title: Hyperthermia-triggered drug delivery from iRGD-modified temperature-sensitive liposomes enhances the anti-tumor efficacy using high intensity focused ultrasound.
abstract: 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.
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China; Shenzhen Key Laboratory of Nanobiomechanics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China.
authors.forename: Zhiting
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Pan
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Wanlu
authors.initials: W
authors.lastname: Duan
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Meng
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China. Electronic address: fei.yan@siat.ac.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China; Shenzhen Key Laboratory of Nanobiomechanics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China. Electronic address: hr.zheng@siat.ac.cn.
authors.forename: Hairong
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006358:Hot Temperature; D006801:Humans; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; C569656:N-end cysteine peptide tumor-homing peptide; D009842:Oligopeptides; D004317:Doxorubicin
keywords: High intensity focused ultrasound; Targeted nanomedicine; Thermo-sensitive liposomes; Triggered release; iRGD