Research Overview

Interdisciplinary research at the intersection of Chemistry, Nanotechnology, Biology, and Medicine

Here are the techniques we use in The Sharma Lab, The Sharma Lab

Cell-Targeted Drug Delivery for Brain Diseases

The ineffectiveness of drug delivery across the blood-brain barrier (BBB) has long been a significant obstacle in treating brain disorders. The BBB is a highly selective permeable barrier that protects the brain from harmful substances, but it also prevents most therapeutic agents from reaching the brain. Even if drugs or nanoparticles manage to cross the impaired BBB following brain injury or neuroinflammation, achieving sufficient uptake in key cells involved in brain diseases, such as neurons, remains a major challenge. Drug delivery to injured neurons is particularly difficult due to several factors. Neurons have a less phagocytic nature compared to glial cells. Neurons are more passive recipients of therapeutic agents, making efficient drug delivery to these cells more challenging. Moreover, neurons exist in various types, each performing specific functions in the brain. So, it is crucial to target the specific ones involved in a particular disease.

To address these challenges, we are designing novel nanomaterials with inherent targeting capabilities to target neurons and other diseased cells in the brain using minimally-invasive systemic administration. We develop these nanomaterials using highly efficient chemical transformations in a minimum number of reaction steps to reduce synthetic burden.

Dhull et al. Theranostics 2024 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155412/

Iqbal et al. Bioengineering & Translational Medicine 2025, https://aiche.onlinelibrary.wiley.com/doi/full/10.1002/btm2.70053

PSMA-targeted Nanotherapies for Prostate Cancer

Prostate cancer is the second leading cause of cancer-related deaths among men in the United States. While early-stage treatments are often successful, with promising 5-year survival rates, the prognosis for advanced prostate cancer remains poor. Localized disease can be treated with radical prostatectomy and/or radiotherapy, but approximately one-third of patients experience recurrence. Currently, the standard of care for advanced prostate cancer is androgen deprivation therapy. However, most patients only benefit from this for less than 24 months before developing castration-resistant disease. For those with metastatic castration-resistant prostate cancer, treatment options provide only limited survival benefits.

This research area seeks to develop novel therapeutic strategies to improve outcomes for patients with advanced prostate cancer, by exploring innovative and targeted nano-approaches that go beyond the limitations of current treatments.

Dhull et al. Nanoscale 2024 https://pubs.rsc.org/en/content/articlelanding/2024/nr/d3nr06520k

Rani et al. Biomacromolecules, 2024, https://pubs.acs.org/doi/10.1021/acs.biomac.4c00878

Convenient and Scalable Methodologies for Designing Clinically Translatable Nanomaterials

In recent years, nanotechnology has significantly advanced healthcare by providing sophisticated drug delivery systems. Among these nanosystems, dendrimers stand out as a promising class of hyperbranched and monodisperse polymers, offering exciting prospects for targeted drug delivery. Despite continuous progress in the field of dendrimers, their clinical utility has been limited mainly due to challenges associated with their chemistry. This necessitates further optimization of their design regarding defect-free structures, a high number of end groups at lower generations, precise numbers of different surface groups, batch-to-batch reproducibility, safety, cost, and commercialization. Dendrimer-mediated drug delivery often relies on the following key features: a high number of surface groups for the conjugation of optimal drug payload, high molecular weights for longer blood circulation, and precise numbers of different surface groups for the simultaneous attachment of multiple ligands such as drugs, targeting agents, or imaging dyes. Considering these criteria, this research area aims to develop convenient structural designs and facile chemical pathways to create biocompatible, water-soluble, scalable, hetero-functional, and clinically translatable dendrimer scaffolds for drug delivery and imaging applications.

Dhull et al. ACS Sensors, 2025, https://pubs.acs.org/doi/10.1021/acssensors.4c03544

Iqbal et al. ACS Applied Materials & Interfaces, 2025, https://pubs.acs.org/doi/10.1021/acsami.5c04744

Castaneda et al. WIRES Nanomedicine & Nanobiotechnology; 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11994986/

Pulukuri et al. Biomacromolecules; 2025,https://pubs.acs.org/doi/full/10.1021/acs.biomac.5c00917