Immune Cell-Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery

Open Access
Author:
Su, Yixue
Graduate Program:
Bioengineering
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
March 01, 2016
Committee Members:
  • Jian Yang, Thesis Advisor
  • Justin Lee Brown, Thesis Advisor
  • Yong Wang, Thesis Advisor
Keywords:
  • Nanoparticles
  • Immune cells
  • Theranostics
  • Melanoma
  • Drug Delivery
Abstract:
Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell-mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic aspects. Herein, by taking advantage of innate immune cell’s ability to target tumor cells, we developed a novel drug delivery system by using macrophages as both nanoparticle-carriers and navigators to achieve cancer-specific drug delivery. Firstly, we fabricated theranostic nanoparticles from a unique biodegradable photoluminescent poly (lactic acid) (BPLP-PLA), which inherently possesses strong tunable fluorescence, biodegradability, and cytocompatibility. In order to minimize the damage of cancer drugs to carrier immune cells and other healthy cells, a BRAF V600E mutant melanoma specific drug (PLX4032) was loaded into BPLP-PLA nanoparticles. Muramyl tripeptide (MTP) was also conjugated onto the nanoparticles in order to improve the nanoparticle loading efficiency. The resulting nanoparticles were internalized within macrophages, which were tracked via the intrinsic fluorescence of BPLP-PLA to demonstrate potential in imaging-based diagnosis and therapy. Nanoparticle-carrying macrophages were able to bind with and deliver drugs to melanoma cells under both static incubation and dynamic shear-flow conditions. Finally, pharmacological studies indicated that the delivered PLX4032 loaded nanoparticles did not show cytotoxicity against macrophages, while effectively killing melanoma cells. Our “smart” immune cell-mediated drug delivery system demonstrates the advancement of intrinsically traceable and targeted cancer nanomedicine.