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Novel prodrug for tumour treatment with minimized side effects

Scientists at Leiden University are developing new ruthenium-based photoactivatable prodrugs, which can be converted upon visible light irradiation into species active against cancer cells.

Like in photodynamic therapy, such prodrugs can be used as poorly toxic antitumour treatments capable of stopping tumour growth or inducing tumour regression when light is irradiated on the tumour, which will ultimately minimize side effects for cancer patients.

Due to their antitumour properties metal-based drugs such as cisplatin are commercially available as chemotherapeutic agents. Although they are very efficient for example against testicular or ovarian cancers, these metallodrugs induce severe side effects for cancer patients, such as kidney damages. In addition, acquired resistance is not uncommon. To overcome these drawbacks new anticancer agents based on ruthenium have been developed with excellent antitumour properties. However, general toxicity towards the organism remains an issue. In addition, their pharmaceutical applications are often limited by poor water solubility.

To obviate these disadvantages, scientists at Leiden University have developed a concept allowing for transforming a water-insoluble ruthenium anticancer compound that shows good cytotoxicity in the dark, into water-soluble, photoactivatable ruthenium-based prodrugs, which are much less toxic in the dark, but can be selectively converted into an antitumor-active form upon visible light irradiation. Like in photodynamic therapy (PDT), the tumouricidal effect of the prodrug is limited at the irradiation site, thus minimizing side effects for the cancer patient. However, the mechanism of action is completely different than in PDT, which should make this new strategy eligible also in case of PDT-resistant tumours. Visible or near infrared light can be employed, which will minimize damages on living tissues.

Key benefits

  • Potential activity against photodynamic-resistant tumours and cisplatin-resistant tumours
  • Tumour irradiation with light enhances the local effectiveness of the drug while it minimizes side effects for the patient
  • The prodrugs are soluble in water, allowing easier pharmaceutical preparation and different pharmacokinetics and pharmacodynamics, compared to conventional ruthenium drugs
  • No premature release of the toxic/active species in the dark
  • No UV light needed; irradiation-induced damages on living tissues are minimized

Applications

Anti-tumour photochemotherapy

Development stage

  • Proof-of-concept of prodrug activation upon visible light irradiation
  • Attachment of ruthenium prodrugs on liposomes for combination with cancer cell-targeting tools

Luris reference number

INV-074.092

Patent status

A patent application has been filed

Data available on request

Patent texts