Oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer

Abstract

Purpose:The failure of cancer treatments is partly due to the enrichment of cancer stem-like cells (CSLCs) that are resistant to conventional chemotherapy. A novel micelle formulation of oxaliplatin (OXA) encapsulated in chitosan vesicle was developed. The authors postulate that micelle encapsulation of OXA would eliminate both CSLCs and bulk cancer cells in colorectal cancer (CRC). Experimental design: In this study, using stearic acid-g-chitosan oligosaccharide (CSO-SA) polymeric micelles as a drug-delivery system, OXA-loaded CSO-SA micelles (CSO-SA/OXA) were prepared. Intracellular uptake of CSO-SA/OXA micelles was assessed by confocal microscope. The effects of free OXA, the empty carrier, and CSO-SA/OXA micelles were tested using human CRC cell lines in vitro and in vivo. Results: The micelles showed excellent internalization ability that increased OXA accumulation both in CRC cells and tissues. Furthermore, CSO-SA/OXA micelles could either increase the cytotoxicity of OXA against the bulk cancer cells or reverse chemoresistance of CSLC subpopulations in vitro. Intravenous administration of CSO-SA/OXA micelles effectively suppressed the tumor growth and reduced CD133 + /CD24+ cell (putative CRC CSLC markers) compared with free OXA treatment, which caused CSLC enrichment in xenograft tumors (P , 0.05). Conclusion:The results of this study indicate that CSO-SA micelle as a drug-delivery carrier is effective for eradicating CSLCs and may act as a new option for CRC therapy.

Aspirin cooperates with p300 to activate the acetylation of H3K9 and promote FasL-mediated apoptosis of cancer stem-like cells in colorectal cancer

“…The majority of tumor cells lose their CSC properties during tumor growth in vivo. It has been reported that oxaliplatin treatment can enrich the TC /CSC 6 , 31 . We then employed oxaliplatin to enrich the CSCs and tested the effect of aspirin on them.…”

“…The majority of deaths from colorectal cancer are associated with tumor cell metastasis and resistance to chemotherapy 2 , 3 . Numerous studies have suggested that cancer stem-like cells (CSCs) mediate resistance to conventional therapies, drive tumor cell metastasis, and promote tumor recurrence in CRC 4 - 6 . Therefore, CSCs represent promising targets for effective prevention and treatment against colorectal cancer 7 .…”

Understanding the colon cancer stem cells and perspectives on treatment

“…Technologies such as antibody PEGylation [ 81 ] polysialylation [ 82 ] and albumin can be used to engineer a longer blood half-life for use against target signaling pathways and/or molecules that selective operate in CSCs, some of which are also capable of killing subpopulations of cancer cells that do not display CSC properties. Therapeutic approaches with mAbs [ 83 - 90 ], antibody constructs and novel therapeutic strategies against colon CSCs [ 91 , 92 ] are summarized in Table 1 , and some of these methods are reviewed in detail below.…”

“…For example, polymeric micelles with a core-shell structure can be formed by the self-aggregation of polymeric amphiphile for the delivery of cytotoxic agents after intravenous administration in solid tumors providing a significant advantage against tumor by increased the enhanced permeability and retention effect of the cytotoxic compounds [ 97 ]. A novel micelle formulation of oxaliplatin encapsulated in a chitosan vesicle (CSO-SA/OXA micelles) [ 92 ] shows an excellent internalization ability that targets the tumor cell nucleus and increases the oxaliplatin concentration in tumor cells, which was shown to eliminate CSCs in vitro and in vivo .…”

Prognostic role of CD133 expression in colorectal cancer: a meta-analysis

“…Increasing evidence suggests that cancers, including CRC, may be hierarchically organized, with only a small population of cancer cells, termed cancer stem cells (CSCs), possessing the potential to initiate and sustain tumor growth and metastasis [1-3]. Furthermore, these cells are inert to toxic environmental agents owing to their high expression of ABC transporters, resistance to apoptosis, and efficient DNA repair mechanisms [4-6].…”