Sourabh Mehta

All Publications

• Scalable Synthesis of Calcium Fluoride Nanoparticles as a Novel Ultrasound Contrast Agent for Imaging Tumor Targeted Delivery of Therapeutics. Chemical & biomedical imaging Thangudu, S., Natarajan, A., Mehta, S., Devarakonda, K. P., Massoud, T. F., Paulmurugan, R. 2026; 4 (6): 1202-1213

  Abstract

  Ultrasound (US) imaging is one of the most widely used noninvasive diagnostic techniques in clinical practice due to its safety, real-time capability, and cost-effectiveness. However, traditional B-mode imaging provides limited information with low sensitivity. Recently microbubble (MB)-based contrast agents have been employed to enhance contrast signals while also facilitating the imaging of molecular targets in target tissues or pathological locations. Currently available MBs face several limitations, including large size (typically 1-10 μm), limited ability to penetrate beyond blood vessels, poor in vivo stability, susceptibility to gas leakage, and high production costs, which collectively hinder their clinical efficiency and applicability. To address these limitations, we developed calcium fluoride (CaF2) nanoparticles (NPs) using a scalable synthesis process as a next-generation ultrasound contrast agent via a coprecipitation method using citrate as a stabilizing agent. The synthesized NPs exhibited a uniform size distribution (∼100 nm) with consistent reproducibility during scalable production conditions. Notably, CaF2 NPs generated substantially better contrast-enhanced ultrasound signals under acidic conditions (pH 5.5) than at neutral pH (7.2). The porous structure of the CaF2 NPs enabled us to efficiently load doxorubicin with the loading efficiency of 29.3 ± 5% and controlled intracellular delivery in MDA-MB-231 breast cancer cells in vitro. In vivo studies using an orthotopic breast cancer model demonstrated a pronounced pH-responsive ultrasound contrast signal following intravenous administration of CaF2 NPs (15 mg/kg). Tumor signal intensity increased ∼25-fold compared to controls at 1 h postinjection, with contrast persisting up to 5 h, dramatically outperforming conventional microbubbles that typically dissipate within 10 min. Biosafety analyses confirmed excellent hemocompatibility and no detectable organ toxicity. To the best of our knowledge, this is the first report of CaF2 NPs functioning as a US contrast agent for in vivo tumor imaging and drug delivery. Overall, we identify CaF2 NPs as safe, long-lasting, and multifunctional US contrast agents with integrated drug delivery capability, offering a promising platform for advanced ultrasound imaging and theranostic applications.

  View details for DOI 10.1021/cbmi.5c00259

  View details for PubMedID 42358794

  View details for PubMedCentralID PMC13291996

• Scalable Synthesis of Calcium Fluoride Nanoparticles as a Novel Ultrasound Contrast Agent for Imaging Tumor Targeted Delivery of Therapeutics CHEMICAL & BIOMEDICAL IMAGING Thangudu, S., Natarajan, A., Mehta, S., Devarakonda, K., Massoud, T. F., Paulmurugan, R. 2026

  View details for DOI 10.1021/cbmi.5c00259

  View details for Web of Science ID 001671622900001

• Structural Characterization and AI-Enhanced Modeling of a Broadly Neutralizing Camelid Antibody Against SARS-CoV-2 Variants ADVANCED THERAPEUTICS Hanack, K., Orzel, U., Schlor, A., Mehta, S., Krishnan, A., Filipek, S., Patel, R., Joshi, M., Hoffmann, M., Pohlmann, S., Joshi, C., Liepmann, D., Paulmurugan, R., Renugopalakrishnan, V. 2025

  View details for DOI 10.1002/adtp.202500244

  View details for Web of Science ID 001596295300001

• Autologous extracellular vesicles derived from conjunctival squamous cell carcinoma deliver therapeutic microRNAs to induce apoptosis in originating cancer. Journal of materials chemistry. B Thangudu, S., Mehta, S., Dhowre, H. S., Bojic, S., Haghverdi, G., Wu, A. Y., Massoud, T. F., Paulmurugan, R. 2025

