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Nitric Oxide-Releasing Topical Treatments for Cutaneous Melanoma

Quincy E Grayton1, Heba El-Ahmad2, Anna L Lynch1

  • 1Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.

Molecular Pharmaceutics
|October 1, 2024
PubMed

Insights

Nitric oxide (NO) donors show promise for melanoma treatment, with efficacy depending on NO payload. Macromolecular NO donors offer targeted delivery and reduced toxicity to healthy cells, improving therapeutic potential.

Area of Science:

  • Biochemistry
  • Materials Science
  • Dermatology

Background:

  • Melanoma exhibits high drug resistance and current treatments like immunotherapy cause adverse effects.
  • Nitric oxide (NO) possesses anticancer properties, low resistance potential, and limited toxicity, making it a potential melanoma therapeutic.
  • Understanding NO donor characteristics is crucial for optimizing antimelanoma activity.

Purpose of the Study:

  • To evaluate the in vitro therapeutic efficacy of three macromolecular nitric oxide (NO) donor systems.
  • To assess skin permeation and toxicity of NO donors against melanoma and healthy skin cells.
  • To optimize a delivery system for enhanced NO donor performance.

Main Methods:

  • Investigated three macromolecular NO donor systems: cyclodextrin, mesoporous silica nanoparticles, and hyaluronic acid.
  • Assessed in vitro cytotoxicity against melanoma and healthy skin cells.
  • Evaluated in vitro skin permeation based on NO donor size and charge.
  • Optimized a Pluronic F127 organogel for NO donor delivery.

Main Results:

  • Melanoma cell cytotoxicity correlated with NO payload, irrespective of donor type or release kinetics.
  • Healthy cell cytotoxicity varied by donor; cyclodextrin and hyaluronic acid donors showed higher therapeutic indices.
  • Smaller, neutral NO donors exhibited greater skin permeation.
  • Organogel delivery of a cyclodextrin-based NO donor enhanced skin permeation and reduced tumor growth in vivo.

Conclusions:

  • Macromolecular NO donors can be tailored for melanoma treatment, balancing efficacy and safety.
  • NO donor properties (size, charge, payload) significantly influence therapeutic outcomes and delivery.
  • Optimized delivery systems, like organogels, can improve the clinical potential of NO-based melanoma therapies.
Keywords:
cyclodextrinhyaluronic acidmelanomamesoporous silica nanoparticlesnitric oxidetopical delivery

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