(4hr) Harnessing Nanotechnology, Microfluidics, and Molecular Biology Techniques to Synthesize Biohybrid Drug Delivery Systems

Research Interests

Research experience:

Advisor: Kytai Nguyen (University of Texas, Arlington TX)

During my doctoral work I developed nanocomposites that can enhance intracellular drug delivery targeting viral and bacterial lung diseases via coating of cell penetrating peptides onto polymer nanoparticles. A multidisciplinary approach combining biochemistry, drug delivery, and material sciences was employed to synthesize these novel nanocomposites. Apart from this, I lead several other projects involving the development of antibody conjugated targeted therapeutics for cardiovascular diseases (targeted delivery of nucleic acids to endothelium in zebrafish), cardiac hypertrophy (targeted inhibition of hypertrophic cardiomyocytes), and cancer (using targeted immunotherapy via nanoparticle drug delivery). Towards cancer, I was one of the leading authors on the technology of engineered CAR-T cell membrane coated NPs for targeted chemotherapy, which is also being commercialized through the spinout company where I am a co-founder and scientific advisor. I was involved in developing targeted drug delivery systems for various pathological disease models resulting in various publications and grants. (04/2018 – 05/2022)

Advisor: Jina Ko (University of Pennsylvania, Philadelphia, PA)

I joined Dr. Jina Ko's lab at the University of Pennsylvania to expand my expertise in material chemistry and nanotechnology and address the challenges associated with synthetic nanoparticles used in drug delivery. Transitioning from nanomaterials to micro/nano-fluidics, extracellular vesicles (EVs), and molecular biology, I embarked on postdoctoral research that led to biomimetics and drug delivery systems. I developed a droplet microfluidic platform capable of robust and high-throughput synthesis of hybrid nanoparticles. This platform integrated biological target-specific CAR exosomes for intrinsic targeting with nanomaterial lipid nanoparticles (LNPs) for drug delivery. Our research has demonstrated that combining biological EVs with synthetic LNPs enhances drug delivery efficacy and targeting specificity. Additionally, we are pioneering a bottom-up approach to synthesize smart vesicles using synthetic biology techniques. I have also successfully isolated plant EVs for potential use in cancer treatment, highlighting their effectiveness as drug delivery vesicles. (07/2022-06/2025). Overall, combining biological knowledge of extracellular vesicles and my experience in nanoparticle technology, I have developed a formulation platform for novel biomimetic EV hybrid drug delivery system, which can also be employed for diagnostics.

Research interests:

The circulation and communication of materials within the human body rely on several key components and signaling molecules. Synthetic nanoparticles, however, still face challenges such as rapid clearance and off-target effects. By utilizing the platform I developed, we can merge natural extracellular vesicles (EVs) from various sources, including plants and humans, with synthetic particles like lipid nanoparticles (LNPs) to effectively target and deliver diverse cargos (e.g., nucleic acids, proteins, small molecules, plasmid DNA) for disease treatment. Furthermore, our platform is being used to develop diagnostic probes for in-situ detection of biomarkers within EVs. Consequently, my research sits at the confluence of nanotechnology, microfluidics, and molecular biology, aiming to innovate in both therapeutic and diagnostic domains.

Teaching Interests:

I have gained significant teaching experience on topics including drug delivery, biomaterials, and biomedical engineering as a graduate teaching assistant and instructor for 3 years which involved supervision of labs and be an active part in design of syllabus. Additionally, I have mentored more than 20 students (undergraduate and graduates) in various projects. I look forward to teaching introductory as well as advances courses in these fields. My focus will be to teach students courses which will prepare them to work in nanotechnology, microfluidics, molecular engineering and drug delivery fields (e.g., Engineering targeted medicine, Microfluidics for biological application).

Selected Honors, Publications, & Patents:

Dr. Franklyn Alexandar Scholarship for academic excellence and outstanding student (2016, 2018 and 2022)

I-engage mentoring award for REU program at UTA (2019)

Guest Editor invitation for Frontiers, Bioengineering and Biotechnology journal

R21 research grant for cardiomyopathy research done in PhD

Patent application

NANOCOMPOSITES FOR ENHANCED CELLULAR PAYLOAD DELIVERY

U.S. Provisional Application No. 63/413,102

Filing Date: October 4, 2022

Yaman S, Chintapula U*, Rodriguez E, Ramachandramoorthy H, Nguyen KT. Cell-mediated and cell membrane-coated nanoparticles for drug delivery and cancer therapy. Cancer Drug Resist. 2020; 3:879-911

Messerschmidt VL, Chintapula U*, Kuriakose AE, Laboy S, Truong TTD, Kydd LA, Jaworski J, Pan Z, Sadek H, Nguyen KT and Lee J (2021) Notch Intracellular Domain Plasmid Delivery via Poly (Lactic-Co-Glycolic Acid) Nanoparticles to Upregulate Notch Pathway Molecules. Front. Cardiovas. Med., 2021

Chintapula U, Yang S, Nguyen T, Yang Liu, Dong H, Nguyen KT, Supermolecular Peptide Nanofiber/PLGA Nanocomposites for Enhancing Pulmonary Drug Delivery (Published DOI: 10.1021/acsami.2c15204 American Chemical Society – Applied Materials and interfaces (Journal Cover)

Yaman S, Ramachandramoorthy H, Sabnani M, Chintapula U , Nguyen T, Iyer, P, Kotadia, T, Pop L, Hannan R, Weidanz JA, Nguyen KT; Lung Cancer Targeted Chemotherapy via Herceptin Based Chimeric Antigen Receptor (CAR) Engineered T Cell Membrane Coated Synthetic Nanoparticles, Bioactive materials, https://doi.org/10.1016/j.bioactmat.2023.12.027

D.E. Reynolds, J. Lim, Y. Roh, U. Chintapula, RT. Morales, D. Oh, J. Ko. “Droplet and Digital Microfluidics: Ideation to Implementation.” (Published, Elsevier), https://doi.org/10.1016/B978-0-443-15416-4.00008-6

Chintapula U, Oh Danny, Cristina Perez, Sachin Davis, Stanger B, Ko Jina, Anti-cancer effects of Sweet Basil Plant derived EVs to treat pancreatic cancer, Journal of extracellular biology, 10.1002/jex2.142

Chintapula U, S Karim, Iyer P, Nepune B, Bai F, Nguyen KT, Nanocomposites loaded with RDV as a drug delivery system against COVID-19, RSC Nanoscale Advances (Journal Cover), https://doi.org/10.1039/D4NA00361F