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:

Sreekanth V, Kar A, Kumar S, Pal S, Yadav P, Sharma Y, Komalla V, Sharma H, Shyam R, Sharma R.D, Mukhopadhyay A, Sengupta S, Dasgupta U, and Bajaj A. Bile Acid-tethered Docetaxel-based Nanomicelle Mitigates Tumor progression through Epigenetic Changes. Angew. Chem. Int. Ed. 2021, 60, 5394-5399.
Pal S, Medatwal N, Kumar S, Kar A, Komalla V, Yavvari P.S., Mishra D, Rizvi Z.R., Nandan S, Malakar D, Pillai M, Awasthi A, Das P, Sharma R. D., Srivastava A, Sengupta S, Dasgupta U, and Bajaj A. "A Localized Chimeric Hydrogel Therapy Combats Tumor Progression through Alteration of Sphingolipid Metabolism." ACS Central Sci. 2019, 5, 1648-1662.

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:

Pani T, Rajput K, Kar A, Sharma H, Basak R, Medatwal N, Saha S, Dev G, Kumar S, Gupta S, Mukhopadhyay A, Malakar D, Maiti TK, Aneeshkumar AG, Deo SVS, Sharma RD, Bajaj A, & Dasgupta U. Alternative Splicing of Ceramide Synthase 2 Alters Levels of Specific Ceramides and Modulates Cancer Cell Proliferation and Migration in Luminal B Breast Cancer Subtype. Cell Death Dis. 2021, 12, 171.
Medatwal N, Ansari M.N, Kumar S, Pal S, Jha S.K, Verma P, Rana K, Dasgupta U and Baja A. Hydrogel-mediated delivery of celastrol and doxorubicin induces a synergistic effect on tumor regression via upregulation of ceramides. Nanoscale 2020, 12, 18463-18475.

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:

Kumar S, Pal S, Thakur J, Rani P, Rana K, Kar A, Kar R, Mehta D, Jha S K, Jain D, Rajput K, Srivastava A, Dasgupta U, Patil V S, and Bajaj A. Non-immunogenic Hydrogel-mediated Delivery of Antibiotics Outperforms Clinically used Formulation in Mitigating the Wound Infections. ACS App. Mater. Inter. 2021, 13, 44041–44053.
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

​