Nanoparticle-targeted delivery of nonanticoagulant heparin and doxorubicin in doxorubicin-resistant breast cancer

e11599 Background: In comparison to low molecular weight heparin (LMWH), non-anticoagulant heparin (NACH), originally developed in our laboratory, has minimal effects on hemostasis. Encapsulation of chemotherapeutic agents and NACH in biodegradable nanoparticles has tremendous potential in improving survival among the breast cancer patients. Furthermore, custom-made nanoparticles with a targeted moiety on the surface would enable us to increase the efficacy and decrease the adverse effects of doxorubicin. Methods: PLGA-PEG nanoparticles co-encapsulating NACH and doxorubicin were synthesized by double emulsion solvent evaporation method. The in vitro efficacy of these nanoparticles was examined in MCF-7 doxorubicin resistant (MCF-7R) cells using MTT cell viability assay. Confocal microscopy was used to examine the uptake of αvβ3 antibody conjugated nanoparticles in human dermal microvascular endothelial cells (HDMEC), which are known to over express αvβ3 integrins. Results: Size measurement by DLS revealed that these nanoparticles co-encapsulating doxorubicin and heparins to be 200–300 nm in size. Data from the MTT assays in MCF-7R cells showed synergy between NACH and doxorubicin when encapsulated in PLGA-PEG nanoparticles. Confocal imaging in HDMEC cells indicates that these nanoparticles have the potential to be used for site specific delivery to the tumor neovascularization. In vivo data in nude mice xenograft (MCF-7R) are shown in the table below (doses of doxorubicin and NACH injected subcutaneously were 0.625 mg/kg and 2.5 mg/kg body weight, respectively). Significant decrease in tumor weight was observed in the mice xenograft, when treated with αvβ3 conjugated nanoparticles co-encapsulating doxorubcin or to greater extent doxorubicin and NACH compares to its non encapsulated counterparts. Conclusions: These data indicated distinct improvement in the anti-tumor efficacy using αvβ3site directed delivery doxorubicin and NACH encapsulted in PLGA-PEG nanoparticles. [Table: see text] No significant financial relationships to disclose.