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Rose Bengal-Mediated Photodynamic Therapy to Inhibit Candida albicans
Published on: March 24, 2022
Cage-modified hypocrellin against multidrug-resistant Candida spp. with unprecedented activity in light-triggered
Xinyao Liu1, Renjie Fang2, Rui Feng3
1Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China; Academician Workstation of Wanqing Liao, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
Infections caused by multidrug-resistant fungi pose a devastating threat to human health worldwide, making new antifungal strategies urgently desired. Antimicrobial photodynamic therapy (aPDT) has gained increasing attention due to its potential in fighting against fungal infection. However, the preparation of highly efficient and water-soluble photosensitizers (PSs) for this purpose remains a challenge. Herein, we present a new strategy to prepare powerful PSs for efficient aPDT by introducing a porous cage compound, which could facilitate the transportation of O2 and reactive oxygen species (ROS). Specifically, the natural PS hypocrellin A (HA) was attached to a novel organic cage compound (covalent organic polyhedra 1 tied, COP1T) with polyethylene glycol (PEG) chains to improve its water solubility. It was found that the resulting COP1T-HA exhibited in vitro antifungal efficiency several folds higher compared to the free HA in fighting against four types of multidrug-resistant fungal planktonic cells and biofilms, including the "super fungus" Candida auris. Interestingly, the red-shift of COP1T-HA adsorption led to the realization of phototheranostic aPDT for cage-modified HA or derivatives. Additionally, COP1T-HA exhibited good biocompatibility, excellent disinfection capacity and wound healing efficiency without obvious toxic effects in vivo of rat model. With further development and optimization, COP1T-HA has great potential to become a new class of antifungal agent to fight against drug-resistant pathogens.
Insights
New porous organic cages enhance hypocrellin A for potent antimicrobial photodynamic therapy (aPDT). This strategy combats drug-resistant fungi and biofilms, offering a promising new antifungal treatment.
Area of Science:
- Biomedical Engineering
- Photochemistry
- Mycology
Background:
- Multidrug-resistant fungal infections present a critical global health challenge.
- Antimicrobial photodynamic therapy (aPDT) shows promise but is limited by photosensitizer (PS) solubility and efficiency.
- Developing effective and water-soluble PSs is crucial for advancing aPDT against fungi.
Purpose of the Study:
- To develop novel, highly efficient, and water-soluble photosensitizers for antimicrobial photodynamic therapy.
- To enhance the antifungal efficacy of hypocrellin A (HA) by conjugating it to a porous organic cage.
- To investigate the potential of cage-modified HA for treating multidrug-resistant fungal infections and biofilms.
Main Methods:
- Synthesized a novel organic cage compound (COP1T) functionalized with polyethylene glycol (PEG) chains.
- Conjugated the natural photosensitizer hypocrellin A (HA) to the COP1T-PEG structure, creating COP1T-HA.
- Evaluated the in vitro antifungal activity of COP1T-HA against multidrug-resistant fungi and biofilms, including Candida auris.
- Assessed the phototheranostic potential and in vivo biocompatibility and efficacy in a rat wound healing model.
Main Results:
- COP1T-HA demonstrated significantly higher in vitro antifungal efficiency compared to free HA against planktonic cells and biofilms.
- The modified PS effectively combated four types of multidrug-resistant fungi, including Candida auris.
- COP1T-HA exhibited a red-shifted adsorption spectrum, enabling phototheranostic applications.
- In vivo studies showed good biocompatibility, effective disinfection, and wound healing properties without significant toxicity.
Conclusions:
- The novel COP1T-HA conjugate represents a powerful photosensitizer for enhanced antimicrobial photodynamic therapy.
- This approach overcomes the limitations of traditional PSs, offering improved water solubility and antifungal efficacy.
- COP1T-HA shows significant potential as a new class of antifungal agent against drug-resistant pathogens and for wound healing applications.
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