Engineering of caveolae-specific self-micellizing anticancer lipid nanoparticles to enhance the chemotherapeutic efficacy of oxaliplatin in colorectal cancer cells.
作者： Pasupathi Sundaramoorthy , Thiruganesh Ramasamy , Siddhartha Kumar Mishra , Keun-Yeong Jeong , Chul Soon Yong
DOI: 10.1016/J.ACTBIO.2016.07.006
关键词: HT29 Cells 、 Drug delivery 、 Cancer research 、 PI3K/AKT/mTOR pathway 、 Intrinsic apoptotic signaling pathway 、 Nanocarriers 、 Cancer cell 、 Pharmacology 、 Biology 、 Endocytosis 、 Caveolae
摘要: Abstract Novel nanomaterials for the intracellular transport of therapeutic cargos have been actively sought to effectively breach cell-membrane barriers. In this study we developed novel self-micellizing anticancer lipid (SMAL)-based pro-apoptotic nanoparticles (NPs) that enhance accumulation and chemotherapeutic efficacy oxaliplatin (OL) in colorectal cancer cells (CRCs). We demonstrated NPs with special affinity caveolae could be designed based on specificity, differentiated between endothelial (tumor cells) epithelial cells, without need a cell-specific targeting moiety. remarkable uptake OL-loaded SMAL (SMAL-OL) HCT116 HT-29 via caveolae-mediated endocytosis (CvME) pathway. The higher SMAL-OL environment resulted significantly elevated effect compared free OL. Cell cycle analysis proved G2/M phase arrest, along substantial presence sub-G1 phase. An immunoblot indicated an upregulation markers (Bax; caspase-3; caspase-9; PARP1) downregulation Bcl-xl PI3K/AKT/mTOR complex, indicating possible intrinsic apoptotic signaling Overall, ability confer preferential specificity towards cell surface domain offer exciting means targeted delivery receptor-ligand-type strategies. Statement Significance work, cells. realized addition, oxaliplatin-loaded were efficiently endocytosed by represent significant breakthrough as effective drug system promising potential therapy. believe work holds development next generation multifunctional nanocarriers
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