RRC ID 69361
Author Lale SV, R G A, Aravind A, Kumar DS, Koul V.
Title AS1411 aptamer and folic acid functionalized pH-responsive ATRP fabricated pPEGMA-PCL-pPEGMA polymeric nanoparticles for targeted drug delivery in cancer therapy.
Journal Biomacromolecules
Abstract Nonspecificity and cardiotoxicity are the primary limitations of current doxorubicin chemotherapy. To minimize side effects and to enhance bioavailability of doxorubicin to cancer cells, a dual-targeted pH-sensitive biocompatible polymeric nanosystem was designed and developed. An ATRP-based biodegradable triblock copolymer, poly(poly(ethylene glycol) methacrylate)-poly(caprolactone)-poly(poly(ethylene glycol) methacrylate) (pPEGMA-PCL-pPEGMA), conjugated with doxorubicin via an acid-labile hydrazone bond was synthesized and characterized. Dual targeting was achieved by attaching folic acid and the AS1411 aptamer through EDC-NHS coupling. Nanoparticles of the functionalized triblock copolymer were prepared using the nanoprecipitation method, resulting in an average particle size of ∼140 nm. The biocompatibility of the nanoparticles was evaluated using MTT cytotoxicity assays, blood compatibility studies, and protein adsorption studies. In vitro drug release studies showed a higher cumulative doxorubicin release at pH 5.0 (∼70%) compared to pH 7.4 (∼25%) owing to the presence of the acid-sensitive hydrazone linkage. Dual targeting with folate and the AS1411 aptamer increased the cancer-targeting efficiency of the nanoparticles, resulting in enhanced cellular uptake (10- and 100-fold increase in uptake compared to single-targeted NPs and non-targeted NPs, respectively) and a higher payload of doxorubicin in epithelial cancer cell lines (MCF-7 and PANC-1), with subsequent higher apoptosis, whereas a normal (noncancerous) cell line (L929) was spared from the adverse effects of doxorubicin. The results indicate that the dual-targeted pH-sensitive biocompatible polymeric nanosystem can act as a potential drug delivery vehicle against various epithelial cancers such as those of the breast, ovary, pancreas, lung, and others.
Volume 15(5)
Pages 1737-52
Published 2014-5-12
DOI 10.1021/bm5001263
PMID 24689987
MeSH Antineoplastic Agents / administration & dosage Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Apoptosis / drug effects Aptamers, Nucleotide Biocompatible Materials / administration & dosage Biocompatible Materials / chemistry Biocompatible Materials / pharmacology* Cell Line Cell Proliferation / drug effects Cell Survival / drug effects Dose-Response Relationship, Drug Doxorubicin / administration & dosage Doxorubicin / chemistry Doxorubicin / pharmacology* Drug Delivery Systems* Drug Screening Assays, Antitumor Folic Acid / administration & dosage Folic Acid / chemistry Folic Acid / pharmacology* Humans Hydrogen-Ion Concentration MCF-7 Cells Molecular Structure Nanoparticles / administration & dosage Nanoparticles / chemistry* Oligodeoxyribonucleotides / administration & dosage Oligodeoxyribonucleotides / chemistry Oligodeoxyribonucleotides / pharmacology* Particle Size Polymerization Structure-Activity Relationship Surface Properties
IF 6.092
Human and Animal Cells MCF7(RCB1904) PANC-1(RCB2095) L929