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Pepsin Assisted Doxorubicin Delivery from Mesoporous Silica Nanoparticles Downsizes Solid Tumor Volume and Enhances Therapeutic Efficacy in Experimental Murine Lymphoma.

Prateek SrivastavaSumit Kumar HiraUttam GuptaVivek Kumar SinghRanjeet SinghPankaj PandeyDivesh Narayan SrivastavaRam Adhar SinghPartha Pratim Manna
Published in: ACS applied bio materials (2018)
Pepsin, a digestive enzyme, plays an important role in the metabolism of protein products in the stomach. The pH is regarded as the most pivotal criteria in appraising the pepsin's enzymatic activity. Pepsin is idle at the physiological pH (7.4) but dynamic in the acidic environments of the stomach (pH 2.0-4.0). Inspired by such pH regulatory actions, we have used pepsin as an enhancer, which is attached to silica nanoparticles for the doxorubicin release in the acidic tumor environment. Pepsin enzyme is transitional between the doxorubicin loaded silica nanoparticles and the biotin-avidin cap system, which intercedes the pores. The formed nanoplatform is poised at the physiological pH. However, when switched to low pH simulated conditions, the pepsin become vibrant and cleaves the avidin, rendering the clearance of the path for the diffusion of the drug. This design strategy augmented the drug bioavailability deep inside the solid tumor with enhanced uptake and apoptosis of the tumor cells in experimental lymphoma.
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