GE11-Directed Functional Polymersomal Doxorubicin as an Advanced Alternative to Clinical Liposomal Formulation for Ovarian Cancer Treatment

• Published in: Molecular pharmaceutics 2018-09, Vol.15 (9), p.3664-3671
• Main Authors: Zou, Yan, Xia, Yifeng, Meng, Fenghua, Zhang, Jian, Zhong, Zhiyuan
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - therapeutic use; Cell Line, Tumor; Doxorubicin - analogs & derivatives; Doxorubicin - chemistry; Doxorubicin - therapeutic use; Drug Delivery Systems - methods; ErbB Receptors - metabolism; Female; Humans; Liposomes - chemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Ovarian Neoplasms - drug therapy; Peptides - chemistry; Polyethylene Glycols - chemistry; Polyethylene Glycols - therapeutic use; Random Allocation
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.8b00024

Ovarian cancer as a recurrent disease is often refractory to treatment including pegylated liposomal doxorubicin hydrochloride (Lipo-Dox). Here, GE11 peptide-modified reversibly cross-linked polymersomal doxorubicin (GE11-PS-Dox) was investigated as an advanced treatment for SKOV3 human ovarian tumors, which overexpress epidermal growth factor receptor (EGFR). The in vitro experiments using SKOV3 cancer cells demonstrated that GE11-PS-Dox induced obviously higher cellular uptake, Dox delivery to the nuclei, and antitumor activity than the nontargeted PS-Dox and Lipo-Dox controls. In vivo biodistribution experiments displayed 2.5-fold higher tumor accumulation for GE11-PS-Dox as compared to Lipo-Dox. Notably, GE11-PS-Dox could effectively suppress the progression of SKOV3 tumors and cause little adverse effects at 12 mg of Dox equiv/kg, leading to a remarkably increased survival rate of 100% over 78 days. In contrast, continued tumor growth and body weight loss were discerned for Lipo-Dox treated mice at 6 mg of Dox equiv/kg. Moreover, a single dose of GE11-PS-Dox at 60 mg of Dox equiv/kg showed also effective treatment and low toxicity toward SKOV3-tumor bearing mice. GE11-directed reversibly cross-linked polymersomal doxorubicin has emerged as an advanced alternative to Lipo-Dox for treatment of EGFR-overexpressing ovarian cancers.