Dual stimuli-responsive biotinylated polymer-drug conjugate for dual drug delivery.
Desoshree Ghosh, Afruja Khan, Sagar Bag, Amirul Islam Mallick, Priyadarsi De
Author Information
Desoshree Ghosh: Polymer Research Centre and Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur - 741246, Nadia, West Bengal, India. p_de@iiserkol.ac.in. ORCID
Afruja Khan: Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur - 741246, Nadia, West Bengal, India. amallick@iiserkol.ac.in. ORCID
Sagar Bag: Polymer Research Centre and Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur - 741246, Nadia, West Bengal, India. p_de@iiserkol.ac.in. ORCID
Amirul Islam Mallick: Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur - 741246, Nadia, West Bengal, India. amallick@iiserkol.ac.in. ORCID
Priyadarsi De: Polymer Research Centre and Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur - 741246, Nadia, West Bengal, India. p_de@iiserkol.ac.in. ORCID
Stimuli-responsive nanoscale polymer-drug conjugates are one of the most promising alternatives in the realm of advanced therapeutics, rendering several characteristics such as spatio-temporal control over drug release, reduced off-target toxicity, enhanced bioavailability, and longer blood circulation time of the drug. Fostered by the aforementioned conceptualization, our quest to develop an ideal polymer-drug conjugate has originated the present investigation of developing a reactive oxygen species (ROS) and esterase-responsive self-assembled polymer-drug (chlorambucil, CBL) conjugate with biotin pendants (DP2) for cancer cell targeting, surrogating another antineoplastic drug, doxorubicin (DOX) physical encapsulation (DP2@DOX). The ROS and esterase trigger not only released the covalently stitched CBL but also resulted in DOX release by dismantling the amphiphilic balance of the nanoaggregates. Biotinylation-mediated enhancement of cellular uptake of DP2@DOX was reflected in the synergistic anticancer activity of both the drugs (CBL and DOX) in HeLa cells (biotin receptor-positive cells) compared to HEK 293T cells (biotin receptor-negative cells). Furthermore, the selective internalization of the fluorophore-tagged DOX-loaded polymer (DP4@DOX) in HeLa cells compared to HEK 293T cells was confirmed by confocal microscopy and flow cytometry. In summary, the present investigation demonstrates a state-of-the-art self-assembled polymer-drug conjugate as a next-generation dual stimuli-responsive drug delivery vehicle.
