Hyperthermia-triggered drug delivery from iRGD-modified temperature-sensitive liposomes enhances the anti-tumor efficacy using high intensity focused ultrasound

• Published in: Journal of controlled release 2016-12, Vol.243, p.333-341
• Main Authors: Deng, Zhiting, Xiao, Yang, Pan, Min, Li, Fei, Duan, Wanlu, Meng, Long, Liu, Xin, Yan, Fei, Zheng, Hairong
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacokinetics; Cell Line, Tumor; Doxorubicin - administration & dosage; Doxorubicin - pharmacokinetics; Drug Delivery Systems; High intensity focused ultrasound; High-Intensity Focused Ultrasound Ablation - methods; Hot Temperature; Humans; iRGD; Liposomes; Mice; Mice, Inbred BALB C; Nanoparticles; Neoplasms - drug therapy; Neoplasms - pathology; Oligopeptides - chemistry; Targeted nanomedicine; Thermo-sensitive liposomes; Tissue Distribution; Triggered release
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2016.10.030

An important limitation to successful cancer treatment with chemotherapeutics is the inability to achieve therapeutically effective drug concentrations while avoiding healthy tissue damage. In this work, a new tumor-targeting peptide iRGD (CCRGDKGPDC) was used to modify drug-loaded low temperature-sensitive liposomes (iRGD-LTSL-DOX) to explore the anti-tumor effects in combination with high intensity focused ultrasound (HIFU) in vitro and in vivo. iRGD-LTSL-DOX can specifically target to ανβ3-positive cells and locally release the encapsulated doxorubicin (DOX) in a hyperthermia-triggered manner. In vivo results showed that DOX from iRGD-LTSL-DOX was intravascularly released and rapidly penetrated into tumor interstitial space after HIFU-triggered heat treatment, thereby overcoming the limited tumor penetration of anticancer drugs. Significantly stronger anti-tumor efficacy further supported the effective combination of iRGD-LTSL-DOX with HIFU-induced hyperthermia. Our study provided a novel tumor-targeting LTSL-DOX and demonstrated its usefulness in HIFU-induced hyperthermia-triggered drug delivery. [Display omitted]