Photoactivatable ruthenium compounds for more effective and selective cancer treatment

The Amido-Ruca research group has extensive expertise in inorganic and organometallic chemistry, with a strong track record in the design, synthesis, and characterization of metal complexes for biomedical applications. Its research focuses on platinum-group metal complexes, particularly those based on ruthenium (Ru), iridium (Ir), rhodium (Rh), palladium (Pd), and platinum (Pt), investigating their electrochemical, photophysical, anticancer, and catalytic properties. The group has solid expertise in structural and photophysical characterization, cyclic voltammetry, computational chemistry, and mechanistic studies, and collaborates with national and international partners to develop innovative metal-based compounds for biomedical applications.

Chemotherapy is one of the most widely used treatments against cancer; however, the chemotherapeutic agents used in clinical practice have significant limitations, primarily due to their low selectivity. A prime example is cisplatin, one of the most widely used and effective antitumor agents against various types of cancer. However, due to its mechanism of action, cisplatin not only destroys tumour cells but also affects healthy tissues with high rates of cell division, leading to significant adverse effects such as nephrotoxicity, nausea, vomiting, and alopecia. Furthermore, its reliance on platinum, a scarce and expensive metal, poses an additional limitation in terms of the treatment’s sustainability and availability.

Photodynamic therapy (PDT) has emerged as a promising alternative, as it allows for the local activation of photosensitizers (PSs) through irradiation with visible light to generate reactive oxygen species (ROS) that selectively destroy tumour cells. However, currently available PSs have significant limitations, such as tedious and inefficient synthetic processes, low efficiency in ROS generation, and poor activation by red light, whose deeper tissue penetration is essential for treating deep-seated or large tumours. These limitations have hindered the clinical adoption of PDT and highlight the need to develop new, more efficient PSs that can be activated by red light.

Applications

The technology is intended for the development of novel photodynamic therapy (PDT) protocols for the selective management of solid tumours. Activation by red light (635 nm) enables the treatment of deep-seated or large tumours due to the superior tissue penetration of this type of light. The compounds can be used as next-generation PSs for oncological applications, providing high photodynamic efficacy and remarkable selectivity toward cancer cells. The technology has been validated at the preclinical level in two-dimensional cell cultures, three-dimensional tumour spheroids, and murine models, supporting its potential for further clinical development and commercialization.

New and innovative aspects

• Development of a novel family of cyclometalated Ru(II)-based PSs with red-light absorption for PDT.
• Identification of a minimal structural modification (replacement of a hydrogen atom with a methyl group) that significantly enhances the photodynamic activity of the compound.
• Rational design combining red-light activation with efficient intracellular reactive oxygen species (ROS) generation to promote selective cancer cell destruction.
• Preclinical validation in 2D cell cultures, 3D tumour spheroids, and murine models, demonstrating the therapeutic potential of the technology.

Main advantages of its use

• High photodynamic efficacy upon red-light activation (635 nm), achieving phototoxicity indices (PI) above 9,000 and activity at nanomolar concentrations.
• Greater potential for the treatment of deep-seated solid tumours due to red-light activation, which provides superior tissue penetration compared with conventional PSs activated at shorter wavelengths.
• High therapeutic selectivity, remaining largely inactive in the absence of light while generating reactive oxygen species (ROS) only after localized irradiation, thereby minimizing damage to healthy tissues.
• Demonstrated efficacy in advanced preclinical models, including 2D cell cultures, 3D tumour spheroids, and murine models, with evidence of tumour regression following the application of a photodynamic therapy protocol.
• Favourable safety profile, including excellent blood compatibility, no significant haemolytic activity, and no detectable systemic toxicity in vivo.
• Simpler synthetic route than many state-of-the-art PSs, potentially facilitating the scaling up and future manufacturing.

Specifications

• Novel family of cyclometalated Ru(II)-based PSs for photodynamic therapy (PDT).
• Photoactivation by red-light irradiation (635 nm), enabling the treatment of tumours located in deep tissues.
• Intracellular generation of reactive oxygen species (ROS) upon irradiation as the antitumor mechanism of action.
• High photodynamic activity, with phototoxicity indices (PI) exceeding 9,000 and activity at nanomolar concentrations.
• Preclinical validation in 2D cell cultures, 3D tumour spheroids, and murine models, including pharmacokinetic, biodistribution, hemocompatibility, safety, and therapeutic efficacy studies.
• Intravenous administration, with good tolerability and rapid systemic clearance demonstrated in animal models.

Desired business relationship

Trade agreement, license agreement, technical cooperation: further development, technical cooperation: testing of new applications; technical cooperation: adaptation to specific needs.

Expected role of the partner:

- Type of partner: Pharmaceutical or biotechnology companies and medical device manufacturers active in oncology and photodynamic therapy, with capabilities in regulatory development, manufacturing scale-up, and commercialization.

- Role of the partner: The partner is expected to support further development, regulatory validation, manufacturing scaling-up and commercialization of the technology through licensing or co-development agreements, facilitating its translation into clinical applications.

Current development status

Lab tested