Bioengineered photocatalytic nanoprobes for targeting ABCG2/HCP-1 drug efflux/influx pump mediated cancer resistance: a translatable approach for synergizing Oral tumor theranostics
National Institute Of Pharmaceutical Education And Research (Niper-G)
deepakpemmaraju01@gmail.com
Project Overview
Oral cancer is the most common type of malignancy under head and neck cancer. According to the Global Cancer Observatory, the incidence of Oral cancer is predicted to increase by up to 40% by 2040 (Tan et al., 2023). Tobacco use in all its forms, betel quid, and alcohol consumption are well-established risk factors for Oral cancer. Surgery remains the primary treatment approach for Oral cancer. Medical interventions including surgery and chemotherapy have several disadvantages including face abnormalities, resistance to wide cancer therapeutics, cancer heterogeneity and so on hence there is a need to delve for a safer and more effective option to combat the rising deaths due to oral cancer (Akram et al., 2017). Due to the lack of awareness, cases are mostly reported in the later stage. This results in compromised clinical outcomes in patients suffering from oral cancer. Traditional systems of medicines containing plant-based pharmacological moieties were reported to be effective in inhibiting tumors. However, their clinical translation was hindered due to the poor bioavailability and off-target effects. Thus, there is a dire need to develop therapies incorporating bioengineering tools for cost-effective and sustainable oral cancer therapy and detection. One of the key factors reported to be involved in the development of cancer cell resistance mechanisms that can modulate the drug influx/efflux dynamics. Modifying the dynamics drugs efflux/influx transporters like ABCG2 and HCP1, can improve the efficacy of anti-cancer drugs and decrease hypoxia and therefore overcome the resistance in the tumor microenvironment. In addition, it was reported that hyperthermia-mediated mitochondrial ROS can uregulate the influx transporters like HCP-1 and downregulate the ABCG2 thereby enhancing the Photothermal agent's cytotoxicity. Our previous studies have reported organometallic nanoprobes can increase the ROS leading to apoptosis in melanoma. However, it was observed the cancer cells gain resistance to the existing approach by the activation of Heat shock response proteins (HSPs) leading to untargeted and compromised outcomes. Therefore, to target the drug efflux/influx dynamics mediated resistance in the cancer cells, in the current proposal we intend to design light-responsive, photocatalytic copper-based nanoprobes by combining with cancer cells targeting molecule amino levulinic acid (ALA) for enhanced outcomes in oral cancer therapy. The nanoprobes once validated can pave the way for the proof of concept for the development of a nano aerosol-based oral spray based photothermal therapy.