Research Directions

Research Direction #1 : Biomimetic Nanoparticles with Tunable Features for Targeted Delivery of Nanotherapeutics.
For conventional nanoparticle (NPs)-based therapeutics to show desired effects, precise delivery to targeted sites is imperative.  However, NPs being exogenous materials are easily recognized by the immune systems and marked by clearance by Kupffer cells, severely impeding the clinical applications of NPs. To overcome this bottleneck, we have demonstrated that an active cell membrane coating derived from natural cells (such as red blood cells) circumvents this issue. The cell membrane coating bestows NPs with intriguing features including immune escape, long blood circulation, and ligand insertion for solid tumor targeting. Building upon this, we will develop microfluidic-assisted strategies that will allow us to rationally design biomimetic NPs having tunable biomimetic properties (deep tumor penetration, enhanced pharmacokinetics, reduced protein corona formation), molecular imaging agents (organic dyes, plasmonic NPs), and therapeutic cargos (small molecule drugs, mRNA therapeutics). 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)

Overall research vision. Our research goal is to combine the unique characteristics of natural biomaterials (cells, membrane fragments) with nanoengineering design principles to make disease-specific nanosensors for image-guided interventions and rapid diagnosis of diseases like cancer, cardiovascular diseases, and bacterial pathogenesis. To accomplish this, my research program will culminate in developing and validating these nanosensors using polymeric engineering principles, cellular and molecular biology tools, and clinically relevant animal models. We are interested in demonstrating their applications in healthcare diagnostics and therapeutics, eventually pushing them into clinics.  

Research Direction #2 : Biomimetic Nanoparticles for Multi-Modal Image-Guided Surgical Interventions for Cancer.

Nanotechnology has transformed image-guided surgery, offering precision and minimally invasive procedures. Nano-sized imaging agents hold the potential to enhance visualization of pathological regions, but many lack clinical validation from a surgeon's perspective. To address this, we collaborate closely with surgeons to design imaging agents for cancer surgery, considering the surgical context. For example, real-time fluorescence imaging improves tumor resection outcomes, especially in heterogeneous tumors, necessitating the detection of multiple overexpressed cancer biomarkers with precision. To overcome the limitations of multiple excitation wavelengths, we've created biomimetic nanoparticles targeting folate and αυβ3 integrins using a single excitation wavelength camera sensors as shown in our pre-clinical evaluation covering in vitro tumor cells, ex vivo tumor cell-mimicking models, and in vivo mouse xenografts. These nanoparticles offer improved biocompatibility, extended circulation, reduced liver uptake, specific fluorescence enhancement in tumors, and insights into cancer progression. Additionally, we have designed multifunctional nanoparticles that combine the benefits of photoacoustic imaging with its high penetration depth and SERS spectroscopy, offering real-time spectroscopic information during intraoperative resection procedures. As a part of a team, we developed nature-inspired camera sensor systems that have been deployed in clinical trials for fluorescence-guided cancer surgeries and for pre-clinical validation, enabling the detection of ultraviolet signatures from tumor cells.

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 : Rationally Designed Biomimetic Nanosensors as Liquid Biopsy Platforms for Early Disease Diagnosis & Monitoring
The success of a clinical regimen is highly dependent on the early detection of diseases. For example, (i) detection of cancerous tumors before metastases can improve the survival rate of patients, (ii) identifying vulnerable plaques before rupture can prevent thrombosis and therefore lower the risk of cardiovascular diseases (CVD), and (iii) early identification of toxins associated with pathogens and can allow circumventing the severe side effects of viral infections. Moreover, these culminate in improving the patient’s quality of life and reducing associated costs. Conventional imaging methods like computed tomography or magnetic resonance imaging used for (i) and (ii) rely on imaging agents that can produce an enhancement in signal or contrast in a diseased microenvironment. These are beneficial for imaging physiological processes, however, these are unreliable for detecting and grading diseases efficiently at an early stage of the disease. Common diagnostic techniques employed for (iii) such as immunology-based technique (ELISA) can provide sensitive, qualitative, and quantitative data but require trained staff, are time-consuming, and usually have sensitivity issues.

To overcome these bottlenecks, biosensor technology has grown exponentially in the past decade proving its capability in providing sensitive and reliable results with much shorter analysis times and with the added benefit of being deployed at clinics. However, most of them rely on designing disease-specific targeting moieties like apatamers and peptides that can be tedious and time-consuming. We serendipitously found that biomimetic cell membranes coated on nanoparticles can generate a specific “spectral” signal in response to a different bioanalytes in a diseased state. Leveraging such semi-specific cell membrane coating with our expertise in surface-enhanced Raman scattering (SERS)/optical-based nanosensing and data-driven science strategies (advanced analytics, machine learning, and deep learning), our group will rationally use these nanosensors as liquid biopsy platforms and SERS/Optical-lateral flow assay dual platforms for rapid disease diagnosis..

Reference publications: (+ denotes co-first authorship)
(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. Xing Wang, Research Associate Professor, Departments of Chemistry and Bioengineering, University of Illinois at Urbana-Champaign
(vi) Dr. Li Lin, Assistant Professor, Department of Biomedical Engineering, Shanghai Jiao Tong University, China