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: Bo Xiao, Mingzhen Zhang, Emilie Viennois, Yuchen Zhang, Na Wei, Mark T Baker, Yunjin Jung, Didier Merlin
• Journal: Biomaterials (Biomaterials) Vol. 48 Pg. 147-60 (Apr 2015) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 25701040 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Published by Elsevier Ltd.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Animals
• Colonic Neoplasms (drug therapy, genetics)
• Gene Expression
• In Vitro Techniques
• Mice
• Nanoparticles
• Surface Properties