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

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-s...

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Bibliographic Details
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
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Summary: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]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2016.10.030