SPIO nanoparticle-stabilized PAA-F127 thermosensitive nanobubbles with MR/US dual-modality imaging and HIFU-triggered drug release for magnetically guided in vivo tumor therapy.
Nanobubbles can serve as promising, next-generation theranostic platforms for ultrasound (US) and magnetic resonance (MR) imaging, and combined magnetic targeting (MT) and high-intensity focused ultrasound (HIFU)-triggered drug release for tumor therapy. Nanobubble-based dual contrast enhancement agents encapsulated with perfluoropentane and stabilized with superparamagnetic iron oxide (SPIO) nanoparticles have been synthesized through a single-step emulsion process from thermosensitive F127 and polyacrylic acid (PAA). Both US and MR imaging contrast can be optimized by varying the shell thickness and SPIO-embedded concentration. The US contrast can be enhanced from a mean gray value of 62 to 115, and the MR r2 value can be enhanced from 164 to 208 (s(-1)mM (-1)Fe) by increasing the SPIO concentration from 14.1 to 28.2mg/mL, respectively. In vivo investigations of SPIO-embedded nanobubbles in excised tumors under external MT revealed that the US and MR signals change quantitatively compared to the same site without MT. This combined strategy enables the nanobubbles to enhance both passive targeting (increasing the permeability by HIFU) and physical MT of chemotherapeutic drugs to tumors. The integration of functionalities makes this nanobubble system a powerful and viable new tool to achieve simultaneous in vivo tumor imaging and efficacious cancer therapy.
Department of Materials Science and Engineering, National Chiao Tung University, No. 1001, Ta-Hsueh Rd., Hsinchu 300, Taiwan, ROC.
Hsin-Yang
HY
Huang
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan, ROC.
Shang-Hsiu
SH
Hu
Department of Materials Science and Engineering, National Chiao Tung University, No. 1001, Ta-Hsueh Rd., Hsinchu 300, Taiwan, ROC.
Shih-Ya
SY
Hung
Department of Materials Science and Engineering, National Chiao Tung University, No. 1001, Ta-Hsueh Rd., Hsinchu 300, Taiwan, ROC.
Chih-Sheng
CS
Chiang
Departments of Electrical Engineering, Chang-Gung University College of Medicine and Memorial Hospital, Taoyuan 333, Taiwan, ROC.
Hao-Li
HL
Liu
Department of Neurosurgery, Tzu Chi General Hospital, Tzu Chi University, No. 707, Sec. 3, Chung Yang Rd., Hualien 970, Taiwan, ROC.
Tsung-Lang
TL
Chiu
Department of Neurology, University of North Carolina at Chapel Hill, No.130 Mason Farm Rd., CB# 7513, Chapel Hill 27599, USA.
Hsin-Yi
HY
Lai
Department of Biomedical Engineering, National Yang Ming University, No.155, Sec. 2, Linong St., Taipei 112, Taiwan, ROC. Electronic address: youyin.chen@gmail.com.
You-Yin
YY
Chen
Department of Materials Science and Engineering, National Chiao Tung University, No. 1001, Ta-Hsueh Rd., Hsinchu 300, Taiwan, ROC. Electronic address: sanyuanchen@mail.nctu.edu.tw.
San-Yuan
SY
Chen
D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003287:Contrast Media / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles; D008958:Models, Molecular; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D011095:Polyethylenes / Q000737:chemistry; D011126:Polypropylenes / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014465:Ultrasonics / Q000379:methods
D000180:Acrylic Resins; D000970:Antineoplastic Agents; D003287:Contrast Media; D058185:Magnetite Nanoparticles; D011095:Polyethylenes; D011126:Polypropylenes; C006903:carbopol 940; C078661:UCON 50-HB-5100
Focus ultrasound; Magnetic targeting; Nanobubble; Superparamagnetic