title: Multifunctional theranostic contrast agent for photoacoustics- and ultrasound-based tumor diagnosis and ultrasound-stimulated local tumor therapy.
abstract: Biomedical imaging-guided cancer therapy should have capabilities of both accurate tumor diagnosis and high therapeutic efficacy for the personalized treatment. Various biomedical imaging-guided cancer therapies are currently being investigated to overcome current limitations that include low sensitivity of diagnosis and poor drug delivery to the tumor site. Here, we report the development of a multifunctional theranostic contrast agent demonstrating high sensitive photoacoustic and ultrasound imaging and effective local delivery of anticancer drug to a tumor site. A microbubble (porphyrin-MB) was developed using phospholipid-porphyrin conjugates to enhance ultrasound and photoacoustic signal intensities simultaneously. Paclitaxel-loaded human serum albumin nanoparticles (PTX-HSA-NPs) were then conjugated onto the surface of the microbubble. The developed PTX-HSA-NPs conjugated porphyrin-MB (porphyrin-MB-NPs) provided sensitive, dual modal images of a tumor at 700 nm optimal laser wavelength for photoacoustic imaging and 5-14 MHz operating frequency for the ultrasound imaging. In addition, porphyrin-MB-NPs efficiently suppressed tumor growth by ultrasound exposure. Exposure to the focused ultrasound triggered the collapse of porphyrin-MB-NPs, resulting in the local release of PTX-HSA-NPs and enhanced penetration into the tumor site. The increased preferential accumulation and penetration of PTX-HSA-NPs suppressed tumor growth 10-fold more than without exposure to ultrasound. In conclusion, the developed porphyrin-MB-NPs establish a new paradigm in simultaneous bi-functional ultrasound/photoacoustic imaging diagnosis and locally triggered release of nanomedicine and enhanced chemotherapy efficiency.
authors.affiliation: Department of Chemical & Biomolecular Engineering, Sogang University, #1 Sinsu-dong, Mapo-gu, Seoul 121-742, Republic of Korea.
authors.forename: Hyungwon
authors.initials: H
authors.lastname: Moon
authors.affiliation: Interdisciplinary program of Integrated Biotechnology, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 121-742, South Korea.
authors.forename: Jeeun
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Chemical & Biomolecular Engineering, Sogang University, #1 Sinsu-dong, Mapo-gu, Seoul 121-742, Republic of Korea.
authors.forename: Changbeom
authors.initials: C
authors.lastname: Sim
authors.affiliation: Department of Chemical & Biomolecular Engineering, Sogang University, #1 Sinsu-dong, Mapo-gu, Seoul 121-742, Republic of Korea.
authors.forename: Jamin
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Chemical & Biomolecular Engineering, Sogang University, #1 Sinsu-dong, Mapo-gu, Seoul 121-742, Republic of Korea.
authors.forename: Hohyeon
authors.initials: H
authors.lastname: Lee
authors.affiliation: Interdisciplinary program of Integrated Biotechnology, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 121-742, South Korea; Sogang Institutes of Advanced Technology, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 121-742, South Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Department of Chemical & Biomolecular Engineering, Sogang University, #1 Sinsu-dong, Mapo-gu, Seoul 121-742, Republic of Korea; Interdisciplinary program of Integrated Biotechnology, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 121-742, South Korea. Electronic address: hyuncheol@sogang.ac.kr.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Kim
mesh_terms: D000162:Acoustics; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007834:Lasers; D008807:Mice, Inbred BALB C; D045423:Microbubbles; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011166:Porphyrins / Q000008:administration & dosage* / Q000737:chemistry; D012709:Serum Albumin / Q000008:administration & dosage* / Q000737:chemistry; D000068936:Theranostic Nanomedicine; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; D011166:Porphyrins; D012709:Serum Albumin; D017239:Paclitaxel
keywords: Local tumor treatment; Photoacoustics; Theranostics; Ultrasound; Ultrasound-triggered release