Biology subjects

Mahajan, S. D.

Publications and source records attributed to Mahajan, S. D..

5 recordsLinked to original sources

bioRxiv2026

A PSMA-Targeted Up-conversion Nanoplatform for Deep-Tissue dual activation Photodynamic and Sonodynamic Therapy of Castration Resistant Prostate Cancer.

Photodynamic therapy (PDT) for prostate cancer is limited by the shallow penetration of visible light into deep-seated tumors. In contrast, sonodynamic therapy (SDT) enables noninvasive deep-tissue activation using ultrasound, while near-infrared photodynamic therapy (NIR-PDT) enhances tissue penetration through up-conversion-mediated activation. Based on these advantages, we developed a prostate-specific membrane antigen (PSMA)-targeted nanotheranostic platform (UCNPs@mSiO2/HPPH@TCS) to compare NIR-PDT and SDT in vitro for penetration-enhanced and targeted prostate cancer therapy. The nanoformulation consists of NaYF4:Yb3+, Er3+ up-conversion nanoparticles coated with mesoporous silica for high loading of HPPH (Photochlor), which functions as both photosensitizer and sonosensitizer, and a PSMA-targeted chitosan shell for selective tumor targeting. Physicochemical characterization confirms a uniform core-shell structure ([~]63 nm). Tissue-mimicking depth studies demonstrate that SDT and NIR-PDT achieve greater penetration than conventional 665 nm PDT in thicker tissue layers. Intracellular reactive oxygen species (ROS) analysis shows that SDT generates higher total ROS levels, whereas NIR-PDT produces greater singlet oxygen generation. Three-dimensional spheroid models further validate efficacy, demonstrating rapid spheroid collapse via apoptosis, with SDT inducing earlier apoptosis and more uniform penetration than PDT. Collectively, the results suggest SDT provides superior overall therapeutic efficacy compared with NIR-PDT, highlighting the potential of this nanoplatform for precision prostate cancer therapy.

cancer biology↗

bioRxiv2025

Oxidative Stress, Hypoxia and Cellular Metabolism: Unraveling the Effects of Fentanyl on Lung Cancer Cells

Fentanyl, a widely used opioid analgesic for cancer pain management, is effective but requires cautious administration due to its potential for respiratory depression. Beyond its analgesic properties, fentanyls broader impact on cancer biology and biochemical alterations in lung carcinoma cells remains underexplored. This study investigates fentanyls influence on oxidative stress, mitochondrial function, hypoxia-inducing factors, apoptosis, and cytokine production in A549 lung cancer cells. Our findings reveal that fentanyl increases reactive oxygen species (ROS) generation, disrupts cellular homeostasis, induces DNA damage, and alters key signaling pathways, potentially affecting tumor metabolism and progression. Our "Ramanomics" data further highlight fentanyl-driven changes in key ions (inorganic phosphate, calcium) and biomolecules (glycogen, phospholipids, proteins, nucleic acids, and enzymes) at subcellular mitochondrial levels. These insights contribute to understanding fentanyls mechanistic impact on lung cancer progression and may inform optimized therapeutic strategies. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/665412v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1fb7aaaorg.highwire.dtl.DTLVardef@13255deorg.highwire.dtl.DTLVardef@1a398cdorg.highwire.dtl.DTLVardef@184d63e_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Blast Traumatic Brain Injury Induces Long-Term Alterations in Inflammatory Gene Expression in Chinchilla Brains

Blast traumatic brain injury (bTBI) due to high-intensity impulsive noise exposure from explosions and munitions exposure is highly prevalent among military personnel, which leads to diffuse brain injury resulting in a spectrum of brain dysfunction and cognitive deficits. The resultant prolonged neuroinflammation and consequent failure of inflammation resolution is a key contributor to long-term complications, including post-traumatic stress disorder and early-onset of neurodegenerative disease; however, there is little evidence for the duration and extent of long term neuroinflammation in distinct brain regions. To investigate this, due to human-like audiogram, we use chinchillas as an in-vivo bTBI model to analyze the relative gene expression of inflammatory markers (TNF, TGF{beta}2, Gal1, HSP90, S100B, NRGN, MAPK14, IL8, NFL, and BDNF) in the hippocampus, striatum, and higher centers of the auditory pathway 90 days following varying intensities of blast exposures (144 dB, 155 dB, and 172 dB sound pressure level). Our study revealed aberrant gene expression across all analyzed brain regions and all injury conditions; however, no specific pattern emerged. Many of the inflammatory markers were downregulated, suggesting a possible attempt by the brain to overcome prior inflammation. Conversely, the hippocampus, striatum, inferior colliculus, and medial geniculate body all exhibited upregulation of inflammatory markers, including the TBI prognostic marker, S100B. Thus, chinchilla brains exhibit evidence of prolonged neuroinflammation 90 days following injury, even during mild blast exposure. Ultimately, the observed alterations in the gene expression of inflammatory markers may contribute to the long-term neurological dysfunction and neurodegenerative disease experienced by veterans and other bTBI patients.

neuroscience↗

bioRxiv2022

Effective drug combinations targeting driver KRAS mutations in non-small cell lung cancer

1.Pharmacogenomics is a rapidly growing field with the goal of providing personalized care to every patient. Previously, we developed the Computational Analysis of Novel Drug Opportunities (CANDO) platform for multiscale therapeutic discovery to screen optimal compounds for any indication/disease by performing analytics on their interactions with large protein libraries. We implemented a comprehensive precision medicine drug discovery pipeline within the CANDO platform to determine which drugs are most likely to be effective against mutant phenotypes of non-small cell lung cancer (NSCLC) based on the supposition that drugs with similar interaction profiles (or signatures) will have similar behavior and therefore show synergistic effects. CANDO predicted that osimertinib, an EGFR inhibitor, is most likely to synergize with four KRAS inhibitors.Validation studies with cellular toxicity assays confirmed that osimertinib in combination with ARS-1620, a KRAS G12C inhibitor, and BAY-293, a pan-KRAS inhibitor, showed a synergistic effect on decreasing cellular proliferation by acting on mutant KRAS. Gene expression studies revealed that MAPK suppression is a key correlate of decreased cellular proliferation following treatment with KRAS inhibitor BAY-293, but not treatment with ARS-1620 or osimertinib. Our precision medicine pipeline may be used to identify compounds capable of synergizing with inhibitors of KRAS G12C, and to assess their likelihood of becoming drugs by understanding their behavior at the proteomic/interactomic scales.

bioinformatics↗

bioRxiv2022

Dynamic changes in the niche and transcription trigger early murine and human pluripotent stem cell-derived liver organogenesis

The shift from collective migration to differentiation is a crucial process in epithelial biology but recreating this intricate transition has thus far proved elusive. We provide experimental, mechanistic, in vivo, and bioinformatic data supporting an undoubtable link between human pluripotent stem cell (hPSC)- derived collectively migrating hepatoblasts (MHB), and transcriptionally mature, functional hPSC- hepatocytes (HEPs), which incorporates two unrecognized steps. The protocol induces FOXA-dependent induction of HBs, leading to TBX3-positive, YAP-TEAD active MHBs which provide a transcriptional match with murine liver E9.5 MHBs. Simple cultivation changes trigger MHBs to rapidly form functional day 18 HEPs, predicted by a deep-learning designed gene circuit, resulting in a [~]236% fold- increase in maturation (PACNet), on par with the highest score, but with enhanced global transcriptional shaping. Overall, incorporating the MHB to HEP transition establishes a new, unrecognized, and highly efficient mechanism for differentiation that can be cumulatively integrated with existing methods to overcome barriers to maturation.

bioengineering↗