Introduction: Tumor adaption to hypoxic stress not only plays a crucial role in tumor malignancy but also protects cancer cells from therapeutic interventions. Hence therapeutic strategies attenuating tumor hypoxia in conjunction with conventional therapies would be an ideal approach. Carbon nano-onions (CNOs) are currently gaining increased interest as a new carbon-based nanomaterial for diverse applications. Although CNO-based nanomaterials are biocompatible and non-toxic compared to other carbon materials, they require surface modifications with biopolymers for improving their biological applications. In this context, manganese oxide (MnO2), a transition metal oxide, nanoparticles have gained significant interest for modulating tumor hypoxia. Their selective interactions with H2O2 can not only result in the generation of oxygen but also assist in decreasing the concentration of H2O2 in the cancer environment. Methods: Here, we developed and investigated the biomedical application of biologically stable CNOs and in situ oxygenic CNO-manganese oxide nanopods (iOCOM) as a novel nanomaterial for hypoxia-responsive image-guided photothermal therapy. Characterization of the iOCOM included measuring dynamic light scattering, FE-TEM, ATR-FTIR. In vitro cell assays were performed to prove hypoxia mitigation, intracellular uptake and cytotoxicity. In vivo MRI and thermal imaging were examined in mice bearing subcutaneous KB tumors following intratumoral administration. Additionally, tumor volume and anti-tumor efficacy was evaluated by analyzing tumor tissues histochemical analysis. Results: The results demonstrate that a single dose of iOCOM was sufficient for complete tumor reduction, with negligible skin ablation. The rapid in situ oxygenation with reduction of H2O2 by iOCOM in hypoxic environments reduced the expression of HIF1-α and assisted in reprogramming the TME. This modulation of the TME had a strong influence on the metastatic parameters of cancer cells. Conclusion: This work demonstrates that acknowledging the role of the TME in cancer progression, metastasis, and development of multi-functional stimuli nanomaterials like iOCOM has great potential for developing efficient cancer therapies. Nanomaterials like iOCOM can be further complexed with other chemotherapeutic drugs to enhance their therapeutic activity during cancer therapy.

Catalase mimicking nanopods targeting tumor adaption to hypoxia potentiate image-guided photothermal therapy

2019 Fall National Meeting

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