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A tyrosinase-responsive tumor-specific cascade amplification drug release system for melanoma therapy

Dongdong Li1, Xiaoxuan Zhou2, Wei Zhang1

  • 1Zhejiang Province Key Laboratory of Smart Materials, Key Laboratory of Biomass Chemical Engineering of Ministry of Education, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang, 310027, China. jianbin@zju.edu.cn.

Journal of Materials Chemistry. B
|November 8, 2021
PubMed

Insights

This study introduces novel nanoparticles that specifically target tumors, enhancing cancer treatment efficacy. The innovative design leverages tyrosinase-responsive cascade amplification for highly effective and safer melanoma therapy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Tumor heterogeneity limits current nanoparticle drug delivery efficacy.
  • Nanoparticles often reduce systemic toxicity but rarely improve clinical outcomes.
  • Melanoma treatment requires targeted approaches to enhance efficacy and minimize side effects.

Purpose of the Study:

  • To develop a tumor-specific nanoparticle system for enhanced cancer treatment.
  • To create a tyrosinase-responsive cascade amplification release nanoparticle (TR-CARN) for melanoma.
  • To improve anticancer efficacy while reducing systemic drug toxicity.

Main Methods:

  • Developed TR-CARN loaded with a ROS-responsive prodrug (BDOX) and acetaminophen (APAP).
  • Utilized tyrosinase (Tyr) expression in melanoma to catalyze APAP and increase reactive oxygen species (ROS).
  • Designed APAP linkage via a ROS-cleavable thioether bond for controlled release.

Main Results:

  • TR-CARN demonstrated reduced side effects due to the low toxicity of BDOX.
  • Endogenous ROS in tumors initiated APAP and BDOX release.
  • Tyr-mediated ROS synthesis by APAP accelerated drug release and toxification, leading to melanoma-specific treatment.

Conclusions:

  • TR-CARN offers a promising strategy for melanoma-specific cancer therapy.
  • The cascade amplification approach enhances therapeutic efficacy and biosafety.
  • This system addresses the limitations of current nanoparticle drug delivery in heterogeneous tumors.

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