The enhanced photothermal therapy against gastric cancer by mitochondria/STAT3-targeted nanoplatform with OXPHOS...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Near-infrared (NIR) photothermal therapy (PTT) shows promise for gastric cancer (GC) ablation.
• Challenges include heat shock protein upregulation, abnormal tumor vascularization, and poor drug specificity, limiting PTT efficacy.
• Developing targeted strategies is crucial to overcome these limitations in GC treatment.

Purpose of the Study:

• To design and evaluate a novel mitochondria/STAT3-targeted nanoplatform (ATO/CR NPs) for enhanced GC therapy.
• To investigate the synergistic effects of atorvaquinone (ATO) and NIR phototherapeutic agent CR within the nanoplatform.
• To assess the nanoplatform's potential to overcome limitations of traditional PTT in GC.

Main Methods:

• Self-assembly of FDA-approved atorvaquinone (ATO) and NIR agent CR into nanoparticles (ATO/CR NPs).
• Evaluation of enhanced PTT efficiency through oxidative phosphorylation (OXPHOS) blocking in mitochondria.
• Assessment of STAT3 targeting by ATO to inhibit proliferation, angiogenesis, and promote apoptosis in GC cells.

Main Results:

• ATO/CR NPs demonstrated enhanced PTT efficiency by downregulating ATP and HSP via mitochondrial OXPHOS inhibition.
• ATO specifically targeted STAT3 in GC cells, leading to reduced proliferation, inhibited angiogenesis, and induced apoptosis.
• The multimodal nanoplatform achieved accurate cancer cell targeting and amplified photo-ablation activity.

Conclusions:

• The developed mitochondria/STAT3-targeted nanoplatform (ATO/CR NPs) offers a promising multimodal strategy for GC treatment.
• This approach effectively enhances PTT by inducing mitochondrial dysfunction and apoptosis, overcoming key therapeutic hurdles.
• Further preclinical investigation is warranted to explore the full therapeutic potential of ATO/CR NPs for gastric cancer.