Metallodrug targeting by conjugation and encapsulation

Published by Camilla Abbehausen

February 6, 2024

Summary

Transition metal complexes exhibit a wealth of chemical and structural versatility, providing a broad spectrum of possibilities for designing molecules with specific chemical or physicochemical effects on biological targets. Despite this potential, the therapeutic use of metallodrugs is hampered by their poor cell permeability and poor selectivity. Various strategies have been devised to overcome these limitations, with one prominent approach being the conjugation of metal complexes with different biomolecules. This versatile strategy aims to enhance the bioavailability and cellular accumulation of metallodrugs, thereby improving the site selectivity of their effects. Consequently, the conjugation of cytotoxic metal-based drugs to biomolecules holds promise for the development of bioconjugates with superior pharmacological properties and more favorable systemic toxicity profiles.

Another viable strategy for enhancing drug delivery is nanoencapsulation. Over the past decades, nanotechnology has made remarkable progress in the field of nanomedicine. The formulation of drugs into nanoparticles, termed nanomedicine, imparts a range of novel properties, including heightened bioavailability, improved pharmacokinetics, reduced toxic side effects, controlled release, and the potential for increased drug doses. This transformative approach addresses challenges associated with water-insoluble therapeutic drugs, expanding their clinical applications [1].

The creation of nanomedicines loaded with hydrophobic drugs not only improves solubility but also enhances overall drug characteristics, including stability, biodistribution, pharmacokinetics, and pharmacodynamics [2]. This strategy not only contributes to reducing drug toxicity but also reinforces therapeutic efficacy [3].

Furthermore, nanomedicines offer the flexibility to integrate additional functionalities such as imaging, triggered release, and targeted delivery, allowing for the achievement of multifunctional therapeutic outcomes [4]. This convergence of nanotechnology and medicine not only surmounts existing limitations but also paves the way for the development of advanced and versatile drug delivery systems with diverse applications in healthcare.

Our research group is actively engaged in the development of both strategies to improve the bioavailability and selectivity of metallodrugs. To this end, we are working on synthetic strategies, encapsulation methodologies, evaluating the biological outcomes of these approaches and chemically characterizing their properties.

Research Outcomes

(1) Teles, C. M.; Antunes, V. U.; Cardoso, R. S.; Candido, T. Z.; Lima, C. S. P.; Ruiz, A. L. T. G.; Juliano, M. A.; Favaro, D. C.; Abbehausen, C. Functionalization of New Anticancer Pt(II) Complex with Transferrin Receptor Binding Peptide. Inorganica Chimica Acta 2020, 511, 119811. https://doi.org/10.1016/j.ica.2020.119811.

(2) Teles, C. M.; Lammoglia, L. C.; Juliano, M. A.; Ruiz, A. L. T. G.; Candido, T. Z.; de Carvalho, J. E.; Lima, C. S. P.; Abbehausen, C. Novel Anticancer PdII Complexes: The Effect of the Conjugation of Transferrin Binding Peptide and the Nature of Halogen Coordinated on Antitumor Activity. Journal of Inorganic Biochemistry 2019, 199, 110754. https://doi.org/10.1016/j.jinorgbio.2019.110754.

(3) Martins, P.; Machado, D.; Theizen, T. H.; Guarnieri, J. P. O.; Bernardes, B. G.; Gomide, G. P.; Corat, M. A. F.; Abbehausen, C.; Módena, J. L. P.; Melo, C. F. O. R.; Morishita, K. N.; Catharino, R. R.; Arns, C. W.; Lancellotti, M. Outer Membrane Vesicles from Neisseria Meningitidis (Proteossome) Used for Nanostructured Zika Virus Vaccine Production. Sci Rep 2018, 8 (1), 8290. https://doi.org/10.1038/s41598-018-26508-z.

(4) Galuppo, C.; Alvarenga, J.; Queiroz, A. C.; Messias, I.; Nagao, R.; Abbehausen, C. The Electrosynthesis of Gold(I) Complexes: A Clean, One-Pot Method. Electrochem Comm 2020, 110, 106620. https://doi.org/10.1016/j.elecom.2019.106620.

(5) Candido, T. Z.; de Paiva, R. E. F.; Figueiredo, M. C.; de Oliveira Coser, L.; Frajácomo, S. C. L.; Abbehausen, C.; Cardinalli, I. A.; Lustri, W. R.; Carvalho, J. E.; Ruiz, A. L. T. G.; Corbi, P. P.; Lima, C. S. P. Silver Nimesulide Complex in Bacterial Cellulose Membranes as an Innovative Therapeutic Method for Topical Treatment of Skin Squamous Cell Carcinoma. Pharmaceutics 2022, 14 (2), 462. https://doi.org/10.3390/pharmaceutics14020462.

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