Periodic Reporting for period 1 - NANOBOTS (Tumor-Targeting Nanoengineered Bioorthogonal Technologies to Fight Metastatic Cancers)
Período documentado: 2018-11-19 hasta 2020-11-18
Cancers, including advanced lung cancer, melanoma and breast cancer, are an intractable class of disease with unmet needs. Current chemotherapies, however, are compounded with poor efficacy and toxicity issues due to poor targeting of cancer cells against healthy cells. Aimed at improving cancer drug tolerability, maximising dose delivery and reducing side effects, the formal objectives of this MSC Action, termed ‘Nanobots’, have been to develop targeted anti-cancer therapeutics that can track cancer cells selectively and mediate cytotoxic drug release locally. Clinical translation of this unprecedented technology has the potential to provide a highly precise and programmable tool to treat cancers, a feature unattainable by current therapeutics, and will be particularly beneficial for patients with metastatic cancers.
Multifunctional molecular devices armed with cancer-tracking and drug-activating features have been successfully developed to treat metastatic breast cancer in this project. Initially, modular, multifunctional and programmable molecular devices comprising a gold core, a navigator that enables binding to cancer biomarker(s) and an activator that induce drug release of cancer cells were synthetically assembled. These devices were tested against metastatic breast cancer cells and demonstrated good biocompatibility, cancer-targeting, and drug release capabilities. Overall, this project has successfully identified programmed death-ligand 1 (PD-L1) as a viable cancer biomarker for the targeted delivery of the device, established a drug release mechanism in cellular environments, and most importantly, developed an unprecedented cancer-targeting technology that can be programmed to non-invasively target metastatic breast cancer cells with high precision and selectivity without affecting normal cells. In recognition of the clinical potential of this cancer-selective, effective, and safe anti-cancer technology, this project has gained further funding, including a P2D translational funding and ITPA-Wellcome Trust Springboard funding from University of Edinburgh to further develop the cancer-targeting technology to enter clinical translation. The key results of this project have been further disseminated in scientific meetings, conferences, pitch competition, and commercialisation workshops, establishing extensive network within CRUK Edinburgh, Edinburgh Innovations, Eureka Institute for Translational Medicine, and Spin-Up Science.
This MSCA fellowship has allowed the development of an unprecedented technology that can non-invasively target cancers, a feature unattainable by current cancer therapeutics. Aggressive treatment plans are required in conventional chemotherapy to treat advanced metastatic cancers, however systemic distribution of these drugs often leads to poor efficiency in reaching tumour site(s) and indiscriminate targeting of both healthy and cancer cells. This technology is safe, cancer-selective and programmable, and importantly, has immense clinical potential to target-and-treat specific cancer type(s). Beyond this project, further translational and commercialisation efforts have been initiated to further develop the cancer-targeting technology to enter clinical translation. External funding to support preclinical validation, collaboration with clinical partners, as well as support from technology transfer experts have been secured to gain an invaluable entry point to catalyse clinical translation of this technology. Importantly, collaboration with healthcare provider has been initiated to reach end patients to promote the societal impact of this technology, by bridging an important therapeutic efficacy gap currently suffered by cancer patients.