Abstract
In this work, three cyclometalated iridium(III) complexes modified with multiple guanidinium moieties were designed as molecular glues. Protein-binding studies showed that the complexes exhibited high binding affinity toward bovine serum albumin (BSA). One of these complexes was utilized to modify glutathione (GSH)-responsive, doxorubicin (DOX)-loaded BSA nanoparticles (DOX/SSBNPs). Notably, functionalization of DOX/SSBNPs with the complex reversed the surface charge from negative (zeta potential = – 20.2 mV) to positive (zeta potential = + 23.6 mV). Upon incubation with GSH, the size of Ir-DOX/SSBNPs decreased significantly concomitant with efficient DOX release. Additionally, the positively charged Ir-DOX/SSBNPs showed increased cellular uptake in HeLa cells, which was further shown to be important to their performance in combined chemo-photodynamic therapy. The results showed that these iridium(III)-based molecular glues can be used for intracellular drug delivery and combined chemo-photodynamic therapy.
| Original language | English |
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| Publication status | Published - 17 Mar 2025 |
| Event | LSCCB International Conference 2025 for Drug Discovery and Development - Hyatt Regency, Sha Tin, Hong Kong Duration: 17 Mar 2025 → 19 Mar 2025 https://www.lsccb-lc2025.com/ |
Conference
| Conference | LSCCB International Conference 2025 for Drug Discovery and Development |
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| Country/Territory | Hong Kong |
| City | Sha Tin |
| Period | 17/03/25 → 19/03/25 |
| Internet address |
Funding
We thank the Hong Kong Research Grants Council (Project Nos. CityU 11301121, CityU 11317022, CityU 11309423, and C7075-21GF) and the Hong Kong Research Grants Council and Natural Science Foundation of China (Project No. N-CityU104/21) for financial support. We also thank the funding support from “Laboratory for Synthetic Chemistry and Chemical Biology” under the Health@InnoHK Program Launched by Innovation and Technology Commission.