title: Magnetic norbornene polymer as multiresponsive nanocarrier for site specific cancer therapy.
abstract: A site-specific, stimuli-responsive nanocarrier has been synthesized by conjugating folate, magnetic particles and doxorubicin to the backbone of norbornene polymer. Monomers, namely, cis-5-norbornene-6-(diethoxyphosphoryl)hexanote (mono 1), norbornene grafted poly(ethyleneglycol)-folate (mono 2), and norbornene derived doxorubicin (mono 3) are carefully designed to demonstrate the smart nanorcarrier capabilities. The synthesis and complete characterization of all three monomers are elaborately discussed. Their copolymerization is done by controlled/living ring-opening metathesis polymerization (ROMP) to get the triblock copolymer PHOS-FOL-DOX. NMR spectroscopy and gel permeation chromatography confirm the formation of the triblock copolymer, while FT-IR spectroscopy, thermogravimetric analysis, along with transmission electron microscope confirm the anchoring of iron particle (Fe3O4) to the PHOS-FOL-DOX. Drug release profile shows the importance of having the hydrazone linker that helps to release the drug exactly at the mild acidic conditions resembling the pH of the cancerous cells. The newly designed nanocarrier shows greater internalization (about 8 times) due to magnetic field. Also, increased intracellular DOX release is observed due to the folate receptor. From these results, it is clear that PHOS-FOL-DOX has the potential to act as a smart nanoreservoir with the magnetic field guidance, folate receptor targeting, and finally pH stimulation.
authors.affiliation: Polymer Research Centre, Department of Chemical Sciences, ‡Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata , BCKV main campus, Mohanpur P.O., Mohanpur, West Bengal, India 741252.
authors.forename: Vijayakameswara
authors.initials: V
authors.lastname: Rao N
authors.forename: Mutyala Naidu
authors.initials: MN
authors.lastname: Ganivada
authors.forename: Santu
authors.initials: S
authors.lastname: Sarkar
authors.forename: Himadri
authors.initials: H
authors.lastname: Dinda
authors.forename: Koushik
authors.initials: K
authors.lastname: Chatterjee
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Dalui
authors.forename: Jayasri
authors.initials: J
authors.lastname: Das Sarma
authors.forename: Raja
authors.initials: R
authors.lastname: Shunmugam
mesh_terms: D001896:Boron Compounds / Q000737:chemistry*; D004337:Drug Carriers; D008280:Magnetics; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D011108:Polymers / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry
chemical_list: D001896:Boron Compounds; D004337:Drug Carriers; D011108:Polymers