Research

We are currently running three different research programs: developing next-generation nanomedicines for cancer immunochemotherapy, understanding the role of sphingolipid and ganglioside metabolism on therapeutic interventions, and developing next generation biomaterials for anti-inflammatory, antimicrobial, and gene therapy applications.

Cancer Immunochemotherapy

We are developing novel chimeric lipid nanoparticles for targeting the key components of tumor microenvironment including cancer and immune cells, and exploring the effect of these nanomedicines on immunogenic cell death. We demonstrated, for the first time, that bile acid phospholipid-drug conjugates are more effective in murine cancer models, and are more tolerable than clinically used formulations in non-human primates (Angew. Chem Int. Ed. 2021). We were the first to show that sustained delivery of combination of anti-proliferative, anti-angiogenesis, and anti-inflammatory drugs using hydrogel implant can mitigate the tumor progression (ACS Central Sci. 2019). We are currently studying the impact of cancer nanomedicines on tumor-promoting and tumor-inhibiting immune cells, and how combination of immune adjuvants and chemotherapy drugs in combination with immune checkpoint inhibitors can be used for cancer therapy.

Relevant Publications:

Yadav P, Rana K, Nardini V, Khan A, Pani T, Kar A, Jain D, Chakraborty R, Singh R, Jha SK, Mehta D, Sharma H, Sharma RD, Deo SVS, Sengupta S, Patil VS, Faccioli LH, Dasgupta U, Bajaj A*. Engineered Nanomicelles inhibit the tumour progression via abrogating the prostaglandin-mediated immunosuppression. J. Control. Release. 2024, 368, 548-565.
Sreekanth V, Kar A, Kumar S, Pal S, Yadav P, Sharma Y, Komalla V, Sharma H, Shyam R, Sharma R.D, Mukhopadhyay A0, Sengupta S, Dasgupta U, & Bajaj A. Bile Acid-tethered Docetaxel-based Nanomicelle Mitigates Tumor progression through Epigenetic Changes. Angew. Chem. Int. Ed. 2021, 60, 5394-5399

Sphingolipid Biology and Cancer therapy

We are studying the impact of different therapeutic interventions like dietary restriction and chemotherapy on sphingolipid and ganglioside metabolism. We for the first time showed that chemotherapeutic regimens cause global alternative splicing, and sphingolipid-metabolizing enzymes are one of the key targets of chemotherapy (ACS Central Sci 2019). We also showed that combination chemotherapy causes increase in ceramides through altering the expression of different sphingolipid-metabolizing enzymes (Nanoscale 2020, ACS Central Sci 2019). We are currently working on impact of elucidating the role of sphingolipid and ganglioside metabolism in activating the unfolded protein response and autophagy in response to different therapeutic interventions.

Relevant Publications:

Yadav P, Rana K, Chakraborty R, Khan A, Mehta D, Jain D, Aggarwal B, Jha S, Dasgupta U, Bajaj A, Engineered Nanomicelles Targeting the Proliferation and Angiogenesis Inhibit the Tumour Progression by Impairing the Synthesis of Ceramide-1-Phosphate. Nanoscale. 2024, 16, 10350-10365.
Kar A, Jain D, Kumar S, Rajput K, Pal S, Rana K, Kar R, Jha SK, Medatwal N, Yavvari PS, Mehta D, Pradhan MK, Pandey N, Srivastava A, Mukhopadhyay A, Agarwal U, Sengupta S, Patil VS, Bajaj A, and Dasgupta U. A Localized Hydrogel-mediated Chemotherapy Causes Immunogenic Cell Death via Activation of Ceramide-mediated Unfolded Protein Response. Sci. Adv. 2023, 9.

Advanced Therapeutics

We are developing biological inert (nonimmunogenic) biomaterials (implants, nanogels, lipid nanoparticles) that can be used for sustained delivery of antibiotics, steroids, and gene therapeutics. We for the first time showed that low molecular weight hydrogels can be used as implants for sustained delivery of combination of four anti-tuberculosis drugs to reduce the bacterial burden in mice tuberculosis model (Nanoscale 2021). We also showed that topical delivery of antibiotic-loaded hydrogel is more effective than clinically used antibiotic creams for clearing wound infections (ACS App. Mater. Inter. 2021). We were the first to use polymeric nanogels for oral delivery of gene therapeutics to target post-translation modifications (SUMOlyation) for mitigation of gut inflammation (Inflammatory bowel disease (IBD)) (Nanoscale 2019). Currently we are developing long-lasting hydrogel implants for inflammatory disorders like cirrhosis, psoriasis, and IBD, developing mimics of antimicrobial peptides for clearing the bacterial/fungal infections, and engineering lipid/polymer-nanoparticles for delivery of mRNA vaccines and genome-editing (CRISPR/Cas9) applications.

Relevant Publications:

Rana K, Pani T, Jha S K, Mehta D, Yadav P, Jain D, Pradhan M K, Mishra S, Kar R, G BR, Srivastava A, U Dasgupta U, Patil V S, and Bajaj A. Hydrogel-mediated Topical Delivery of Steroids can Effectively Alleviate Psoriasis via Attenuating the Autoimmune Responses. Nanoscale 2022, 14, 3834-3848
Pal S, Soni V, Kumar S, Jha SK, Medatwal N, Rana K, Yadav P, Mehta D, Jain D, Kar R, Srivastava A, V. Patil VS, Dasgupta U, Nandicoori V, and Bajaj A. A Hydrogel-based Implantable Multidrug Antitubercular Formulation Outperforms Oral Delivery. Nanoscale 2021, 13, 13225-13230.
Yavvari PS, Verma P, Mustfa S, Pal S, Kumar S, Awasthi AK, Ahuja V, Srikanth CV, Srivastava A, and Bajaj A. A Nanogel Based Oral Gene Delivery System Targeting SUMOylation Machinery to Combat Gut Inflammation. Nanoscale, 2019,11, 4970-4986.
Yadav K, Kumar S, Mishra S, Asad M, Mitra M, Yavvari PS, Gupta S, Vedantham M, Ranga P, Komalla V, Pal S, Sharma P, Kapil A, Singh A, Singh N, Srivastava A, Thukral L and Bajaj A. Deciphering the Role of Intramolecular Networking in Cholic Acid-Peptide Conjugates (CAPs) at Lipopolysaccharide Surface in Combating Gram-negative Bacterial Infections. J. Med. Chem. 2019, 62, 1875–1886.

Research

Cancer Immunochemotherapy

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