title: Targeting Cancer using Polymeric Nanoparticle mediated Combination Chemotherapy.
abstract: Cancer forms exhibiting poor prognosis have been extensively researched for therapeutic solutions. One of the conventional modes of treatment, chemotherapy shows inadequacy in its methodology due to imminent side-effects and acquired drug-resistance by cancer cells. However, advancements in nanotechnology have opened new frontiers to significantly alleviate collateral damage caused by current treatments via innovative delivery techniques, eliminating pitfalls encountered in conventional treatments. Properties like reduced drug-clearance and increased dose efficacy by the enhanced permeability and retention effect deem nanoparticles suitable for this application. Optimization of size, surface charge and surface modifications have provided nanoparticles with stealth properties capable of evading immune responses, thus deeming them as excellent carriers of chemotherapeutic agents. Biocompatible and biodegradable forms of polymers enhance the bioavailability of chemotherapeutic agents, and permit a sustained and time-dependent release of drugs which is a characteristic of their composition, thereby providing a controlled therapeutic approach. Studies conductedin vitroand animal models have also demonstrated a synergism in cytotoxicity given the mechanism of action of anticancer drugs when administered in combination providing promising results. Combination therapy has also shown implications in overcoming multiple-drug resistance, which can however be subdued by the adaptable nature of tumor microenvironment. Surface modifications with targeting moieties can therefore feasibly increase nanoparticle uptake by specific receptor-ligand interactions, increasing dose efficacy which can seemingly overcome drug-resistance. This article reviews recent trends and investigations in employing polymeric nanoparticles for effectively delivering combination chemotherapy, and modifications in delivery parameters enhancing dose efficacy, thus validating the potential in this approach for anticancer treatment.
authors.affiliation: Biomedical Engineering and Biotechnology Program, University of Massachusetts, Lowell, USA.
authors.forename: Aniket
authors.initials: A
authors.lastname: Gad
authors.affiliation: Biomedical Engineering and Biotechnology Program, University of Massachusetts, Lowell, USA.
authors.forename: Janel
authors.initials: J
authors.lastname: Kydd
authors.affiliation: Department of Chemical Engineering, University of Massachusetts, Lowell-1 University Ave, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Piel
authors.affiliation: Biomedical Engineering and Biotechnology Program, University of Massachusetts, Lowell, USA; Department of Chemical Engineering, University of Massachusetts, Lowell-1 University Ave, USA.
authors.forename: Prakash
authors.initials: P
authors.lastname: Rai
keywords: Biocompatibility; Biodegradability; Biopolymers; Controlled release; Drug delivery; Enhanced permeability and retention; Multi-drug resistance; Nanomedicine; Oncology; Receptor mediated endocytosis