Bi-A@SR Nanoparticles Enable Tumor-Localized NO Release to Suppress HSP70 and Reverse Chemoresistance

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Cervical cancer (CC) treatment faces challenges like chemoresistance and poor drug delivery.
• Heat shock protein 70 (HSP70) is a key factor in resistance to chemotherapy and photothermal therapy in CC.
• Current CC therapies lack real-time monitoring and effective strategies to overcome resistance mechanisms.

Purpose of the Study:

• To develop a novel theranostic nanoplatform for improved cervical cancer treatment.
• To overcome chemoresistance and enhance therapeutic outcomes by targeting HSP70.
• To integrate imaging capabilities for guided delivery and therapy monitoring.

Main Methods:

• Developed bismuth selenide nanoparticles (Bi2Se3) co-loaded with SN38 (chemotherapy drug) and IR820 (photosensitizer).
• Decorated nanoparticles with cyclic RGD (cRGD) for tumor targeting and nitric oxide (NO) generation.
• Utilized computed tomography (CT) and near-infrared fluorescence imaging (NIRF) for tracking and guidance.
• Investigated the combined effects of photothermal therapy, photodynamic therapy, and NO release triggered by 808 nm irradiation.

Main Results:

• The nanoplatform demonstrated effective tumor targeting and drug accumulation.
• NIR irradiation induced hyperthermia and reactive oxygen species (ROS), triggering on-demand NO release.
• NO generation suppressed therapy-induced HSP70 upregulation, overcoming stress adaptation.
• The integrated chemo-phototherapy approach significantly enhanced treatment efficacy in cervical cancer models.

Conclusions:

• The developed Bi2Se3-based nanotheranostic platform offers a promising strategy for cervical cancer treatment.
• Combining imaging-guided delivery, on-demand NO sensitization, and HSP70 inhibition enhances therapeutic outcomes.
• This approach provides a coordinated method to address chemoresistance and improve patient treatment in cervical cancer.