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First advantage is the enzymatic amplification; nanoparticles filled with enzymes, when localized to tumor, are capable of producing several orders more cytotoxic drug than can be delivered using drug-loaded nanoparticles. Skip to content Targeted enzyme prodrug therapy, in which an exogenous enzyme is used to locally convert a non-toxic prodrug into a potent toxic agent at the site of a tumor, has been a conceptually attractive alternative to the toxicities that limit systemic chemotherapies. While cytotoxic drugs, when injected intra-tumorally quickly diffuse out from the tumor, SHELS get retained within tumor tissue for extended durations owing to their large size. However, enzyme prodrug therapies have encountered numerous obstacles that have limited their development. When given intravenously iv , SHELS accumulate in tumors through the enhanced permeation and retention phenomenon EPR associated with leaky tumor vasculature. However, enzyme prodrug therapies have encountered numerous obstacles that have limited their development. While cytotoxic drugs, when injected intra-tumorally quickly diffuse out from the tumor, SHELS get retained within tumor tissue for extended durations owing to their large size. First advantage is the enzymatic amplification; nanoparticles filled with enzymes, when localized to tumor, are capable of producing several orders more cytotoxic drug than can be delivered using drug-loaded nanoparticles. Subsequently, prodrug is administered systemically where it is converted to cytotoxic drug by the enzymes within SHELS localized to tumor and metastatic lesions. Skip to content Targeted enzyme prodrug therapy, in which an exogenous enzyme is used to locally convert a non-toxic prodrug into a potent toxic agent at the site of a tumor, has been a conceptually attractive alternative to the toxicities that limit systemic chemotherapies. The outside of the SHELS are decorated with PEG to extend circulation time as well as a peptide mimetope ligand for assisted clearance with a monoclonal antibody such as trastuzumab. Once sufficient accumulation obtained, SHELS still present systemically are cleared by addition of monoclonal antibody which binds to the mimetope peptide on SHELS surface and enhances their clearance by the reticuloendothelial system and tissue macrophages. Skip to content Targeted enzyme prodrug therapy, in which an exogenous enzyme is used to locally convert a non-toxic prodrug into a potent toxic agent at the site of a tumor, has been a conceptually attractive alternative to the toxicities that limit systemic chemotherapies. Third, off-target particles loaded with enzymes potentially cause reduced side effects because enzymes cleared by the macrophages substantially lose their activity within the endosomes. First advantage is the enzymatic amplification; nanoparticles filled with enzymes, when localized to tumor, are capable of producing several orders more cytotoxic drug than can be delivered using drug-loaded nanoparticles. When given intravenously iv , SHELS accumulate in tumors through the enhanced permeation and retention phenomenon EPR associated with leaky tumor vasculature.

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