  Abstract

  There are significant challenges in treating advanced and recurrent conjunctival squamous cell carcinoma (cSCC). Therapeutic miRNAs directed at cSCC may have anticancer potential, but questions remain regarding efficiency of their targeted delivery. In this study, we address limitations of miRNA delivery by engineering autologous extracellular vesicles (EVs) of ∼130 nm sizes derived from cSCC UMSCC9 cells and tumors (cSCC-EVs) using a microfluidic based reconstruction system. We ICG-labelled these cSCC-EVs to enable subsequent tracking of miRNA delivery to tumors in vivo, and loaded them with Cy5-labelled antimiR-10b to monitor delivery efficiency of miRNA-ICG-EVs in vitro and in vivo using optical imaging. We characterized miRNA-ICG-EVs and confirmed their successful internalization into UMSCC9 cells in culture using confocal microscopy and FACS analysis. In an orthotopic subconjunctival implantation mouse model of cSCC, fluorescence signals in miRNA-ICG-EV-treated mice remained strong at tumor locations even 96 h after in vivo administration. We found in mice treated with miRNA-ICG-EVs that there were significantly higher levels of both intracellular Cy5-antimiR-10b on ex vivo tumor histological analysis, and antimiR-10b-induced apoptotic cells in tumors on TUNEL assay, as well as a significant reduction in tumor growth on in vivo optical coherence tomography and ex vivo H&E staining. Taken together, we show that targeted delivery of therapeutic miRNAs encapsulated within autologously-derived EVs may have substantial potential in future adjunctive clinical treatment for cSCC. This novel approach may provide a minimally invasive and personalized strategy that could be combined with topical chemotherapy in future clinical applications.

  View details for DOI 10.1039/d5tb00587f

  View details for PubMedID 40642822

• Ultrasound-assisted targeted delivery of drug-loaded nanoparticles for retinoblastoma treatment Park, J., Mehta, S., Paulmurugan, R., Dahl, J. J., IEEE IEEE. 2024

  View details for DOI 10.1109/UFFC-JS60046.2024.10793607

  View details for Web of Science ID 001428150100117

• An Ultrasound-Responsive Theranostic Cyclodextrin-Loaded Nanoparticle for Multimodal Imaging and Therapy for Atherosclerosis SMALL Mehta, S., Bongcaron, V., Nguyen, T. K., Jirwanka, Y., Maluenda, A., Walsh, A. P. G., Palasubramaniam, J., Hulett, M. D., Srivastava, R., Bobik, A., Wang, X., Peter, K. 2022; 18 (31): e2200967

  Abstract

  Atherosclerosis is a major cause of mortality and morbidity worldwide. Left undiagnosed and untreated, atherosclerotic plaques can rupture and cause cardiovascular complications such as myocardial infarction and stroke. Atherosclerotic plaques are composed of lipids, including oxidized low-density lipoproteins and cholesterol crystals, and immune cells, including macrophages. 2-Hydroxypropyl-beta-cyclodextrin (CD) is FDA-approved for capturing, solubilizing, and delivering lipophilic drugs in humans. It is also known to dissolve cholesterol crystals and decrease atherosclerotic plaque size. However, its low retention time necessitates high dosages for successful therapy. This study reports CD delivery via air-trapped polybutylcyanoacrylate nanoparticles (with diameters of 388 ± 34 nm) loaded with CD (CDNPs). The multimodal contrast ability of these nanoparticles after being loaded with IR780 dye in mice is demonstrated using ultrasound and near-infrared imaging. It is shown that CDNPs enhance the cellular uptake of CD in murine cells. In an ApoE-/- mouse model of atherosclerosis, treatment with CDNPs significantly improves the anti-atherosclerotic efficacy of CD. Ultrasound triggering further improves CD uptake, highlighting that CDNPs can be used for ultrasound imaging and ultrasound-responsive CD delivery. Thus, CDNPs represent a theranostic nanocarrier for potential application in patients with atherosclerosis.

  View details for DOI 10.1002/smll.202200967

  View details for Web of Science ID 000811802900001

  View details for PubMedID 35710979