The cytotoxic effect of nanparticles delivered to the periphery of 3-dimensional tumor models

Hillary K. A Holback, Purdue University

Abstract

To deliver chemotherapeutic drugs to tumors, a drug delivery vehicle should overcome several challenges. The vehicle should stably retain the drug until it reaches tumor tissues and release the drug upon arrival at the target tissues. A nanoparticle (NP) that conditionally releases anticancer drug doxorubicin (DOX) was developed. This NP, referred to as PAMAM-SS-DOX or PAMAM-SS-NAC-DOX, consists of cationic polyamidoamine (PAMAM) dendrimer conjugated to DOX via a disulfide bond. The cationic charge allows NP interaction with negatively charged cells and the disulfide bond allows conditional, intracellular release of DOX via glutathione (GSH). In cases where chemotherapeutic drug delivery systems have been delivered to the tumor site in vivo, it is largely unknown or difficult to assess how NP intratumoral distribution affects NP cellular uptake and any subsequent cytotoxicity in tumors. Consequently, 3-dimensional (3D) tumor models were developed as tools for the evaluation of drug delivery system efficacy in vitro, in order to implement more effective NP chemotherapy in vivo. Consisting of human ovarian tumor cells (SKOV-3), “cells in collagen” and “cells in spheroid” 3D tumor models were developed to simulate common physiological barriers (the presence of extracellular matrix and high cell density, respectively) encountered by NP drug delivery systems after extravasation to the tumor site. The cytotoxicity of cisplatin (CDDP) and hyaluronic acid (HA) NPs carrying platinum (Pt-HA NPs) was investigated in both “cells in collagen” and “cells in spheroid” tumor models.

Degree

Ph.D.

Advisors

Yeo, Purdue University.

Subject Area

Pharmacy sciences

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