Multistage Nanovectors Enhance the Delivery of Free and Encapsulated Drugs

Title:Multistage Nanovectors Enhance the Delivery of Free and Encapsulated Drugs

Volume: 16 Issue: 14

Author(s): Jonathan O. Martinez, Michael Evangelopoulos, Rohan Bhavane, Stefania Acciardo, Francesco Salvatore, Xuewu Liu, Mauro Ferrari and Ennio Tasciotti

Affiliation:

Keywords: Doxorubicin, drug delivery, melittin, micelles, multistage nanovector, nanoparticles.

Abstract: Nanoparticles have considerable potential for cancer imaging and therapy due to their small size and prolonged circulation. However, biological barriers can impede the delivery of a sufficient dose of a drug to the target site, thereby also resulting in the accumulation of toxic compounds within healthy tissues, and systemic toxicity. Multistage nanovectors (MSV) preferentially accumulate on inflamed endothelium, and can thus serve as carriers for drugs and nanoparticles. Herein, we describe the loading of free (i.e., melittin) and nano-encapsulated (i.e., doxorubicin-loaded micelles) drugs into MSV, and report the impact of surface charge and pore size on drug loading. For both drug formulations, negatively charged MSV (i.e., oxidized) with larger pores were shown to retain higher concentrations of payloads compared to positively charged (i.e., APTES-modified) MSV with small pores. Treatment of human umbilical vein endothelial cells (HUVEC) with melittin-loaded MSV (MEL@MSV) resulted in an 80% reduction in cell viability after 3 days. Furthermore, MEL@MSV conjugated with antivascular endothelial growth factor receptor 2 (VEGFR2) antibodies displayed preferential targeting and delivery of MEL to activated HUVEC expressing VEGFR2. Treatment of HUVEC and MCF7 cells with doxorubicin-loaded micelles (DOXNP@MSV) resulted in a 23% and 47% reduction in cell viability, respectively. Taken together, these results demonstrate increased loading of a payload in oxidized, large pore MSV, and effective delivery of free and nano-encapsulated drugs to endothelial and cancer cells.

Cite this article as:

Martinez O. Jonathan, Evangelopoulos Michael, Bhavane Rohan, Acciardo Stefania, Salvatore Francesco, Liu Xuewu, Ferrari Mauro and Tasciotti Ennio, Multistage Nanovectors Enhance the Delivery of Free and Encapsulated Drugs, Current Drug Targets 2015; 16 (14) . https://dx.doi.org/10.2174/1389450115666141015113914