title: Folate targeted polymeric 'green' nanotherapy for cancer.
abstract: The concept of 'green' chemotherapy by employing targeted nanoparticle mediated delivery to enhance the efficacy of phytomedicines is reported. Poly (lactide-co-glycolide) (PLGA) nanoparticles encapsulating a well known nutraceutical namely, grape seed extract (GSE)-'NanoGSE'-was prepared by a nanoprecipitation technique. The drug-loaded nanoparticles of size approximately 100 nm exhibited high colloidal stability at physiological pH. Molecular receptor targeting of this nanophytomedicine against folate receptor over-expressing cancers was demonstrated in vitro by conjugation with a potential cancer targeting ligand, folic acid (FA). Fluorescence microscopy and flow cytometry data showed highly specific cellular uptake of FA conjugated NanoGSE on folate receptor positive cancer cells. Studies were also conducted to investigate the efficiency of targeted (FA conjugated) versus non-targeted (non-FA conjugated) nanoformulations in causing cancer cell death. The IC(50) values were lowered by a factor of approximately 3 for FA-NanoGSE compared to the free drug, indicating substantially enhanced bioavailability to the tumor cells, sparing the normal ones. Receptor targeting of FA-NanoGSE resulted in a significant increase in apoptotic index, which was also quantified by flow cytometry and fluorescence microscopy. This in vitro study provides a basis for the use of nanoparticle mediated delivery of anticancer nutraceuticals to enhance bioavailability and effectively target cancer by a 'green' approach.
authors.affiliation: Amrita Center for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi-682 041, Kerala, India.
authors.forename: Sreeja
authors.initials: S
authors.lastname: Narayanan
authors.forename: N S
authors.initials: NS
authors.lastname: Binulal
authors.forename: Ullas
authors.initials: U
authors.lastname: Mony
authors.forename: Koyakutty
authors.initials: K
authors.lastname: Manzoor
authors.forename: Shantikumar
authors.initials: S
authors.lastname: Nair
authors.forename: Deepthy
authors.initials: D
authors.lastname: Menon
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D005434:Flow Cytometry; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry / Q000494:pharmacology*; D056604:Grape Seed Extract / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000628:therapy*; D010316:Particle Size; D008517:Phytotherapy / Q000379:methods*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D044945:Proanthocyanidins / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D056604:Grape Seed Extract; D044945:Proanthocyanidins; D011956:Receptors, Cell Surface; C013221:proanthocyanidin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005492:Folic Acid