Nucleolin-targeted silicon-based nanoparticles for enhanced chemo-sonodynamic therapy of diffuse large B-cell...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Traditional chemotherapy for diffuse large B-cell lymphoma (DLBCL) suffers from poor selectivity and high systemic toxicity.
• Sonodynamic therapy (SDT) combined with chemotherapy offers a promising strategy to enhance cancer treatment outcomes and minimize side effects.
• Challenges in SDT include rapid drug clearance and lack of targeting specificity.

Purpose of the Study:

• To develop a biocompatible nanomedicine delivery system for targeted DLBCL treatment.
• To integrate chemotherapy (doxorubicin) and sonosensitizer (indocyanine green) into a single nanoplatform.
• To enhance targeted delivery and therapeutic efficacy while ensuring biosafety.

Main Methods:

• Development of a nanomedicine (PA-HM@DOX/ICG) using hollow mesoporous silica nanoparticles (HMSNs) loaded with doxorubicin (DOX) and indocyanine green (ICG).
• Surface modification with DSPE-PEG-AS1411 for active targeted delivery via nucleolin recognition.
• In vitro studies using SU-DHL-4 lymphoma cells and LO2 normal hepatocytes.
• In vivo studies in tumor-bearing mice.

Main Results:

• PA-HM@DOX/ICG demonstrated specific uptake by nucleolin-overexpressing SU-DHL-4 cells.
• Synergistic effects of DOX and ultrasound-activated ICG induced apoptosis in cancer cells.
• The nanomedicine showed minimal toxicity to normal hepatocytes.
• In vivo studies confirmed tumor accumulation via EPR effect and active targeting, leading to significant tumor growth inhibition under ultrasound irradiation.

Conclusions:

• The developed nanoplatform effectively integrates chemotherapy and SDT for DLBCL treatment.
• PA-HM@DOX/ICG offers a targeted and efficient therapeutic approach with improved biosafety.
• This nanomedicine represents a novel strategy for overcoming limitations of conventional DLBCL therapies.