공민석 (National Institutes of Health, 서울과학기술대학교) | 한빛사논문 > 한빛사

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조회716

National Institutes of Health, 서울과학기술대학교

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Cell Reports, 2023 Jan 31;42(1):111955 | https://doi.org/10.1016/j.celrep.2022.111955 Cell-specific cargo delivery using synthetic bacterial spores

Minsuk Kong ^1,2,6, Domenico D’Atri ^1,6, Maria Teresa Bilotta¹, Bailey Johnson³, Taylor B. Updegrove ¹, Devorah L. Gallardo ⁴, Federico Machinandiarena ¹, I-Lin Wu ¹, Maira Alves Constantino ³, Stephen M. Hewitt ⁵, Kandice Tanner ³, David J. Fitzgerald¹, Kumaran S. Ramamurthi ^1,7

¹Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
²Department of Food Science and Technology, Seoul National University of Science and Technology, Seoul 01811, South Korea
³Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
⁴Laboratory Animal Sciences Program, Leidos Biomedical Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
⁵Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
⁶These authors contributed equally
⁷Lead contact

Corresponding authors: Kandice Tanner, David J. Fitzgerald, Kumaran S. Ramamurthi

Abstract

Delivery of cancer therapeutics to non-specific sites decreases treatment efficacy while increasing toxicity. In ovarian cancer, overexpression of the cell surface marker HER2, which several therapeutics target, relates to poor prognosis. We recently reported the assembly of biocompatible bacterial spore-like particles, termed "SSHELs." Here, we modify SSHELs with an affibody directed against HER2 and load them with the chemotherapeutic agent doxorubicin. Drug-loaded SSHELs reduce tumor growth and increase survival with lower toxicity in a mouse tumor xenograft model compared with free drug and with liposomal doxorubicin by preferentially accumulating in the tumor mass. Target cells actively internalize and then traffic bound SSHELs to acidic compartments, whereupon the cargo is released to the cytosol in a pH-dependent manner. We propose that SSHELs represent a versatile strategy for targeted drug delivery, especially in cancer settings.

논문정보

형식Research article
게재일2023년 01월 (BRIC 등록일 2023-02-16)
연구진국내+국외 연구진
분야 생명과학 > 식품학

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