期刊
NANOMEDICINE
卷 17, 期 10, 页码 717-739出版社
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2022-0010
关键词
anticancer activity; CXCR-4-targeting; dinoflagellates; passive targeting; pH-sensitive nanoliposomes; prostate and breast cancer treatment; yessotoxin
资金
- Nanotechnology-Based Functional Solutions - North Portugal Regional Operational Programme (NORTE2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF) [NORTE-01-0145-FEDER-000019]
- Marie Sklodowska-Curie Actions from European Union [600375]
- Fundacao para a Ciencia e Tecnologia [UID/BIA/04050/2020]
- Fundo Regional for Ciencia e Tecnologia da Regiao Autonoma dos Acores [M3.1.a/F/128/2015]
This study developed nanoliposomes targeting chemokine receptor CXCR-4, which showed high cytotoxicity towards cancer cells while protecting normal cells. The acid pH-induced fusion of nanoliposomes was found to be the primary pathway for cellular internalization.
Background: Yessotoxin (YTX), a marine-derived drug, was encapsulated in PEGylated pH-sensitive nanoliposomes, covalently functionalized (strategy I) with SDF-1 alpha and by nonspecific adsorption (strategy II), to actively target chemokine receptor CXCR-4. Methods: Cytotoxicity to normal human epithelial cells (HK-2) and prostate (PC-3) and breast (MCF-7) adenocarcinoma models, with different expression levels of CXCR-4, were tested. Results: Strategy II exerted the highest cytotoxicity toward cancer cells while protecting normal epithelia. Acid pH-induced fusion of nanoliposomes seemed to serve as a primary route of entry into MCF-7 cells but PC-3 data support an endocytic pathway for their internalization. Conclusion: This work describes an innovative hallmark in the current marine drug clinical pipeline, as the developed nanoliposomes are promising candidates in the design of groundbreaking marine flora-derived anticancer nanoagents.
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