期刊
ACS APPLIED MATERIALS & INTERFACES
卷 11, 期 45, 页码 42534-42548出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b11307
关键词
biomimetic delivery platform; an albumin-bound complex; gp60; SPARC; antitumor; antimetastasis
资金
- National Natural Science Foundation of China [81872807]
- Sichuan Major Science and Technology Project on Biotechnology and Medicine [2018SZDZX0018]
- Fundamental Research Funds for the Central Universities [2017SCU12062]
- China Postdoctoral Science Foundation [2017M623051]
Biomimetic design has been extensively investigated. The only FDA-approved biomimetic albumin-bound paclitaxel may not be beneficial to some treated patients due to rapid dissociation upon intravenous infusion and no substantial improvement in the drug's pharmacokinetics or biodistribution. Herein, we developed an alternative and injectable preformed albumin-bound anticancer drug delivery. We combined HSA, Kolliphor HS 15 (HS15), and pirarubicin (THP) via purely physical forces in a thin-film hydration method to obtain an albumin-bound complex of HSA-THP. The lack of any chemical reactions preserves HSA bioactivity, in contrast to the destroyed secondary structure within AN-THP (albumin nanoparticle of THP) for the harsh manipulation during preparation. In vitro, HSA-THP showed a significantly higher cellular uptake efficiency than THP, and the complex was more cytotoxic. In vivo, HSA-THP showed longer half-life than THP. It also exhibited greater tumor accumulation and tumor penetration via gp60- and SPARC-mediated biomimetic transport than THP and AN-THP. As a result, HSA-THP showed strong antitumor and antimetastasis efficacy, with relatively little toxicity. These results suggest the clinical potential of biomimetic tumor-targeted drug delivery.
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