title: Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles for targeting anticancer delivery: Characterization and cellular cytotoxicity.
abstract: The aim of this work was to synthesize molecularly imprinted polymer-poly ethylene glycol-folic acid (MIP-PEG-FA) nanoparticles for use as a controlled release carrier for targeting delivery of paclitaxel (PTX) to cancer cells. MIP nanoparticles were synthesized by a mini-emulsion polymerization technique and then PEG-FA was conjugated to the surface of nanoparticles. Nanoparticles showed high drug loading and encapsulation efficiency, 15.6 ± 0.8 and 100%, respectively. The imprinting efficiency of MIPs was evaluated by binding experiments in human serum. Good selective binding and recognition were found in MIP nanoparticles. In vitro drug release studies showed that MIP-PEG-FA have a controlled release of PTX, because of the presence of imprinted sites in the polymeric structure, which makes it is suitable for sustained drug delivery. The drug release from polymeric nanoparticles was indeed higher at acidic pH. The molecular structure of MIP-PEG-FA was confirmed by Hydrogen-Nuclear Magnetic Resonance (H NMR), Fourier Transform InfraRed (FT-IR), and Attenuated Total Reflection (ATR) spectroscopy, and their thermal behaviors by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Scanning Electron Microscopy (SEM) and Photon Correlation Spectroscopy (PCS) results showed that nanoparticles have a smooth surface and spherical shape with an average size of 181 nm. MIP-PEG-FA nanoparticles showed a greater amount of intracellular uptake in folate receptor-positive cancer cells (MDA-MB-231 cells) in comparison with the non-folate nanoparticles and free PTX, with half maximal inhibitory concentrations (IC50) of 4.9 ± 0.9, 7.4 ± 0.5 and 32.8 ± 3.8 nM, respectively. These results suggest that MIP-PEG-FA nanoparticles could be a potentially useful drug carrier for targeting drug delivery to cancer cells.
authors.affiliation: Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran, Iran; Department of Chemistry, Amirkabir University of Technology, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Esfandyari-Manesh
authors.affiliation: Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Behrad
authors.initials: B
authors.lastname: Darvishi
authors.affiliation: Department of Chemistry, Amirkabir University of Technology, Tehran, Iran.
authors.forename: Fatemeh Azizi
authors.initials: FA
authors.lastname: Ishkuh
authors.affiliation: Department of Chemical Engineering, Sharif University of Technology, Tehran, Iran.
authors.forename: Elnaz
authors.initials: E
authors.lastname: Shahmoradi
authors.affiliation: Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran, Iran; Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Mohammadi
authors.affiliation: Department of Chemistry, Amirkabir University of Technology, Tehran, Iran.
authors.forename: Mehran
authors.initials: M
authors.lastname: Javanbakht
authors.affiliation: Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
authors.affiliation: Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran, Iran. Electronic address: atyabifa@tums.ac.ir.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000633:toxicity; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008855:Microscopy, Electron, Scanning; D054802:Molecular Imprinting; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; C552831:poly(ethylene glycol)-folate; D011092:Polyethylene Glycols; D005492:Folic Acid; D017239:Paclitaxel
keywords: Cell culture; Folate; Molecularly imprinted polymer; Nanoparticles; Paclitaxel; Targeting delivery