Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles.
The incorporation of a high percentage of targeting molecules into drug delivery system is one of the important methods for improving efficacy of targeting therapeutic drugs to cancer cells. PLGA-based drug delivery carriers with folic acid (FA) as targeting molecule have a low targeting efficiency due to a low FA conjugation ratio. In this work, we fabricated a FA-conjugated PLGA system using a crosslinker 1, 3-diaminopropane and have achieved a high conjugation ratio of 46.7% (mol/mol). The as-prepared PLGA-based biomaterial was used to encapsulate therapeutic drug 5-fluorouracil (5-FU) into nanoparticles. In the in vitro experiments, an IC₅₀ of 5.69 µg/mL has been achieved for 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles on HT-29 cancer cells and is significantly lower than that of 5-FU and 5-FU loaded PLGA nanoparticles which only have an IC₅₀ of 22.9 and 14.17 µg/mL, respectively. The fluorescent microscopy images showed that nanoparticles with FA are largely taken up by HT-29 cancer cells and the targeting nanoparticles have more affinity to cancer cells than the pure drugs and untreated nanoparticles. Therefore, the 1, 3-diaminopropane can facilitate the conjugation of FA to PLGA to form a novel polymer and 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles can be a highly efficient system for specific delivery of drugs to cancer cells.
Institute for Frontier Materials, Deakin University , Waurn Ponds, VIC , Australia .
Yichao
Y
Wang
Puwang
P
Li
Lijue
L
Chen
Weimin
W
Gao
Fanbo
F
Zeng
Ling Xue
LX
Kong
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003432:Cross-Linking Reagents / Q000737:chemistry; D003959:Diamines / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties
D000964:Antimetabolites, Antineoplastic; D003432:Cross-Linking Reagents; D003959:Diamines; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005492:Folic Acid; C009475:trimethylenediamine; D005472:Fluorouracil
HT-29; PLGA-1, 3-diaminopropane-folic acid; nanoparticles; targeting