CD133-targeted delivery of self-assembled PEGylated carboxymethylcellulose-SN38 nanoparticles to colorectal cancer

Alibolandi, M. and Abnous, K. and Anvari, S. and Mohammadi, M. and Ramezani, M. and Taghdisi, S. M. (2018) CD133-targeted delivery of self-assembled PEGylated carboxymethylcellulose-SN38 nanoparticles to colorectal cancer. Artificial Cells, Nanomedicine and Biotechnology, 46 (sup1). pp. 1159-1169.

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Abstract

Poor aqueous solubility of chemotherapeutics such as SN38 (7-ethyl-10-hydroxycamptothecin) and the associated systemic adverse effects are serious limitations of their clinical use. To improve the drug delivery efficiency of such compounds, they were covalently conjugated to hydrophilic macromolecular carriers that specifically deliver the drug moiety to the tumour cells. In the current study, we developed a PEGylated acetylated carboxymethylcellulose conjugate of SN38 which was covalently attached to an aptamer against a cancer stem cell marker, CD133. Then, the designed nanoplatform was used to specifically deliver SN38 to colorectal cancer cells. The results demonstrated that the synthesized conjugate was self-assembled to nanoparticles with 169 nm in size and poly dispersity index of 0.11. Besides, the targeted self-assembled nanoparticles could significantly enhance the cellular uptake by CD133-expressing HT29 cell line confirmed by fluorescent microscopy and flow cytometry. Moreover, our results revealed that the targeted self-assembled nanoconjugate exhibited significantly lower IC 50 in HT29 cells overexpressing CD133 compared to non-targeted self-assembled nanoconjugate. The promising data suggest that the prepared targeted self-assembled drug conjugate nanoparticles possess the potential to offer the desirable physicochemical properties thereby enhancing the solubility and the therapeutic index of poorly soluble cytotoxic agents. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.

Item Type: Article
Additional Information: Cited By :6 Export Date: 16 February 2020 Correspondence Address: Ramezani, M.; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesIran; email: Ramezanim@mums.ac.ir
Uncontrolled Keywords: cancer stem cell carboxymethylcellulose CD133 colorectal cancer self-assemble SN38 Cell culture Controlled drug delivery Diseases Nanoconjugates Nanoparticles Solubility Stem cells Synthesis (chemical) Cancer stem cells Carboxy methylcellulose Targeted drug delivery aptamer CD133 antigen firtecan nanoconjugate self assembled monolayer drug carrier irinotecan macrogol nanoparticle animal cell animal cell culture Article CHO cell line colorectal cancer cell line covalent bond critical micelle concentration dispersity drug conjugation drug delivery system drug solubility drug targeting fluorescence microscopy HT-29 cell line human human cell human cell culture IC50 in vitro study MTT assay nonhuman stoichiometry therapeutic index animal chemistry colorectal tumor Cricetulus drug release metabolism micelle pathology transport at the cellular level AC133 Antigen Animals Biological Transport Carboxymethylcellulose Sodium CHO Cells Colorectal Neoplasms Drug Carriers Drug Liberation HT29 Cells Humans Micelles Polyethylene Glycols
Subjects: WI Digestive System
QV pharmacology
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 09 Jun 2020 05:25
Last Modified: 09 Jun 2020 05:25
URI: http://eprints.mums.ac.ir/id/eprint/17181

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