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Polymer Prodrug Conjugation to Tumor Homing Mesenchymal Stem Cells

Abstract
Toxicity resulting from systemic administration continues to limit the effectiveness of modern chemotherapeutics. Administered drugs and biologics damage vital organs via off target effects while in circulation, decreasing the maximum tolerated dose and preventing the use of more effective drug concentrations. Many therapeutic agents are additionally constrained by a narrow therapeutic index, requiring delicate balance between toxicity and loss of efficacy. With dose remaining a critical determinant of efficacy, the inability to utilize increased drug concentrations due to toxicity prevents the full exploitation of the drug’s therapeutic effect. While exploitation of the enhanced permeability and retention effect has been somewhat successful in targeting nanoparticles to tumors via passive accumulation, elevated tumor pressure and poor drug penetrance prevent a significant improvement in therapeutic effect. Here we describe the conjugation of polymer prodrugs to tumor homing mesenchymal stem cells as a novel approach to chemotherapeutic drug delivery. The utilization of an actively homing cellular vehicle for effective drug delivery against the pressure gradient has the potential to improve drug penetration of the tumor while reducing systemic toxicity and improving drug efficacy.
Type
campus
article
thesis
Date
2012-01-01
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