Herniarin, a Natural Coumarin Loaded Novel Targeted Plasmonic Silver Nanoparticles for Light Activated Chemo-Photothermal Therapy in Preclinical Model of Breast Cancer

Background: The conventional chemotherapeutic approach for breast cancer involves use of free drug substances that succumb into considerable systemic toxicity. For the past few decades biologically active phytochemicals like coumarins have gained much interest against breast cancer. However, there are lacunas in direct use of these potent biomolecules that impede their pharmacological functions. On the other hand, recent years have also witnessed great advancements in stimuli actuated nanotherapeutics as combined treatment strategies in critical breast cancer cases. Objectives: In this study we formulated novel pentagonal plasmonic silver nanoparticles as folate receptor targeted light responsive nano-delivery platform for a potent coumarin derivative, Herniarin to improve its therapeutic proficiency. Materials and Methods: Primarily, we synthesized plasmonic silver based nanoscopic carrier for herniarin to facilitate its tumor targeted delivery via folate receptors. These formulated nanoparticles (Herniarin quenched, folic acid furnished, HER-FA-AgNPs) were subjected to series of physicochemical tests, followed by detailed in-vitro and in-vivo testing in breast cancer cell lines and DMBA induced breast cancer model in rats, respectively. Results: The pentagonal nanoparticles observed in transmission electron microscopy demonstrated strong plasmonic tunability in the NIR region while its key feature of transforming light into heat energy when exposed to laser (800 nm) allowed photothermal therapy to supplement the chemotherapeutic potential of Herniarin as illustrated in various in-vitro studies. The in-vivo studies including detailed cellular investigations of breast tissues through Field Emission Scanning Electron Microscope and histopathology reflected the improved outcome of combined therapeutic modalities (hyperthermia + chemotherapy) achieved by HER-FA-AgNPs. Conclusion: Thus, these novel nanoparticles may serve as an efficient as well as safe drug-disposing vehicle for combined and strategic therapy of breast cancer.