancer; Nanomicelle; Nanomicelle; Curcumin; Co-delivery; Doxorubicin; Lung cancer
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2021.11.076

Lung cancer is the most common malignancy in the world, with a high mortality rate. Nevertheless, therapies to act effectively against lung cancer remain elusive. So far, chemotherapy is still the frontline treatment of lung cancer. Doxorubicin (DOX) is a broad-spectrum anti-tumor drug. However, DOX often has serious side effects and causes multi-drug resistance, which greatly limits its clinical application. In this work, biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) and cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) polypeptide modified PEG-PLA (cRGD-PEG-PLA) copolymers were used for the co-delivery of curcumin (CUR) and DOX (CUR-DOX/cRGD-M). The particle size of the self-assembled drug-loaded nanomicelle approximately was 27.4 nm and the zeta potential was −2.7 mV. Interestingly, CUR can enhance the uptake of DOX by Lewis lung carcinoma (LL/2) cells. The experimental results in vivo and in vitro showed that CUR-DOX/cRGD-M combination therapy could promote apoptosis of lung cancer cells, and conspicuously inhibit the tumor growth. Our data indicate that CUR-DOX/cRGD-M will be biodegradable and sustainable, which may have potential clinical application value in the treatment of lung cancer. Self-assembled nanocomposites composed of MPEG-PLA polymer, cRGD-PEG-PLA polymer, curcumin (CUR) and doxorubicin (DOX) were injected intravenously into Lewis lung carcinoma (LL/2) tumor-bearing mice, which showed remarkable ability of promoting tumor apoptosis, inhibiting tumor proliferation and inhibiting tumor angiogenesis. [Display omitted]