pH-Sensitive Shell-Core Platform Block DNA Repair Pathway To Amplify Irreversible DNA Damage of Triple Negative

Yang Dong1, Hongze Liao2, Hao Fu1

  • 1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai 200032 , China.

Insights

This study introduces a novel nanoparticle platform for treating triple-negative breast cancer (TNBC). The platform delivers BRCA1 siRNA and cisplatin to silence DNA repair and enhance chemotherapy, offering new hope for patients.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Triple-negative breast cancer (TNBC) lacks effective targeted therapies due to resistance mechanisms.
  • Developing novel drug delivery systems is crucial for improving TNBC treatment outcomes.

Purpose of the Study:

  • To develop a pH-sensitive nanoparticle platform for co-delivery of BRCA1 siRNA and cisplatin for TNBC treatment.
  • To enhance therapeutic efficacy by silencing DNA repair genes and improving chemotherapy effects.

Main Methods:

  • Encapsulation of BRCA1 siRNA and cisplatin prodrug into a pH-sensitive shell-core nanoparticle.
  • Utilizing urokinase plasminogen activator analogues (uPA) for active tumor targeting.
  • Investigating nanoparticle stability, tumor targeting, and drug release mechanisms.

Main Results:

  • The nanoparticles demonstrated high encapsulation efficiency and stability.
  • Dual passive and active targeting strategies achieved excellent tumor accumulation.
  • pH-sensitive calcium phosphate shell facilitated lysosomal escape and sequential drug release.
  • BRCA1 siRNA effectively silenced DNA repair, enhancing cisplatin's cytotoxic effect.

Conclusions:

  • The developed uPA-SP@CaP nanoparticles represent a promising strategy for effective TNBC treatment.
  • This approach offers a potential new therapeutic avenue for TNBC patients.
  • The nanoparticle system enhances chemotherapy by targeting DNA repair pathways.

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