Tumor microenvironment (TME)-activatable circular aptamer-PEG as an effective hierarchical-targeting molecular...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Photodynamic therapy (PDT) utilizes light-activated agents to generate reactive oxygen species (ROS) for cancer cell destruction.
• Effective in vivo delivery of PDT agents is hindered by biological barriers like the tumor microenvironment (TME) and extracellular matrix (ECM).
• Designing smart drug delivery systems requires balancing diverse functional requirements throughout the delivery process.

Purpose of the Study:

• To develop TME-activatable nanostructures for efficient in vivo cancer imaging and PDT.
• To overcome challenges in drug delivery for improved therapeutic outcomes.
• To create a system combining PEGylation for circulation and aptamers for cancer cell targeting.

Main Methods:

• Fabrication of pyrochlorophyll A (PA)-aptamer-PEG (PA-Apt-CHO-PEG) nanostructures.
• Evaluation of "stealth-like" properties for prolonged blood circulation post-intravenous injection.
• Assessment of TME-triggered structural changes and in situ formation of aptamer-drug conjugations (ApDCs) within solid tumors.

Main Results:

• PA-Apt-CHO-PEG nanostructures exhibited prolonged circulation, evading premature clearance.
• In the TME, nanostructures were cleaved, forming PA-Apt ApDCs that facilitated deep tumor penetration.
• The developed ApDCs demonstrated specific recognition and targeting of cancer cells.

Conclusions:

• TME-activatable PA-Apt-CHO-PEG nanostructures offer a promising strategy for enhanced in vivo imaging and PDT.
• The dual functionality of stealth circulation and targeted delivery addresses key challenges in cancer nanomedicine.
• This approach holds potential for future clinical translation in cancer therapy.