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

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This study introduces a novel nanoplatform (HCPH) that enhances photothermal therapy (PTT) by regulating calcium ions and mitochondrial function. HCPH improves cancer treatment by overcoming PTT limitations and boosting therapeutic efficacy.

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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.