Tumor Microenvironment-Triggered Charge-Reversible Molecularly Imprinted Polymers for Dual Cascade Targeting to...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapy

Background:

• Mitochondria are crucial for cellular energy and metabolism, making them ideal targets for photothermal therapy (PTT).
• Existing mitochondrial targeting agents face challenges like rapid clearance and off-target effects on normal cells.
• Developing effective and specific mitochondrial targeting strategies is essential for improving PTT outcomes.

Purpose of the Study:

• To design and synthesize a novel cascade-targeting molecularly imprinted polymer (MIP) with charge-reversal capabilities for enhanced PTT.
• To overcome limitations of current mitochondrial targeting agents, such as poor circulation stability and non-specific targeting.
• To improve tumor targeting specificity, cellular internalization, and overall anti-tumor efficacy of PTT.

Main Methods:

• Synthesized a charge-reversal MIP using Fe3O4 nanoparticles modified with (3-carboxypropyl)triphenylphosphonium bromide for photothermal effect and initial targeting.
• Incorporated 2-methacryloyloxyethyl phosphorylcholine to enhance imprinting and introduce charge-reversal properties for improved tumor targeting.
• Utilized glutathione-mediated degradation for secondary mitochondrial targeting after intracellular entry and 808 nm laser irradiation for photothermal effect.

Main Results:

• The synthesized MIP demonstrated effective cascade targeting, confirmed by cellular uptake and mitochondrial colocalization studies.
• Charge-reversal capability facilitated enhanced internalization in tumor spheroids, indicating improved penetration and targeting.
• In vivo experiments showed significant anti-tumor efficacy of the MIP under laser irradiation, outperforming conventional approaches.

Conclusions:

• The developed MIP successfully integrates charge reversal and cascade targeting for improved mitochondrial delivery and PTT.
• This novel strategy offers enhanced specificity, cellular internalization, and therapeutic efficacy for tumor photothermal therapy.
• The designability of MIPs provides a versatile platform for developing advanced therapeutic agents for cancer treatment.