Tumor targeting and microenvironment-responsive nanoparticles for gene delivery.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Tumor microenvironment is characterized by low extracellular pH (pHe) and elevated matrix metalloproteinase 2 (MMP2).
• Targeted delivery of therapeutic agents to tumors remains a challenge in cancer treatment.

Purpose of the Study:

• To develop a dual-responsive nanoparticle system for enhanced tumor targeting and gene delivery.
• To engineer an activatable cell-penetrating peptide (dtACPP) for triggered nanoparticle internalization.

Main Methods:

• Nanoparticles modified with dtACPP, which is masked and activated by low pHe and MMP2.
• Evaluation of nanoparticle properties including plasmid DNA loading, toxicity, cellular uptake, and tumor targeting.
• Assessment of gene transfection efficiency in vitro and in vivo.

Main Results:

• The dtACPP modification enables nanoparticles to accumulate in tumors via the enhanced permeability and retention (EPR) effect.
• Low pHe and MMP2 in the tumor microenvironment activate dtACPP, exposing the cell-penetrating peptide (CPP).
• Activated CPP drives efficient nanoparticle internalization into intratumoral cells, facilitating gene delivery.

Conclusions:

• The dtACPP-modified nanoparticle system demonstrates effective tumor targeting and enhanced gene delivery.
• This dual-responsive system holds significant potential for advanced cancer gene therapy applications.