Zn-Based Multi-Active Framework Nanoparticles TSA-CAN-Zn Inhibit Skin Glycation via Dual Blockade of HMGB1/RAGE and

Cheng Yao1,2, Heqi Wang3, Jingxia Han3

  • 1Cheermore Cosmetic Dermatology Laboratory, Shanghai, China.

PubMed

Insights

This study introduces TSA-CAN-Zn nanoparticles to combat skin damage from advanced glycation end products (AGEs). These nanoparticles inhibit key pathways, reducing inflammation and AGEs accumulation for healthier skin.

Area of Science:

  • Biochemistry
  • Dermatology
  • Nanotechnology

Background:

  • Receptor for advanced glycation end products (RAGE) is crucial in skin damage caused by glycation.
  • High-mobility group 1B protein (HMGB1) and advanced glycation end products (AGEs) are primary RAGE ligands.
  • Simultaneously blocking HMGB1/RAGE and AGEs/RAGE pathways offers a strategy to reduce glycation-induced skin damage.

Purpose of the Study:

  • To design and evaluate Zn-based nanoparticles (TSA-CAN-Zn) for simultaneous inhibition of HMGB1/RAGE and AGEs/RAGE pathways.
  • To investigate the therapeutic potential of TSA-CAN-Zn in mitigating glycation-induced skin damage.
  • To elucidate the molecular mechanisms underlying TSA-CAN-Zn's effects on skin cells and pathways.

Main Methods:

  • Molecular docking identified Theasinensin A (TSA) as an inhibitor of HMGB1-RAGE interaction.
  • TSA-CAN-Zn nanoparticles were synthesized, incorporating TSA and L-carnosine (CAN).
  • In vitro assays (HaCaT cells, mouse skin models) and single-cell RNA sequencing were employed to assess efficacy and mechanisms.

Main Results:

  • TSA-CAN-Zn exhibited radical scavenging and AGEs formation inhibition.
  • The nanoparticles reduced glycation-induced ROS, apoptosis, and inflammation in HaCaT cells.
  • TSA-CAN-Zn enhanced lysosomal AGEs degradation and improved skin damage in a mouse model, primarily affecting RAGE downstream pathways.

Conclusions:

  • TSA-CAN-Zn nanoparticles effectively inhibit both HMGB1/RAGE and AGEs/RAGE pathways.
  • These nanoparticles demonstrate therapeutic potential for ameliorating glycation-induced skin damage.
  • TSA-CAN-Zn represents a promising candidate for treating skin aging and glycation-related conditions.

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