title: Theranostic Liposomes with Hypoxia-Activated Prodrug to Effectively Destruct Hypoxic Tumors Post-Photodynamic Therapy.
abstract: Photodynamic therapy (PDT), a noninvasive cancer therapeutic method triggered by light, would lead to severe tumor hypoxia after treatment. Utilizing a hypoxia-activated prodrug, AQ4N, which only shows toxicity to cancer cells under hypoxic environment, herein, a multipurpose liposome is prepared by encapsulating hydrophilic AQ4N and hydrophobic hexadecylamine conjugated chlorin e6 (hCe6), a photosensitizer, into its aqueous cavity and hydrophobic bilayer, respectively. After chelating a64Cu isotope with Ce6, the obtained AQ4N-64Cu-hCe6-liposome is demonstrated to be an effective imaging probe for in vivo positron emission tomography, which together with in vivo fluorescence and photoacoustic imaging uncovers efficient passive homing of those liposomes after intravenous injection. After being irradiated with the 660 nm light-emitting diode light, the tumor bearing mice with injection of AQ4N-hCe6-liposome show severe tumor hypoxia, which in turn would trigger activation of AQ4N, and finally contributes to remarkably improved cancer treatment outcomes via sequential PDT and hypoxia-activated chemotherapy. This work highlights a liposome-based theranostic nanomedicine that could utilize tumor hypoxia, a side effect of PDT, to trigger chemotherapy, resulting in greatly improved efficacy compared to conventional cancer PDT.
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou 215123, China.|State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macau 999078, China.
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Feng
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou 215123, China.|Departments of Radiology and Medical Physics, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou 215123, China.
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou 215123, China.
authors.forename: Danlei
authors.initials: D
authors.lastname: Tao
authors.affiliation: Departments of Radiology and Medical Physics, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.affiliation: Departments of Radiology and Medical Physics, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macau 999078, China.
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou 215123, China.
authors.forename: Zhuang
authors.identifier: 0000-0002-1629-1039
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006838:Hydrocarbons / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D008081:Liposomes; D051379:Mice; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000068936:Theranostic Nanomedicine
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D006838:Hydrocarbons; D008081:Liposomes; D017319:Photosensitizing Agents; D011355:Prodrugs; C013553:hexadecylamine
keywords: hypoxia-activated therapy; liposomes; multimodal imaging; photodynamic therapy; tumor hypoxia