PhD Thesis Colloquium: Ms. Madhavi Tripathi (28/05/24)
Thesis title:
Thermoresponsive CuS-based nanocomposites Mimicking Red Blood Cells for Combinatorial Therapy and Photoacoustic Imaging
Faculty advisor(s):
Prof. Ashok M Raichur
When?
28th May, 2024 (Tuesday), 03:00 PM (India Standard Time)
Where
KPA Auditorium, Department of Materials Engineering
Abstract:
Treating advanced non-small cell lung cancer (NSCLC) presents significant challenges, particularly with traditional chemotherapy and molecular-targeted therapies. These treatments often suffer from limitations such as non-specific targeting, affecting both healthy and cancerous cells, low bioavailability, and the development of resistance by cancer cells, which reduces their effectiveness. Nano-drug delivery systems are revolutionizing lung cancer treatment. However, a major challenge is that only a small fraction of administered nanoparticles reach the target tumor site, with delivery rates as low as 0.7%. Smaller nanoparticles penetrate tumors more effectively but are quickly cleared from the body and have reduced drug-loading capacities. Conversely, larger nanoparticles can carry more drugs but may struggle to penetrate deeply into tumors. Overcoming these issues requires a unique combination of strategies. Additionally, most nanoparticles are attacked by the immune system, necessitating methods to evade immune detection.
Addressing the limitations and gaps of current drug delivery methods, this study aims to design a multistage delivery system that mimics red blood cells (RBCs) for site-specific drug delivery. This system integrates a tyrosine kinase inhibitor with copper sulfide (CuS) nanoparticles encapsulated within a thermoresponsive nanogel to achieve photothermal therapy (PTT), targeted chemotherapy, and photoacoustic imaging (PAI). Initially, various strategies were employed to prepare a robust and multifunctional CuS nanoparticle characterized by small size, functionalization capability, and optimal photothermal efficiency. This process involved exploring various methods and materials, which were evaluated for their material properties, phototheranostic capabilities, and anticancer properties. Ultimately, a particle prepared using Mucin was finalized and further evaluated for its in vivo photoacoustic imaging capability.
Next, to facilitate the on-demand release of CuS and the drug, a NIPAM-based nanogel was designed to degrade at elevated temperatures, allowing for targeted drug release. The nanogel was engineered to release its components only in response to thermal stimuli, with a transition temperature above body temperature. Additionally, the potential of coating this loaded nanogel with an RBC membrane to mimic natural RBCs was investigated, thereby avoiding immune responses and opsonization.
The nanoparticles underwent extensive in vitro assays and spheroid studies. The developed system was ultimately tested on lung tumor-bearing mouse models to evaluate its effectiveness. The results demonstrated a significant impact of the multistage and multimodal system on tumor regression compared to individual components, with no observed toxicity upon application.