Selective intracellular vaporisation of antibody-conjugated phase-change nano-droplets in vitro.
While chemotherapy is a major mode of cancer therapeutics, its efficacy is limited by systemic toxicities and drug resistance. Recent advances in nanomedicine provide the opportunity to reduce systemic toxicities. However, drug resistance remains a major challenge in cancer treatment research. Here we developed a nanomedicine composed of a phase-change nano-droplet (PCND) and an anti-cancer antibody (9E5), proposing the concept of ultrasound cancer therapy with intracellular vaporisation. PCND is a liquid perfluorocarbon nanoparticle with a liquid-gas phase that is transformable upon exposure to ultrasound. 9E5 is a monoclonal antibody targeting epiregulin (EREG). We found that 9E5-conjugated PCNDs are selectively internalised into targeted cancer cells and kill the cells dynamically by ultrasound-induced intracellular vaporisation. In vitro experiments show that 9E5-conjugated PCND targets 97.8% of high-EREG-expressing cancer cells and kills 57% of those targeted upon exposure to ultrasound. Furthermore, direct observation of the intracellular vaporisation process revealed the significant morphological alterations of cells and the release of intracellular contents.
Department of Precision Engineering, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
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Ishijima
Department of Applied Chemistry, Kyushu University, Fukuoka 819-0395, Japan.|Department of Chemistry &Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
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Minamihata
Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan.
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Yamaguchi
Department of Chemistry &Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
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Yamahira
Department of Precision Engineering, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
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Ichikawa
Department of Precision Engineering, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
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Kobayashi
Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan.
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Iijima
Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan.
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Shibasaki
Center for Disease Biology and Integrative Medicine, The University of Tokyo, Tokyo 113-8656, Japan.
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Azuma
Department of Chemistry &Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.|Department of Bioengineering, The University of Tokyo, Tokyo 113-8656, Japan.
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Nagamune
Department of Precision Engineering, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.|Department of Bioengineering, The University of Tokyo, Tokyo 113-8656, Japan.|Medical Device Development and Regulation Research Center, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
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Sakuma
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D066260:Epiregulin / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D008807:Mice, Inbred BALB C; D058726:Nanoconjugates; D050997:Nanomedicine; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014464:Ultrasonic Therapy / Q000295:instrumentation / Q000379:methods*
D000911:Antibodies, Monoclonal; D016588:Anticarcinogenic Agents; C587880:EREG protein, human; D066260:Epiregulin; D058726:Nanoconjugates