title: Inhibition of MDR1 gene expression and enhancing cellular uptake for effective colon cancer treatment using dual-surface-functionalized nanoparticles.
abstract: Nanomedicine options for colon cancer therapy have been limited by the lack of suitable carriers capable of delivering sufficient drug into tumors to cause lethal toxicity. To circumvent this limitation, we fabricated a camptothecin (CPT)-loaded poly(lactic-co-glycolic acid) nanoparticle (NP) with dual-surface functionalization-Pluronic F127 and chitosan-for inhibiting multi-drug resistant gene 1 (MDR1) expression and enhancing tumor uptake. The resultant spherical NPs-P/C had a desirable particle size (∼268 nm), slightly positive zeta-potential, and the ability to efficiently down-regulate the expression of MDR1. In vitro cytotoxicity tests revealed that the 24 and 48 h IC50 values of NPs-P/C1 were 2.03 and 0.67 μm, respectively, which were much lower than those for free CPT and other NPs. Interestingly, NPs-P/C1 showed the highest cellular uptake efficiency (approximately 85.5%) among the different drug formulations. Most importantly, treatment of colon tumor-bearing mice with various drug formulations confirmed that the introduction of Pluronic F127 and chitosan to the NP surface significantly enhanced the therapeutic efficacy of CPT, induced tumor cell apoptosis, and reduced systemic toxicity. Collectively, these findings suggest that our one-step-fabricated, dual-surface-functionalized NPs may hold promise as a readily scalable and effective drug carrier with clinical potential in colon cancer therapy.
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing 400715, PR China; Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA. Electronic address: bxiao@gsu.edu.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA.
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA; Atlanta Veterans Affairs Medical Center, Decatur, 30033, USA.
authors.forename: Emilie
authors.initials: E
authors.lastname: Viennois
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, 30302, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Baker
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA.
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA; Atlanta Veterans Affairs Medical Center, Decatur, 30033, USA.
authors.forename: Didier
authors.initials: D
authors.lastname: Merlin
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D015870:Gene Expression; D066298:In Vitro Techniques; D051379:Mice; D053758:Nanoparticles; D013499:Surface Properties
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1
keywords: Chemotherapy; Colon cancer; Enhanced cellular uptake; Multidrug resistant gene 1; Nanoparticles; Surface functionalization