Tumor microenvironment responsive nanogels as a smart triggered release platform for enhanced intracellular delivery of doxorubicin

Kumar, Parveen and Behl, Gautam and Kaur, Sumeet and Yadav, Nalini and Liu, Bo and Chhikara, Aruna (2021) Tumor microenvironment responsive nanogels as a smart triggered release platform for enhanced intracellular delivery of doxorubicin. Journal of Biomaterials Science, Polymer Edition, 32 (3). pp. 385-404. ISSN 0920-5063

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Abstract

The fabrication of novel and intelligent delivery systems that can effectively deliver therapeutics to the targeted site and release payload in enhanced/controlled manner is highly desired to overcome the multiple challenges in chemotherapy. The present article demonstrates the potential application of dual stimuli responsive nanogels as tumor microenvironment targeted drug delivery carrier. Disulfide cross-linked pH and redox responsive PEG-PDMAEMA nanogels were synthesized by atom transfer radical polymerization (ATRP). The nanogels were characterized by nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The PEG-PDMAEMA nanogels exhibited dual stimuli-responsive release of the encapsulated model anticancer drug (doxorubicin, DOX) due to the acidic pH-response of dimethyl amine group in PDMAEMA and reductive cleavage of the disulfide linkages. A relatively higher release of DOX was observed from the nanogels at pH 5.0 than at pH 7.4. DOX release was further accelerated in tumor simulated environment of pH 5.0 and 10 mM glutathione (GSH). Confocal microscopy images revealed that DOX-loaded PEG-PDMAEMA nanogels can rapidly internalize and effectively deliver the drug into the cells. The nanogels exhibited higher cytotoxicity in GSH-OEt pretreated HeLa cells than untreated cells. The dual stimuli responsive nanogels synthesized in this study exhibited many favorable traits, such as pH and redox dependent controlled release of drug, biodegradability, biocompatibility, and enhanced cytotoxicity, which endow them as a promising candidate for anticancer drug delivery.

Item Type:	Article
Additional Information:	Funding Information: Financial supports from the Department of Biotechnology, India (grant number P87/RGCB/PMD/DBT/ARCH/2015) are greatly acknowledged and Parveen Kumar acknowledges Department of Biotechnology, India (grant number P87/RGCB/PMD/DBT/ARCH/2015) for providing fellowship. The authors would also like to acknowledge Dr. Madhu Chopra (Assistant Professor), Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, India for her immense guidance and contribution to the project, and providing required facilities for its completion. Publisher Copyright: © 2020 Informa UK Limited, trading as Taylor & Francis Group.
Uncontrolled Keywords:	/dk/atira/pure/subjectarea/asjc/1300/1304
Departments or Groups:
Depositing User:	Admin SSL
Date Deposited:	19 Oct 2022 23:09
Last Modified:	13 Aug 2023 22:50
URI:	http://repository-testing.wit.ie/id/eprint/4364

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