Electrostatic Force-Enabled Microneedle Patches that Exploit Photoredox Catalysis for Transdermal Phototherapy

Area of Science:

• Biomedical Engineering
• Photodynamic Therapy
• Drug Delivery Systems

Background:

• Microneedle patches offer a safe and noninvasive method for topical administration of photodynamic therapy (PDT) sensitizers.
• Challenges include inefficient photosensitizer delivery and the immunosuppressive, hypoxic tumor microenvironment.
• Developing novel strategies to enhance photosensitizer efficacy and overcome tumor microenvironment limitations is crucial.

Purpose of the Study:

• To develop an advanced microneedle patch for enhanced topical delivery of a photosensitizer, zinc-containing porphyrin analogue (ZnBP(w)).
• To investigate the role of intermolecular electrostatic interactions in improving photosensitizer loading and facilitating photoinduced electron transfer.
• To evaluate the antiangiogenic and antitumor efficacy of the developed microneedle patch in preclinical models.

Main Methods:

• Fabrication of microneedle patches incorporating ZnBP(w) utilizing intermolecular electrostatic interactions.
• Assessment of mechanical strength and photosensitizer loading efficiency in aqueous environments.
• Investigation of photoinduced electron transfer between ZnBP(w) and NADH upon photoirradiation.
• Evaluation of antiangiogenesis in a vascular malformation model and antitumor activity in a melanoma mouse model following transdermal administration.

Main Results:

• The microneedle patch design enhanced mechanical strength and photosensitizer loading efficiency.
• Efficient electron transfer between ZnBP(w) and NADH was observed upon photoirradiation, driven by electrostatic interactions.
• Disruption of NADH/NAD+ homeostasis was induced, leading to tumor cell death.
• The microneedle patch demonstrated significant antiangiogenesis and antitumor effects in vivo.
• Reduced systemic phototoxicity was observed compared to conventional methods.

Conclusions:

• Electrostatic interactions are beneficial for designing effective microneedle PDT patches.
• The developed microneedle patch enhances photosensitizer delivery and efficacy by exploiting electron transfer mechanisms.
• This approach shows significant potential for clinical application in cancer therapy, offering improved outcomes and reduced side effects.