Research

Research Direction #1. Developing Biomimetic Nanoengineering Strategies for Customizable Nanocarriers in Targeted Delivery

Conventional nanoparticle-based therapeutics require precise delivery to targeted sites for desired effects. However, these nanoparticles are often recognized by the immune system and cleared by Kupffer cells, hindering their clinical use. To address this, we and others have shown that coating nanocarriers with cell membranes from natural cells, like red blood cells, enables immune evasion, prolonged circulation, and targeted delivery to solid tumors. Building upon this, we will develop new strategies that will allow us to rationally design NPs having biomimetic characteristics including deep tumor penetration, enhanced pharmacokinetics, reduced protein corona formation. Leveraging these features will allow us to make disease-specific biomimetic NPs when interrogating tumor microenvironment before, during, and after interventional procedures.

Reference publications:
(1) Srivastava, I et al., ACS Nano 16 (5), 8051-8063. (2022) (Link); (2) Srivastava, I et al., Advanced Biology 2 (3), 1800009 (2018) (Link); (3) Schwartz-Duval, A. et al., Nat. Comm. 11, 4530 (2020) (Link); (4) Schwartz-Duval, A. et al., ACS Applied Mater. Interfaces 13 (39), 46464-46477 (2021) (Link); (5) Tripathi, I. et al., ACS Applied Mater. Interfaces 10 (44), 37886–37897 (2018) (Link)

Research Direction #2. Developing Nanoengineering Tools and Platforms for Image-Guided Surgical Interventions.

Nanotechnology revolutionizes image-guided surgery, ensuring precision and minimally invasive procedures. Nano-sized imaging agents show promise in enhancing visualization of pathological areas, yet many lack clinical validation from surgeons. To bridge this gap, we collaborate closely with surgeons to tailor imaging agents for cancer surgery, accounting for surgical nuances. For instance, real-time fluorescence imaging significantly enhances tumor resection outcomes, especially in heterogeneous tumors where detecting multiple overexpressed cancer biomarkers with precision is crucial. To overcome the challenge of multiple excitation wavelengths, we've developed biomimetic nanoparticles targeting folate and αυβ3 integrins, utilizing a single excitation wavelength for camera sensors. Our pre-clinical evaluation, spanning in vitro tumor cells, ex vivo tumor cell-mimicking models, and in vivo mouse xenografts, demonstrates improved biocompatibility, extended circulation, reduced liver uptake, specific fluorescence enhancement in tumors, and valuable insights into cancer progression. Currently, we are developing 3D tumor cell-mimicking phantoms models that mimics in vivo tumor complexity and optics, and use it for evaluating NIR-I and NIR-II imaging agents. 

Reference publications:
(1) Srivastava, I.* et al., ACS Nano 17 (9), 8465-8482 (2023) (Link); (2) Srivastava, I.*, Xue, R. et al., ACS Applied Materials & Interfaces (2024) (Link); (3) George, M. B. et al., Journal of Biomedical Optics, 28 (5), 056002 (2023) (Link); (4) Chen, C. et al., Science Advances, 9, eadk3860 (2023) (Link)

Research Direction #3. Rational Design & Development of Liquid Biopsy Platforms For Early Disease Diagnostics

Reference publications:
(1) Misra, S. K.,+ Srivastava, I.+ et. al., J. Am. Chem. Soc. 139 (5), 1746-1749 (2017)  (Link); (2) Srivastava, I.+ Sar, D.+ et al., Nanoscale 11, 8226-8236 (2019) (Link); (3)Pandit, S. et al., ACS Sensors 4 (10), 2730-2737 (2019) (Link); (4)Srivastava, I. et al., ACS Applied Mater. Interfaces 12 (14), 16137-16149  (2020) (Link); (5) Alafeef, M. et al., ACS Sensors 5 (6), 1689-1698 (2020) (Link); (6) Srivastava, I. et al., Small Methods 4, 2000099 (2020) (Link); (7)Srivastava, I. et al., ACS Applied Mater. Interfaces 13 (50), 59747-59760 (2021) (Link)

Potential Collaborations:  We are open to initiating collaboration within Texas Tech University, Texas Tech Health Sciences Center and beyond. Feel free to reach out to Dr. Srivastava at indrajit.srivastava [at] ttu [dot] edu directly for potential collaborations.

Ongoing Collaborations: 

(i) Dr. Klementina Fon Tacer, Assistant Professor, School of Veterinary Medicine, Texas Tech University
(ii) Dr. Ulrich Bickel, Professor, Department of Pharmaceutical Sciences, Texas Tech University
(iii) Dr. Joshua Tropp, Assistant Professor, Department of Chemistry and Biochemistry, Texas Tech University
(iv) Dr. Peter Keyel, Associate Professor, Department of Biological Sciences, Texas Tech University
(v) Dr. Catherine Wakeman, Associate Professor, Department of Biological Sciences, Texas Tech University

Early disease detection is crucial for successful clinical regimens. For instance, identifying cancerous tumors before metastasis enhances patient survival, spotting vulnerable plaques before rupture prevents cardiovascular issues, and detecting toxins associated with pathogens minimizes viral infection side effects. These measures not only improve patient quality of life but also reduce costs. Conventional imaging methods have limitations in early disease detection. Biosensor technology, however, offers sensitive, rapid, and clinic-deployable solutions. Our approach utilizes biomimetic cell membranes on nanoparticles, generating specific signals for various bioanalytes in diseased states. Coupled with surface-enhanced Raman scattering/optical-based nanosensing and data-driven strategies, our nanosensors serve as liquid biopsy and dual assay platforms for swift disease diagnosis.