Orthogonal biofunctionalization of magnetic nanoparticles via ``clickable'' poly(ethylene glycol) silanes: a ``universal ligand'' strategy to design stealth and target-specific nanocarriers

Das, Manasmita and Bandyopadhyay, Debarati and Singh, Raman Preet and Harde, Harshad and Kumar, Sunil and Jain, Sanyog (2012) Orthogonal biofunctionalization of magnetic nanoparticles via ``clickable'' poly(ethylene glycol) silanes: a ``universal ligand'' strategy to design stealth and target-specific nanocarriers. In: JOURNAL OF MATERIALS CHEMISTRY, 22 (47). pp. 24652-24667.

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Abstract

The present work demonstrates a novel strategy to synthesize orthogonally bio-engineered magnetonanohybrids (MNPs) through the design of versatile, biocompatible linkers whose structure includes: (i) a robust anchor to bind with metal-oxide surfaces; (ii) tailored surface groups to act as spacers and (iii) a general method to implement orthogonal functionalizations of the substrate via ``click chemistry''. Ligands that possess the synthetic generality of features (i)-(iii) are categorized as ``universal ligands''. Herein, we report the synthesis of a novel, azido-terminated poly(ethylene glycol) (PEG) silane that can easily self-assemble on MNPs through hetero-condensation between surface hydroxyl groups and the silane end of the ligand, and simultaneously provide multiple clickable sites for high density, chemoselective bio-conjugation. To establish the universal-ligand-strategy, we clicked alkyl-functionalized folate onto the surface of PEGylated MNPs. By further integrating a near-infrared fluorescent (NIRF) marker (Alexa-Fluor 647) with MNPs, we demonstrated their folate-receptor mediated internalization inside cancer cells and subsequent translocation into lysosomes and mitochondria. Ex vivo NIRF imaging established that the azido-PEG-silane developed in course of the study can effectively reduce the sequestration of MNPs by macrophage organs (viz. liver and spleen). These folate-PEG-MNPs were not only stealth and noncytotoxic but their dual optical and magnetic properties aided in tracking their whereabouts through combined magnetic resonance and optical imaging. Together, these results provided a strong motivation for the future use of the ``universal ligand'' strategy towards development of ``smart'' nanohybrids for theragnostic applications.

Item Type:	Journal Article
Publication:	JOURNAL OF MATERIALS CHEMISTRY
Publisher:	ROYAL SOC CHEMISTRY
Additional Information:	Copyright for this article belongs to ROYAL SOC CHEMISTRY, ENGLAND
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	31 Dec 2012 08:22
Last Modified:	31 Dec 2012 08:22
URI:	http://eprints.iisc.ac.in/id/eprint/45608

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