In Situ Oxygenic Nanopods Targeting Tumor Adaption to Hypoxia Potentiate Image-Guided Photothermal Therapy.

Tumor adaption to hypoxic stress not only plays a crucial role in tumor malignancy but also can protect cancer cells from therapeutic interventions. Hence, therapeutic strategies attenuating tumor hypoxia in conjunction with conventional therapies may be an ideal approach. Here, we report the application of in situ oxygenic carbon nano-onion (CNO)/manganese oxide nanopods (iOCOMs) as novel theranostic photothermal transducers to neutralize the oncogenic influence of the hypoxic tumor microenvironment (TME). The developed onion-ring-shaped carbon nanoparticles or carbon nano-onions (CNOs) and iOCOM nanopods (CNO embedded in MnO2 nanosheets) were biologically stable and nontoxic and showed photothermal activity under near-infrared laser irradiation (808 nm). In addition, iOCOM assisted in the dismutation of hydrogen peroxide (H2O2), a potentially toxic reactive oxygen species that is secreted excessively by cancer cells in the hypoxic TME, resulting in in situ oxygenation and repolarization of the hypoxic TME to normoxia. The manganese ions released from iOCOM during the catalysis of H2O2 assisted in TME-responsive T1 magnetic resonance imaging (MRI). The in situ oxygenation by iOCOM in the hypoxic TME downregulated the secretion of hypoxia-inducible factor 1-α, which subsequently interfered with the cancer cell proliferation, favored tumor angiogenesis, and most importantly prevented metastatic epithelial-to-mesenchymal transition of tumor cells. Collectively, this work presents a new paradigm for antitumor strategies by targeting the tumor adaption to hypoxia in combination with photothermal therapy.

Anticancer activity of Arkeshwara Rasa - A herbo-metallic preparation.

INTRODUCTION: Though metal based drugs have been prescribed in Ayurveda for centuries to treat various diseases, such as rheumatoid arthritis and cancer, toxicity of these drugs containing heavy metal is a great drawback for practical application. So, proper scientific validation of herbo-metallic drugs like Arkeshwara Rasa (AR) have become one of the focused research arena of new drugs against cancers. AIM: To investigate the in vitro anticancer effects of AR. MATERIALS AND METHODS: Anticancer activity of AR was investigated on two human cancer cell lines, which represent two different tissues (pancreas and skin). Lactate dehydrogenase (LDH) assay for enzyme activity and trypan blue assay for cell morphology were performed for further confirmation. RESULTS: AR showed potent activity against pancreatic cancer cells (MIA-PaCa-2). LDH activity confirmed that AR was active against pancreatic cancer cells. Finally, it was observed that AR exhibited significant effects on cancer cells due to synergistic effects of different compounds of AR. CONCLUSION: The study strongly suggests that AR has the potential to be an anticancer drug against pancreatic cancer.