A cathelicidin antimicrobial peptide delivered via dissolving microneedles combined with photodynamic therapy reduced deep skin Candida biofilm infections by 94% in animal models.
~94% fungal reductionCathelicidin peptide in dissolving microneedles combined with NIR-activated photodynamic therapy eliminated biofilm-embedded Candida in deep skin infection models
What the researchers found
The novel cathelicidin peptide HcCATH-KL30 (CATH) showed potent antifungal activity against free-floating C. albicans but was ineffective against biofilm-embedded fungi. To overcome this limitation:
- CATH was loaded into bilayer dissolving microneedles (DMNs) with indocyanine green (ICG) for photodynamic therapy
- Near-infrared irradiation generated reactive oxygen species that disrupted the biofilm matrix
- With the biofilm broken, CATH penetrated to kill the fungal cells
- In vitro, ex vivo, and in vivo results showed ~94% reduction in fungal burden
- Mechanism confirmed by qRT-PCR and propidium iodide staining
This is the first time this antimicrobial peptide has been explored through a drug delivery platform.
Why it matters
Biofilm-associated fungal infections cause serious illness, particularly in immunocompromised patients, and resist standard antifungal drugs. This dual approach — using microneedles to deliver peptides past the skin barrier and light therapy to destroy biofilm armor — tackles the two biggest obstacles to treating these infections simultaneously.
How the study worked
The cathelicidin peptide was loaded into bilayer dissolving microneedle patches containing indocyanine green as a photosensitizer. Efficacy was tested in vitro against planktonic and biofilm C. albicans, ex vivo on skin models, and in vivo in mouse models of deep dermal candidiasis. NIR irradiation was applied to activate photodynamic therapy. Mechanisms were validated through qRT-PCR gene expression analysis and propidium iodide staining for cell death.
What this study cannot tell us
This is a preclinical study tested only in mouse models. The specific light exposure requirements (NIR equipment) may limit clinical practicality. Long-term safety of microneedle-delivered peptides and repeated PDT exposure in human skin was not assessed. The approach was tested against only one fungal species (C. albicans).
How to read the evidence
Preclinical study with comprehensive validation across in vitro, ex vivo, and in vivo models with mechanistic confirmation. Strong for proof of concept, but requires clinical validation in human patients.
When this study was published
Published in 2025, this represents cutting-edge work at the intersection of antimicrobial peptides, microneedle technology, and photodynamic therapy.
The bigger picture
This study exemplifies the convergence of antimicrobial peptide research, nanotechnology (microneedles), and photomedicine. As drug-resistant fungal infections become a growing global health threat, innovative delivery systems that combine multiple mechanisms of action may provide the breakthrough needed to treat infections that current drugs cannot reach.
Questions still open
- Could this microneedle-PDT approach be effective against other biofilm-forming fungi and bacteria?
- Is the NIR light exposure practical and tolerable for clinical use in patients?
- How does the cost and complexity of this system compare to conventional antifungal treatments?
Common questions
Why can't regular antifungal drugs treat deep skin fungal infections?
How do dissolving microneedles work?
Read the original research
Breaking Biofilm Barriers: Using CATH-ICG-Loaded Bilayer Dissolving Microneedle-Assisted Photodynamic Therapy for Deep Skin Candidiasis.
Molecular pharmaceutics, 22(7), 4101-4124
Citation
Hussain, Yaseen; Dormocara, Amos; Li, Huifang; Li, Chengguo; Khan, Muhammad Kamran; Ma, Yonghao; Leng, Gang; Wang, Yipeng; You, Ben-Gang; Cui, Jing-Hao. (2025). Breaking Biofilm Barriers: Using CATH-ICG-Loaded Bilayer Dissolving Microneedle-Assisted Photodynamic Therapy for Deep Skin Candidiasis.. Molecular pharmaceutics, 22(7), 4101-4124. https://doi.org/10.1021/acs.molpharmaceut.5c00367