title: A FRET-guided, NIR-responsive bubble-generating liposomal system for in vivo targeted therapy with spatially and temporally precise controlled release.
abstract: The nonspecific distribution of therapeutic agents and nontargeted heating commonly produce undesirable side effects during cancer treatment since the optimal timing of triggering the carrier systems is unknown. This work proposes a multifunctional liposomal system that can intracellularly and simultaneously deliver the therapeutic drug doxorubicin (DOX), heat, and a bubble-generating agent (ammonium bicarbonate, ABC) into targeted tumor cells to have a cytotoxic effect. Gold nanocages that are encapsulated in liposomes effectively convert near-infrared light irradiation into localized heat, which causes the decomposition of ABC and generates CO2 bubbles, rapidly triggering the release of DOX. Additionally, a hybridized Mucin-1 aptamer is conjugated on the surface of the test liposomes, which then function as a recognition probe to enhance the uptake of those liposomes by cells, and as a molecular beacon to signal when the internalized particles have been maximized, which is the optimal time for photothermally triggering the release of the drug following the systemic administration of the liposomes. Empirical results reveal that this combined treatment effectively controls targeted drug release in a spatially and temporally precise fashion and so significantly increases the potency of the drug while minimizing unwanted side effects, making it a promising treatment for cancer.
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Chuang
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Ko-Jie
authors.initials: KJ
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: De-Hui
authors.initials: DH
authors.lastname: Wan
authors.affiliation: Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan, ROC; Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung University, Taoyuan 33305, Taiwan, ROC.
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.affiliation: Department of Bioagriculture, National Chiayi University, Chiayi 60004, Taiwan, ROC.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Ho
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Po-Yen
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC; Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC. Electronic address: hwsung@mx.nthu.edu.tw.
authors.forename: Hsing-Wen
authors.initials: HW
authors.lastname: Sung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004705:Endocytosis; D005453:Fluorescence; D031541:Fluorescence Resonance Energy Transfer; D056945:Hep G2 Cells; D006801:Humans; D007259:Infrared Rays; D008081:Liposomes / Q000737:chemistry*; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D056004:Molecular Dynamics Simulation; D057054:Molecular Imaging; D053758:Nanoparticles / Q000737:chemistry; D013696:Temperature; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D008081:Liposomes; D004317:Doxorubicin
keywords: Cancer therapy; Gold nanocage; Molecular beacon; Photothermal effect; Targeted delivery