title: Synergistic delivery of gold nanorods using multifunctional microbubbles for enhanced plasmonic photothermal therapy.
abstract: Plasmonic photothermal therapy (PPTT) using plasmonic nanoparticles as efficient photoabsorbing agents has been proposed previously. One critical step in PPTT is to effectively deliver gold nanoparticles into the cells. This study demonstrates that the delivery of gold nanorods (AuNRs) can be greatly enhanced by combining the following three mechanisms: AuNRs encapsulated in protein-shell microbubbles (AuMBs), molecular targeting, and sonoporation employing acoustic cavitation of microbubbles (MBs). Both in vitro and in vivo tests were performed. For molecular targeting, the AuMBs were modified with anti-VEGFR2. Once bound to the angiogenesis markers, the MBs were destroyed by ultrasound to release the AuNRs and the release was confirmed by photoacoustic measurements. Additionally, acoustic cavitation was induced during MB destruction for sonoporation (i.e., increase in transient cellular permeability). The measured inertial cavitation dose was positively correlated with the temperature increase at the tumor site. The quantity of AuNRs delivered into the cells was also determined by measuring the mass spectrometry and observed using third-harmonic-generation microscopy and two-photon fluorescence microscopy. A temperature increase of 20 °C was achieved in vitro. The PPTT results in vivo also demonstrated that the temperature increase (>45 °C) provided a sufficiently high degree of hyperthermia. Therefore, synergistic delivery of AuNRs was demonstrated.
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Hsin
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan.
authors.forename: Ai-Ho
authors.initials: AH
authors.lastname: Liao
authors.affiliation: Department of Chemistry and Biochemistry, National Chung-Cheng University, Chia-Yi, Taiwan.
authors.forename: Ya-Chuen
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Department of Chemistry and Biochemistry, National Chung-Cheng University, Chia-Yi, Taiwan.
authors.forename: Cheng-Ru
authors.initials: CR
authors.lastname: Lee
authors.affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Wu
authors.affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Biochemistry, National Chung-Cheng University, Chia-Yi, Taiwan.
authors.forename: Churng-Ren Chris
authors.initials: CR
authors.lastname: Wang
authors.affiliation: 1] Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan [2] Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Pai-Chi
authors.initials: PC
authors.lastname: Li
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D005260:Female; D006046:Gold / Q000008:administration & dosage*; D006801:Humans; D006979:Hyperthermia, Induced; D008546:Melanoma, Experimental / Q000628:therapy*; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D045423:Microbubbles / Q000627:therapeutic use*; D013010:Sonication; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D006046:Gold