title: Co-delivery of camptothecin and curcumin by cationic polymeric nanoparticles for synergistic colon cancer combination chemotherapy.
abstract: Nanoparticle (NP)-based combination chemotherapy has been proposed as a potent strategy for enhancing intracellular drug concentrations and achieving synergistic effects in colon cancer therapy. Here, we fabricated a series of chitosan-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs with various weight ratios of CPT to CUR. The resultant cationic spherical CPT/CUR-NPs had a desirable particle size (193-224 nm), relatively narrow size distribution, and slightly positive zeta-potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the study period with a slight, initial burst release. Subsequent cellular uptake experiments demonstrated that the introduction of chitosan to the NP surface markedly increased cellular-uptake efficiency compared with other drug formulations, and thus increased the intracellular drug concentrations. Importantly, the combined delivery of CPT and CUR in a single NP enhanced synergistic effects of the two drugs. Among the five cationic CPT/CUR-NPs tested, NPs with a CPT/CUR weight ratio of 4:1 showed the highest anticancer activity, resulting in a combination index of approximately 0.46. In summary, our study represents the first report of combinational application of CPT and CUR with a one-step-fabricated co-delivery system for effective colon cancer combination chemotherapy.
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing, 400715, P. R. China ; Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Georgia State University, Atlanta, 30302, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing, 400715, P. R. China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Si
authors.affiliation: Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Georgia State University, Atlanta, 30302, USA.
authors.forename: Moon Kwon
authors.initials: MK
authors.lastname: Han
authors.affiliation: Center for Diagnostics and Therapeutics, Institute for Biomedical Science, 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: Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Georgia State University, Atlanta, 30302, USA.
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Georgia State University, Atlanta, 30302, USA. ; Atlanta Veterans Affairs Medical Center, Decatur, 30033, USA.
authors.forename: Didier
authors.initials: D
authors.lastname: Merlin