Photothermal-Driven Subcellular Calcium Ion Translocation and Mitochondrial Dysfunction for Augmented Tumor Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Photothermal therapy (PTT) offers precise cancer treatment but faces challenges like uneven heating and tumor thermotolerance due to heat shock protein 90 (HSP90).
• Overcoming these limitations requires innovative strategies to enhance PTT efficacy and target cancer cells more effectively.

Purpose of the Study:

• To develop a photothermal-driven nanoplatform (HCPH) for enhanced cancer therapy by regulating subcellular calcium ion translocation and inducing mitochondrial dysfunction.
• To investigate the synergistic effects of curcumin (CUR) and PTT mediated by HCPH for improved therapeutic outcomes.

Main Methods:

• HCPH, composed of hollow mesoporous Prussian blue nanoparticles loaded with CUR and modified with HA, was synthesized.
• The nanoplatform's photothermal conversion efficiency, targeted delivery via CD44, and CUR release under acidic conditions were evaluated.
• The study examined the combined effects of CUR-induced endoplasmic reticulum calcium release and PTT-activated TRPV1 calcium influx on cellular calcium homeostasis and mitochondrial function.

Main Results:

• HCPH demonstrated excellent photothermal conversion efficiency and targeted tumor cells.
• The synergistic action of CUR and PTT led to cytoplasmic and mitochondrial calcium overload, inducing mitochondrial dysfunction and reducing ATP synthesis.
• This calcium dysregulation further inhibited HSP90 expression, creating a positive feedback loop that enhanced PTT efficacy.
• In vitro and in vivo studies confirmed significant tumor growth inhibition and improved therapeutic outcomes with HCPH treatment.

Conclusions:

• The developed HCPH nanoplatform effectively enhances PTT by leveraging photothermal-driven subcellular calcium translocation and inducing mitochondrial damage.
• This novel approach offers a promising strategy to overcome the limitations of single-modal PTT and improve cancer treatment efficacy.