title: "Clickable", trifunctional magnetite nanoparticles and their chemoselective biofunctionalization.
abstract: A multifunctional iron oxide based nanoformulation for combined cancer-targeted therapy and multimodal imaging has been meticulously designed and synthesized using a chemoselective ligation approach. Novel superparamagnetic magnetite nanoparticles simultaneously functionalized with amine, carboxyl, and azide groups were fabricated through a sequence of stoichiometrically controllable partial succinylation and Cu (II) catalyzed diazo transfer on the reactive amine termini of 2-aminoethylphosphonate grafted magnetite nanoparticles (MNPs). Functional moieties associated with MNP surface were chemoselectively conjugated with rhodamine B isothiocyanate (RITC), propargyl folate (FA), and paclitaxel (PTX) via tandem nucleophic addition of amine to isothithiocyanates, Cu (I) catalyzed azide--alkyne click chemistry and carbodiimide-promoted esterification. An extensive in vitro study established that the bioactives chemoselectively appended to the magnetite core bequeathed multifunctionality to the nanoparticles without any loss of activity of the functional molecules. Multifunctional nanoparticles, developed in the course of the study, could selectively target and induce apoptosis to folate-receptor (FR) overexpressing cancer cells with enhanced efficacy as compared to the free drug. In addition, the dual optical and magnetic properties of the synthesized nanoparticles aided in the real-time tracking of their intracellular pathways also as apoptotic events through dual fluorescence and MR-based imaging.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721302, India. md_manasmita@yahoo.com
authors.forename: Manasmita
authors.initials: M
authors.lastname: Das
authors.forename: Debarati
authors.initials: D
authors.lastname: Bandyopadhyay
authors.forename: Debasish
authors.initials: D
authors.lastname: Mishra
authors.forename: Satyajit
authors.initials: S
authors.lastname: Datir
authors.forename: Prasanta
authors.initials: P
authors.lastname: Dhak
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
authors.forename: Tapas Kumar
authors.initials: TK
authors.lastname: Maiti
authors.forename: Amit
authors.initials: A
authors.lastname: Basak
authors.forename: Panchanan
authors.initials: P
authors.lastname: Pramanik
mesh_terms: D000588:Amines / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D001386:Azides / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D057930:Click Chemistry; D052203:Ferrosoferric Oxide / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005492:Folic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry; D010316:Particle Size; D012235:Rhodamines / Q000737:chemistry; D013499:Surface Properties; D013696:Temperature; D014018:Tissue Distribution
chemical_list: D000588:Amines; D001386:Azides; D012235:Rhodamines; D005492:Folic Acid; C027755:rhodamine isothiocyanate; D017239:Paclitaxel; D052203:Ferrosoferric Oxide