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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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A Radioresistant-Tumor-Targeted Nanoparticle for X-Ray-Controlled Nitric Oxide Release to Potentiate Radiotherapy.

Wanze Zhang1, Xiaoyan Yin2, Ting Wang3

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Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
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Summary
This summary is machine-generated.

This study introduces a novel nanogenerator that selectively releases nitric oxide (NO) in radioresistant tumors upon irradiation. This targeted approach enhances radiotherapy efficacy by increasing DNA damage and inhibiting repair, leading to significant tumor suppression.

Keywords:
active targetingbiomaterialscontrolled releasenitric oxideradiation therapy

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Area of Science:

  • Oncology
  • Nanomedicine
  • Radiotherapy

Background:

  • Nitric oxide (NO) can overcome tumor radioresistance by reducing hypoxia and inhibiting DNA repair.
  • However, NO's systemic toxicity limits its clinical application.
  • Developing targeted NO delivery systems is crucial for cancer therapy.

Purpose of the Study:

  • To develop a tumor-selective nitric oxide (NO) nanogenerator activated by radiotherapy.
  • To enhance the efficacy of cancer treatment by overcoming radioresistance.
  • To investigate the combination therapy of radiotherapy, NO nanogenerator, and immunotherapy.

Main Methods:

  • A Glucose-Regulated Protein 78 (GRP78)-targeted nanocarrier loaded with a radiosensitive NO donor (BNN6) was synthesized (PBTN).
  • GRP78 targeting facilitated selective accumulation in radioresistant tumors.
  • Irradiation triggered BNN6 to release NO, forming peroxynitrite with reactive oxygen species to induce DNA damage and suppress repair.

Main Results:

  • PBTN selectively released NO within the irradiated tumor volume.
  • The combination of radiotherapy, PBTN, and anti-PDL1 antibody resulted in 96.5% tumor growth suppression in CT26 tumor-bearing mice.
  • An 80% survival rate was observed at 40 days post-treatment.

Conclusions:

  • The developed PBTN nanogenerator provides a safe and precise method for targeted NO delivery.
  • Irradiation-triggered NO release effectively overcomes tumor radioresistance.
  • This strategy holds promise for improving radiotherapy outcomes in combination with immunotherapy.