Combining antiangiogenic and chemotherapeutic agents has shown promising clinical benefits in cancer cures when the therapeutic intervention takes into account the tissue and molecular targets. Moreover, the risk of induced drug resistance is minimized when multiple pathways are involved in the treatment regimen, yielding a better therapeutic outcome. Nanodrug delivery systems have proven to be a prudent approach to treating complex disease pathologies. As such, combining antiangiogenic and chemotherapeutic drugs within multimodal nanocarriers synergistically augments the clinical efficiency of the drugs. This study reports the combinatorial efficacy of heparin (Hep), selenium NPs (SeNPs), and doxorubicin (Dox) to inhibit tumor growth and progression. Both Se@Hep-NPs and Se@Hep-Dox-NPs with excellent water dispersity having a size and charge in the range of 250 ± 5 and 253 ± 5 nm and -53 ± 0.4 and -48.4 ± 6.4 mV, respectively, showed strong anticancer potential assessed through in vitro assays like cell viability, specificity, colony formation, and wound scratch in MCF7 cells. Strong synergistic interactions among SeNPs, Hep, and Dox in Se@Hep-Dox-NPs render it to be an antiangiogenic and proapoptotic cancer cell death inducers. In vivo imaging highlights the dual-mode attributes of Se@Hep-NPs with desirable passive tumor targeting and biomedical imaging ability when tagged with Cy7.5, while Se@Hep-Dox-NPs significantly reduce the tumor burden and prolong the longevity of subcutaneous EAC-bearing mice. Histopathology studies reveal no signs of toxicity in major organs. Collectively, these results qualify Se@Hep-Dox-NPs as a plausible clinical therapeutic candidate.
Keywords: Ehrlich ascetic carcinoma; antiangiogenic chemotherapy; apoptosis; drug delivery systems; heparin; nanotechnology; selenium nanoparticles.