Folic Acid-functionalized Liposomal Covalent Organic Framework for Enhanced Photothermal Cancer Therapy

Area of Science:

• Nanotechnology
• Biomedical Engineering
• Materials Science

Background:

• Indocyanine Green (ICG) exhibits poor photostability and rapid clearance, limiting its efficacy in photothermal therapy (PTT).
• Conventional PTT faces challenges in targeted drug delivery and controlled release, impacting treatment precision and outcomes.

Purpose of the Study:

• To construct a novel folic acid (FA)-modified, pH/Near-Infrared (NIR) responsive Covalent Organic Framework (COF) nanodelivery system.
• To enhance targeted delivery of ICG and achieve precise, controlled release for improved PTT efficacy.
• To overcome the limitations of ICG's poor photostability and rapid clearance in PTT.

Main Methods:

• FA-Lip-IC nanoparticles were synthesized via solvent evaporation.
• Morphology and size were characterized using Transmission Electron Microscopy (TEM) and dynamic light scattering.
• Drug release kinetics were assessed under varying pH conditions and NIR irradiation.
• Cellular uptake was analyzed via Confocal Laser Scanning Microscopy (CLSM) and flow cytometry.
• Biocompatibility was evaluated using MTT assays, hemolysis tests, and a zebrafish model.
• Pharmacokinetics were monitored in rats via blood fluorescence intensity.

Main Results:

• FA-Lip-IC nanoparticles exhibited uniform spherical morphology (577.4 ± 9.42 nm).
• High cumulative drug release (92.56 ± 0.81%) was achieved at pH 5.5 with NIR irradiation.
• FA modification significantly enhanced cellular uptake in ID8 and 4T1 cells.
• FA-Lip-IC demonstrated a significant temperature increase (>20°C) under 808 nm laser irradiation, leading to enhanced cytotoxicity compared to free ICG.
• The system showed excellent biocompatibility with low hemolysis (<3%), high normal cell viability (>87%), and prolonged blood circulation time.

Conclusions:

• The developed COF-based nanodelivery platform integrates high loading capacity with liposome biocompatibility.
• FA targeting and stimuli-responsive (pH/NIR) release enhance treatment precision for PTT.
• This FA-Lip-IC system offers a promising strategy to improve PTT efficacy and advance precision cancer therapy, despite the current lack of in vivo efficacy data.