A localized hydrogel-mediated chemotherapy causes immunogenic cell death via activation of ceramide-mediated unfolded protein response

Kar, Animesh ; Jain, Dolly ; Kumar, Sandeep ; Rajput, Kajal ; Pal, Sanjay ; Rana, Kajal ; Kar, Raunak ; Jha, Somesh K. ; Medatwal, Nihal ; Yavvari, Prabhu Srinivas ; Pandey, Nishant ; Mehta, Devashish ; Sharma, Harsh ; Bhattacharya, Debanjan ; Pradhan, Manas K. ; Sharma, Ravi Datta ; Srivastava, Aasheesh ; Agrawal, Usha ; Mukhopadhyay, Arnab ; Sengupta, Sagar ; Patil, Veena S. ; Bajaj, Avinash ; Dasgupta, Ujjaini (2023) A localized hydrogel-mediated chemotherapy causes immunogenic cell death via activation of ceramide-mediated unfolded protein response Science Advances, 9 (26). ISSN 2375-2548

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Official URL: http://doi.org/10.1126/sciadv.adf2746

Related URL: http://dx.doi.org/10.1126/sciadv.adf2746

Abstract

Treatment of triple-negative breast cancer (TNBC) is challenging because of its “COLD” tumor immunosuppressive microenvironment (TIME). Here, we present a hydrogel-mediated localized delivery of a combination of docetaxel (DTX) and carboplatin (CPT) (called DTX-CPT-Gel therapy) that ensured enhanced anticancer effect and tumor regression on multiple murine syngeneic and xenograft tumor models. DTX-CPT-Gel therapy modulated the TIME by an increase of antitumorigenic M1 macrophages, attenuation of myeloid-derived suppressor cells, and increase of granzyme B+CD8+ T cells. DTX-CPT-Gel therapy elevated ceramide levels in tumor tissues that activated the protein kinase R (PKR)–like endoplasmic reticulum kinase (PERK)–mediated unfolded protein response (UPR). This UPR-mediated activation of apoptotic cell death led to release of damage-associated molecular patterns, thereby activating the immunogenic cell death that could even clear the metastatic tumors. This study provides a promising hydrogel-mediated platform for DTX-CPT therapy that induces tumor regression and effective immune modulation and, therefore, can be explored further for treatment of TNBC.

Item Type:Article
Source:Copyright of this article belongs to American Association for the Advancement of Science.
ID Code:136534
Deposited On:24 Jun 2025 09:41
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