“The incidence of cancer is among the leading causes of death worldwide, with more than 29 million people expected to be diagnosed by 2040. Despite advancements in cancer therapies, current immunotherapeutic approaches face challenges such as limited efficacy and off-target effects. To address these challenges, this study focuses on enhancing the efficacy of immunotherapeutics in the treatment of non-small cell lung cancer (NSCLC) through combination with a TGF- β inhibitor. A novel nanosystem was developed by co-loading galunisertib, a TGF-β inhibitor, and nivolumab, a PD-1 inhibitor, into spherical nanoparticles composed of PLGA derivatives conjugated with anti-EGFR for targeted delivery. In vitro characterization studies, including the nanoparticle size, zeta potential, morphology, drug release, toxicity evaluation in healthy and tumor cells, and T cell immune responses, demonstrated promising results. Based on these findings, in vivo studies were conducted on humanized mice that developed heterotopic xenograft tumors. In the concept of in vivo studies, biodistribution studies revealed that antibody-conjugated nanoparticles exhibited higher tumor accumulation compared to the control group. In vivo results further showed that co-drug loaded nanoparticles targeted to the tumor were more effective in reducing tumor size compared to non-targeted nanoparticles, achieving efficacy comparable to the combination of free drug and targeting ligand.”
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