title: A pH-responsive folate conjugated magnetic nanoparticle for targeted chemo-thermal therapy and MRI diagnosis.
abstract: Polyacrylic acid functionalized Fe3O4 nanoparticles (PAA-MNPs) of average size of 10 nm are prepared by a simple soft chemical approach. These PAA-MNPs are conjugated with folic acid through peptide bonding between the carboxylic group on the surface of PAA-MNPs and the amine group of folic acid. The good colloidal stability of FA conjugated MNPs makes it a promising candidate for targeted drug delivery, hyperthermia and as a MRI contrast agent with a transverse relaxivity R2 value of 105 mM(-1) s(-1). Folic acid conjugated magnetic nanoparticles (FA-MNPs) achieved ∼ 95% loading efficiency of doxorubicin (DOX) which could be due to strong electrostatic interaction of highly negatively charged FA-MNPs and the positively charged DOX. The drug release study shows a pH-dependent behavior and is higher in acidic pH (4.3 and 5.6) as compared to the physiological pH (7.3). Flow cytometry and confocal microscopic image analysis reveal that around 75-80% of HeLa cells undergo apoptosis due to DNA disintegration upon incubation with DOX-MNPs for 24 h. DOX-MNPs exhibit the synergistic effect due to the combination of DOX induced apoptosis and magnetic hyperthermia treatment (MHT) which enhance the cell death ∼ 95.0%. Thus, this system may serve as a potential pH sensitive nanocarrier for synergistic chemo-thermal therapy as well as a possible MRI contrast agent.
authors.affiliation: Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology Bombay, Mumbai 400076, India. dhirenb@iitb.ac.in.
authors.forename: Jagriti
authors.initials: J
authors.lastname: Gupta
authors.forename: Jeotikanta
authors.initials: J
authors.lastname: Mohapatra
authors.forename: Parag
authors.initials: P
authors.lastname: Bhargava
authors.forename: D
authors.initials: D
authors.lastname: Bahadur
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000000981:diagnostic imaging; D011859:Radiography; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
chemical_list: D000903:Antibiotics, Antineoplastic; D003287:Contrast Media; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D004317:Doxorubicin; D005492:Folic Acid