Page 54 - _NIPER-G Annual Report 2019-201

Research Area-4

Photo-Electro Active Nanocomposite Silk Hydrogel for Spatiotemporal Controlled
Release of Chemotherapeutics: An in Vivo Approach Towards Suppressing Solid
Tumor Growth. (Collaboration with IIT Guwahati)
Conventional systemic chemotherapeutic regimens suffer from challenges such as non-
specificity, shorter half-life, clearance of drugs and dose-limiting toxicity. Localized delivery of
chemotherapeutic drugs through noninvasive spatiotemporally controllable stimuli-responsive
drug delivery systems could overcome these drawbacks while utilizing drugs approved for
cancer treatment. In this regard, we developed photo-electro active nanocomposite silk-based
drug delivery systems (DDS) exhibiting, on-demand drug release in vivo. A functionally
modified single-walled carbon nanotube loaded with doxorubicin was embedded within cross-
linker free silk hydrogel. The resultant nanocomposite silk hydrogel showed electrical field
responsiveness and near-infrared (NIR) laser-induced hyper thermal effect. The remote
application of these stimuli in tandem or independent manner led to the increased thermal and
electrical conductivity of nanocomposite hydrogel, which effectively triggered the intermittent
on-demand drug release. In a proof-of-concept in vivo tumor regression study, the
nanocomposite hydrogel was administered in a minimally invasive way at the periphery of the
tumor by covering most of it. During the 21- day study, drastic tumor regression was recorded
upon regular stimulation of nanocomposite hydrogel with simultaneous or individual external
application of an electric field and NIR laser. Tumor cell death marker expression analysis
uncovered the induction of apoptosis in tumor cells leading to its shrinkage. Heart ultrasound
and histology revealed no cardiotoxicity associated with localized DOX treatment. To our
knowledge, this is also the first report to show the simultaneous application of electric field and
NIR laser in vivo for localized tumor therapy, and our results suggested that such strategy
might have high clinical translational potential.

Gangrade A, Gawali B, Jadi PK, Naidu VG, Mandal BB. Photo-Electro Active Nanocomposite
Silk Hydrogel for Spatiotemporal Controlled Release of Chemotherapeutics: An In Vivo
Approach Towards Suppressing Solid Tumor Growth. ACS Applied Materials & Interfaces.
2020 May 29.

Graphical Abstract

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