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Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
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Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

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Cascade-Targeting Apoptosis via Synergy of TRAIL-Specific Bystander Effect and Mitochondrial Photodamage in Cancer

Shengyu Liu1, Zhongsheng Ji1, Sulei Ge1

  • 1State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.

Nano Letters
|March 28, 2025
PubMed

Insights

This study introduces a novel nanoparticle system for cancer therapy, combining tumor-specific apoptosis via TRAIL expression with mitochondrial photodamage. This synergistic approach enhances cancer cell death and inhibits metastasis.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Tumor-specific apoptosis is crucial for cancer treatment, but apoptosis evasion and short TRAIL half-life limit efficacy.
  • Existing therapies face challenges with drug delivery and targeted action within cancer cells.

Purpose of the Study:

  • To develop a synergistic apoptosis strategy using orthotopic TRAIL expression and mitochondrial photodamage.
  • To enhance the bystander effect and activate intrinsic apoptosis pathways for improved cancer therapy.

Main Methods:

  • Developed cascade-targeting nanoparticles encapsulating TRAIL-expressing plasmid (pTRAIL) on graphene oxide nanosheets modified with glycyrrhetinic acid (GA).
  • Utilized GA for tumor targeting and nanoparticle dissociation for pTRAIL release and expression.
  • Engineered GA-modified graphene carriers for mitochondria distribution and laser-triggered photodamage.

Main Results:

  • Achieved 86.78% tumor inhibition in a melanoma model.
  • Demonstrated significant metastasis blocking activity.
  • Validated the synergistic apoptosis strategy through combined TRAIL bystander effects and mitochondrial photodamage.

Conclusions:

  • The developed cascade-targeting nanoparticles offer a novel oncotherapy approach by combining TRAIL-mediated bystander effects with mitochondrial photodamage.
  • This technology shows potential for enhanced cancer treatment by overcoming apoptosis evasion and improving therapeutic outcomes.
Keywords:
Bystander effectCascade-targeting deliveryMitochondrial photothermal damageOrthotopic TRAIL expressionSynergistic apoptosis effects

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