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Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Dual-responsive nanoparticles loading bevacizumab and gefitinib for molecular targeted therapy against non-small cell
Zi-Tong Zhao1,2, Jue Wang2, Lei Fang2
1School of Pharmacy, Fudan University, Shanghai, 201203, China.
Abstract:
The combination of vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKIs) is newly available for molecular targeted therapy against non-small cell lung cancer (NSCLC) in clinic. However, the therapeutic benefits remain unsatisfying due to the poor drug delivery to targets of interest. In this study, we developed bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) with dual-responsive drug release for inhibiting tumor angiogenesis and phosphorylation of epidermal growth factor receptor (EGFR). Through an exogenous corona strategy, bevacizumab is easily coated on gefitinib-loaded nanoparticles via electrostatic interaction. After intravenous injection, BCGN are efficiently accumulated in NSCLC tumors as confirmed by dual-model imaging. Bevacizumab is released from BCGN upon oxidation in tumor microenvironment, whereas gefitinib is released after being internalized by tumor cells and disassembled in reduction cytoplasm. The dual-responsive release of bevacizumab and gefitinib significantly inhibits tumor growth in both A549 and HCC827 human NSCLC models. Our approach provides a promising strategy to improve combinational molecular targeted therapy of NSCLC with precisely controlled drug release.
Insights
New nanoparticles combine anti-angiogenesis and targeted therapy drugs for non-small cell lung cancer (NSCLC). This dual-drug delivery system enhances therapeutic effects by precisely releasing bevacizumab and gefitinib within tumors, improving treatment outcomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Molecular targeted therapy for non-small cell lung cancer (NSCLC) using vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKIs) shows promise.
- Current limitations in NSCLC treatment include suboptimal therapeutic benefits due to inefficient drug delivery to tumor sites.
- The combination of anti-angiogenic and anti-EGFR therapies is a key strategy for NSCLC management.
Purpose of the Study:
- To develop dual-responsive nanoparticles for combined delivery of bevacizumab and gefitinib in NSCLC.
- To investigate the efficacy of bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) in inhibiting tumor angiogenesis and EGFR phosphorylation.
- To enhance the therapeutic outcomes of NSCLC combinational molecular targeted therapy through controlled drug release.
Main Methods:
- Fabrication of bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) using an exogenous corona strategy and electrostatic interaction.
- In vivo evaluation of BCGN tumor accumulation using dual-model imaging after intravenous injection.
- Assessment of dual-responsive drug release mechanisms (oxidation for bevacizumab, reduction for gefitinib) within the tumor microenvironment and intracellularly.
- Evaluation of therapeutic efficacy by monitoring tumor growth inhibition in A549 and HCC827 human NSCLC xenograft models.
Main Results:
- BCGN demonstrated efficient accumulation in NSCLC tumors following intravenous administration.
- The nanoparticles exhibited a dual-responsive drug release profile, releasing bevacizumab in response to oxidation and gefitinib upon intracellular reduction.
- Significant inhibition of tumor growth was observed in both A549 and HCC827 NSCLC models treated with BCGN, highlighting the effectiveness of the combined therapy.
- The developed nanoparticles successfully inhibited tumor angiogenesis and EGFR phosphorylation.
Conclusions:
- The developed bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) offer a promising strategy for enhanced NSCLC combinational molecular targeted therapy.
- Dual-responsive drug release from BCGN effectively targets tumor angiogenesis and EGFR signaling pathways.
- This approach represents a significant advancement in improving drug delivery and therapeutic efficacy for non-small cell lung cancer treatment.
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