Recent Developments in Nanoparticle Based Targeted Delivery of Chemotherapeutics

M.   Sean   Peach; Sangamesh   G.   Kumbar; Justin   L.   Brown; Cato   T.   Laurencin

Abstract

Cancer is currently responsible for approximately one quarter of all deaths each year in the United States [1]. Decades of refinement to cancer treatment has led to a multimodal approach, which combines surgery with radiation and/or chemotherapy. However, aggressive and advanced stages of cancer are only slightly hindered with drugs and radiation at the cost of considerable patient morbidity. Implementation of nanotechnology can increase the potency and decrease the side effects of chemotherapeutic agents by specifically targeting cancerous tissue. Most nanotechnologies available in the clinical market are nanoparticle (NP) based drug delivery vehicles, which attests to the promise for cancer chemotherapy applications. There is a constantly growing list of materials and synthetic techniques that allow for the creation of NPs with different compositions, sizes, charge, architecture, biodegradability and surface moieties, all of which can be adjusted within each class of particle. Ultimately this design freedom can be utilized to take advantage of cancer pathophysiology and specifically target cancerous tissue. When synthesized to a certain size, NPs delivered systemically can exploit the leaky vasculature of cancerous tumors and passively target the desired cancerous tissue. More precision may be gained by attaching ligands that actively target surface moieties that are expressed to a greater extent by cancer. This review summarizes the progress made in the past 5 years in NP chemotherapeutic delivery with a focus on unique applications of passive, active and external targeting strategies followed by a discussion on what strategy is optimal for cancer chemotherapy.

Keywords: Cancer, chemotherapy, nanotechnology, nanoparticles, drug delivery, passive targeting, enhanced permeability and retention effect, active targeting, xenograft tumor model