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NIR-responsive Indocyanine green-Genistein Nanoformulation controlling Polycomb epigenetic machinery for efficient Photo-Chemo-Combotherapy of Glioblastoma

Abstract

Combinatorial photodynamic and chemotherapy have drawn enormous attention as therapeutic modalities via precise stimuli-responsive drug delivery in glioblatoma overcoming the limitations associated with conventional therapies. Herein we have prepared Indocyanine Green tagged, Genistein encapsulated Casein nanoformulation (ICG-Gen@CasNPs) exibiting Near Infra-Red region responsive controlled release of the Genistein and enhanced cellular uptake in human Glioblastoma monolayer and three-dimensional raft culture model via enhanced retention effect. ICG-Gen@CasNPs with integrated photosensitizer Indocyanin Green within nanoformulation triggering oxidative stress, activating apoptosis cascade, promoting cell cyce arrest and damaging mitochondrial membrane potenital collectively directed the Glioblastoma cell death. The suppression of polycomb group of proteins in Glioblastoma on ICG-Gen@CasNPs/NIR exposure realized the involvement of epigentic repression complex machinery in the regulation. Furthermore, the ICG-Gen@CasNPs/PDT/PTT directed ubiquitinaton and proteasomal degradation of EZH2 and BMI1 indicate the implication of Polycomb in confering glioblastoma survival. The increased activation of apoptotic pahways and cellular Reactive oxygen species generation on inhibiting expression level of EZH2 and BMI1 strengthen our observations. Of note, ICG-Gen@CasNPs robustly accumulated in the brain after crossing the blood brain barrier represented eminent biocompatibility and nonspecific toxicity in-vivo. Thus, this combinatorial chemo/photodynamic therapy revealed that ICG-Gen@CasNPs mediated epigenetic regulation –as a crucial molecular mechanism of GBM suppression.

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Publication details

The article was accepted on 13 Apr 2019 and first published on 16 Apr 2019


Article type: Paper
DOI: 10.1039/C9NA00212J
Citation: Nanoscale Adv., 2019, Accepted Manuscript
  • Open access: Creative Commons BY license
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    NIR-responsive Indocyanine green-Genistein Nanoformulation controlling Polycomb epigenetic machinery for efficient Photo-Chemo-Combotherapy of Glioblastoma

    B. Kaundal, A. K. SRIVASTAVA, M. N. Sardoiwala, S. Karmakar and S. Roy Choudhury, Nanoscale Adv., 2019, Accepted Manuscript , DOI: 10.1039/C9NA00212J

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