A new therapy in oncology? Nano-catalysts that kill cells and the tumor microenvironment

Abstract:

A wide variety of therapies against cancer have been developed in the 8 decades. In spite of this, cancer is still of the leading causes of death: By current estimates, by 2030 over 20 million new cases will be diagnosed yearly, and cancer will cause 13 million deaths worldwide. Given the magnitude of this effort, it is noteworthy that Heterogeneous Catalysis, a field recognized for being able to facilitate chemical reactions with high selectivity, has been scarcely explored in oncology. This may be about to change: The emerging field of bio-orthogonal catalysis is providing new ways to tune the chemistry of complex biological systems, with a myriad of potential applications in diagnosis and therapy.
However, using catalysis as an effective tool against cancer has been restricted due to three main challenges: First, catalysts must be able to perform effectively against cancer, under the conditions prevailing in the tumor environment. Also, the catalyst has to be protected from the environment (e.g. from poisoning from sulphur-containing biomolecules). Second, the catalyst must be delivered selectively (or at least preferentially) to the tumor. This is also a formidable challenge, since current methods that rely on the EPR effect or even targeted delivery, present a very low delivery efficiency. For this reason, a variety of alternative delivery methods (e.g. Trojan Horse strategies) are being investigated. Third, ideally the catalyst should be activated only at the tumor site, to avoid side effects in healthy cells. For this, a variety of possibilities exist such as NIR-based activation, environment-related activation, etc.
In this talk we will present recent results obtained in the ongoing ERC Advanced Grant CADENCE. It will discuss recent advances regarding each of the above areas, (what catalysts can be used, which reactions, how to deliver them to the tumor using exosomes and other extracellular vesicles or even whole cells as carriers, and how to activate the catalyst once it reaches its target).

References
1. “Cancer-derived exosomes loaded with ultrathin Palladium nanosheets for targeted bioorthogonal catalysis”, M. Sancho-Albero, et al. Nature Catal., 2, 864-72, (2019).
2. “Bioorthogonal uncaging of cytotoxic paclitaxel through Pd nanosheet-hydrogel frameworks" A. Perez-Lopez, et al. J. Med. Chem., 63, 9650-59, (2020).
3. “Non-destructive production of exosomes loaded with ultrathin Palladium nanosheets for targeted bioorthogonal catalysis”, et al. Nature Protocols, 16, 131-63, (2021).
4. “Unveiling the interplay between homogeneous and heterogeneous catalytic mechanisms: copper-iron nanoparticles working under chemically relevant tumor conditions”, J. Bonet-Aleta, et al. Chemical Science, 13, 8307-20, (2022).
5. “In Cellulo Bioorthogonal Catalysis by Encapsulated AuPd Nanoalloys” B. Rubio-Ruiz, et al., Nano Lett. in press (2023).