title: Hyaluronic acid-functionalized polymeric nanoparticles for colon cancer-targeted combination chemotherapy.
abstract: Nanoparticle (NP)-based combination chemotherapy has been proposed as an effective strategy for achieving synergistic effects and targeted drug delivery for colon cancer therapy. Here, we fabricated a series of hyaluronic acid (HA)-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs (HA-CPT/CUR-NPs) with various weight ratios of CPT to CUR (1 : 1, 2 : 1 and 4 : 1). The resultant spherical HA-CPT/CUR-NPs had a desirable particle size (around 289 nm), relative narrow size distribution, and slightly negative zeta potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the time frame examined. Subsequent cellular uptake experiments demonstrated that the introduction of HA to the NP surface endowed NPs with colon cancer-targeting capability and markedly increased cellular uptake efficiency compared with chitosan-coated NPs. Importantly, the combined delivery of CPT and CUR in one HA-functionalized NP exerted strong synergistic effects. HA-CPT/CUR-NP (1 : 1) showed the highest antitumor activity among the three HA-CPT/CUR-NPs, resulting in an extremely low combination index. Collectively, our findings indicate that this HA-CPT/CUR-NP can be exploited as an efficient formulation for colon cancer-targeted combination chemotherapy.
authors.affiliation: Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing, 400715, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.forename: Moon Kwon
authors.initials: MK
authors.lastname: Han
authors.forename: Emilie
authors.initials: E
authors.lastname: Viennois
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Si
authors.forename: Didier
authors.initials: D
authors.lastname: Merlin
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002166:Camptothecin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004357:Drug Synergism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008558:Melphalan / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D007074:Immunoglobulin G; D011108:Polymers; C051713:antineoplastic agent K 18; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid; D003474:Curcumin; D008558:Melphalan; D002166:Camptothecin