Novel self-micellizing anticancer lipid nanoparticles induce cell death of colorectal cancer cells.

Autor: Sundaramoorthy P; Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea., Baskaran R; Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea., Mishra SK; Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea; Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Central University, Sagar 470003, India., Jeong KY; Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea., Oh SH; Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea., Kyu Yoo B; Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea., Kim HM; Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, Republic of Korea. Electronic address: hwanmook@gachon.ac.kr.
Jazyk: angličtina
Zdroj: Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2015 Nov 01; Vol. 135, pp. 793-801. Date of Electronic Publication: 2015 Aug 28.
DOI: 10.1016/j.colsurfb.2015.08.039
Abstrakt: In the present study, we developed a novel drug-like self-micellizing anticancer lipid (SMAL), and investigated its anticancer activity and effects on cell death pathways in human colorectal cancer (CRC) cell lines. Three self-assembled nanoparticles were prepared, namely, SMAL102 (lauramide derivative), SMAL104 (palmitamide derivative), and SMAL108 (stearamide derivative) by a thin-film hydration technique, and were characterized for physicochemical and biological parameters. SMAL102 were nanosized (160.23 ± 8.11 nm) with uniform spherical shape, while SMAL104 and SMAL108 did not form spherical shape but formed large size nanoparticles and irregular in shape. Importantly, SMAL102 showed a cytotoxic effect towards CRC cell lines (HCT116 and HT-29), and less toxicity to a normal colon fibroblast cell line (CCD-18Co). Conversely, SMAL104 and SMAL108 did not have an anti-proliferative effect on CRC cell lines. SMAL102 nanoparticles were actively taken up by CRC cell lines, localized in the cell membrane, and exhibited remarkable cytotoxicity in a concentration-dependent manner. The normal colon cell line showed significantly less cellular uptake and non-cytotoxicity as compared with the CRC cell lines. SMAL102 nanoparticles induced caspase-3, caspase-9, and PARP cleavage in HT-29 cells, indicating the induction of apoptosis; whereas LC3B was activated in HCT116 cells, indicating autophagy-induced cell death. Collectively, these results demonstrate that SMAL102 induced cell death via activation of apoptosis and autophagy in CRC cell lines. The present study could be a pioneer for further preclinical and clinical development of such compounds.
(Copyright © 2015 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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