title: Molecular imaging-guided photothermal/photodynamic therapy against tumor by iRGD-modified indocyanine green nanoparticles.
abstract: Multifunctional near-infrared (NIR) nanoparticles demonstrate great potential in tumor theranostic applications. To achieve the sensitive detection and effective phototherapy in the early stage of tumor genesis, it is highly desirable to improve the targeting of NIR theranostic agents to biomarkers and to enhance their accumulation in tumor. Here we report a novel targeted multifunctional theranostic nanoparticle, internalized RGD (iRGD)-modified indocyanine green (ICG) liposomes (iRGD-ICG-LPs), for molecular imaging-guided photothermal therapy (PTT) and photodynamic therapy (PDT) therapy against breast tumor. The iRGD peptides with high affinity to αvβ3 integrin and effective tumor-internalized property were firstly used to synthesize iRGD-PEG2000-DSPE lipopeptides, which were further utilized to fabricate the targeted ICG liposomes. The results indicated that iRGD-ICG-LPs exhibited excellent stability and could provide an accurate and sensitive detection of breast tumor through NIR fluorescence molecular imaging. We further employed this nanoparticle for tumor theranostic application, demonstrating significantly higher tumor accumulation and tumor inhibition efficacy through PTT/PDT effects. Histological analysis further revealed much more apoptotic cells, confirming the advantageous anti-tumor effect of iRGD-ICG-LPs over non-targeted ICG-LPs. Notably, the targeting therapy mediated by iRGD provides almost equivalent anti-tumor efficacy at a 12.5-fold lower drug dose than that by monoclonal antibody, and no tumor recurrence and obvious treatment-induced toxicity were observed in our study. Our study provides a promising strategy to realize the sensitive detection and effective treatment of tumors by integrating molecular imaging into PTT/PDT therapy.
authors.affiliation: Department of Ultrasonography, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics Guangdong Province), Guangzhou 510630, China; 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, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.affiliation: Department of Ultrasonography, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics Guangdong Province), Guangzhou 510630, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Ultrasonography, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics Guangdong Province), Guangzhou 510630, China. Electronic address: lmeihong@fimmu.com.
authors.forename: Hongmei
authors.initials: H
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, China.
authors.forename: Zhiting
authors.initials: Z
authors.lastname: Deng
authors.affiliation: The Department of Echocardiography, Clinical Center of Reproductive Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Ultrasound Department, Guangzhou General Hospital, Guangzhou Command, Guangzhou 510630, China.
authors.forename: Wanlu
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Ultrasonography, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics Guangdong Province), Guangzhou 510630, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Ultrasonography, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics Guangdong Province), Guangzhou 510630, China; 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, China. Electronic address: hr.zheng@siat.ac.cn.
authors.forename: Hairong
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival; D004396:Coloring Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D007208:Indocyanine Green / Q000493:pharmacokinetics / Q000627:therapeutic use*; D039302:Integrin alphaVbeta3 / Q000008:administration & dosage / Q000627:therapeutic use; D008081:Liposomes; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles; D009842:Oligopeptides / Q000627:therapeutic use*; D010778:Photochemotherapy / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared; D000068936:Theranostic Nanomedicine; D014018:Tissue Distribution
chemical_list: D004396:Coloring Agents; D039302:Integrin alphaVbeta3; D008081:Liposomes; C569656:N-end cysteine peptide tumor-homing peptide; D009842:Oligopeptides; D011092:Polyethylene Glycols; D007208:Indocyanine Green
keywords: Imaging-guided therapy; Indocyanine green; Phototherapy; Theranostic nanoparticles; iRGD