Introduction: Theranostics is an emerging area in nanomedicine which combines both therapy and diagnostics in a single domain. Polymer based theranostic agents are of particular interest as they are characterized by great diversity in terms of diagnostic and imaging modalities. The current strategy of constructing a polymer-based theranostic agent relies on the incorporation of fluorophores and magnetic resonance imaging contrast agents which have inherent drawbacks such as toxicity, high cost, low sensitivity and non-biodegradability[1]. Hence development of low cost and biocompatible PEG based self fluorescent polymeric theranostic systems is of great importance in biomedical research.
Methods: A fluorescent PEGylated comacromer was synthesized by polycondensation of PEG with maleic acid and glycine. The structure and photoluminescence of the PEGylated comacromer were analysed using proton NMR and fluorescence spectroscopy respectively.The Synthesized comacromer was then crosslinked with methacrylic acid to from nanogel. 5-Fluorouracil, a model colon cancer drug, was loaded inside the nanogel and studied the drug release. The colon cancer imaging capability of this nanogel was evaluated with HCT cell line.
Results and Discussion: The PEGylated comacromer is comprised of the units of maleic acid, PEG and glycine as revealed by the proton NMR spectra (Figure 1 a) with peaks at 6.8 ppm (CH=CH of maleic acid), 3.6 ppm (-CH2 groups of PEG) and 3.4 ppm (-CH2NH from glycine). The studies on fluorescence characteristics of the PEGylated comacromer reveal excitation dependent fluorescence characteristics (Fig 1b)
Figure 1: proton NMR spectra of PEGylated comacromer (a), Fluorescent spectra of PEGylated comacromer (b)
The size of synthesized nanogels was around 100 nm (Fig 2a). The studies on drug release of nanogel reveal pH sensitive drug release profile (Fig2b). The nanogel can cross the acidic pH of intestine and deliver more amount of drug in the colon having slightly alkaline pH. The observed higher drug release in alkaline pH is attributed to the ionizable –COOH groups of methacrylic acid which causes swelling in basic pH[2]. The studies on colon cancer imaging capability of this nanogel exhibit multiple emissions from colon cancer cell line (Fig 2c).
Figure 2: Transmission electron microscopy images of nanogels (a),pH sensitive drug release profile of 5-fluorouracil from nanogels (b), Colon cancer cell line (HCT) fluorescent imaging using nanogels (c)
Conclusion: The present nanogel of PEGylated comacromer displayed favorable therapeutic and diagnostic (theranostic) capabilities for colon cancer. To best of our knowledge this is the first report of a PEG based self fluorescent nanogel for colon cancer theranostic applications.
References:
[1] Xie, J.;Lee, S.;Chen, X.Adv. Drug Deliv. Rev.2010,62,1064–1079
[2] Kumar,N.;Asok,N.;Nair,S.;kumar,G,Int J Nanomedicine.2012,7,5769-5779