A "Detachable Polyanionic Protective Shell" Enveloping Photodynamic Cationic Nanoassemblies for Keratitis Treatment

Area of Science:

• Biomaterials Science
• Nanotechnology
• Ophthalmology

Background:

• Bacterial keratitis requires new antibacterial therapies due to rapid progression.
• Cationic polymers show promise but have cytotoxicity issues.
• A strategy is needed to improve cationic polymer safety and targeted delivery.

Purpose of the Study:

• To develop a "detachable polyanionic protective shell (DPPS)" strategy for cationic polymers.
• To create a functional nano-assembly (PQCT) with adaptable charge properties.
• To evaluate PQCT's efficacy and safety in treating bacterial keratitis.

Main Methods:

• Co-assembly of quaternary ammonium salt (QAS)-modified polylysine and chlorin e6 (Ce6) into nanoassemblies (PQC).
• Encapsulation of PQC with polythioctic acid (PTA) to form the DPPS, yielding PQCT.
• In vitro and in vivo studies to assess antibacterial activity and biocompatibility post-laser irradiation.

Main Results:

• PQCT exhibits a net negative charge under physiological conditions, ensuring good biocompatibility.
• Laser irradiation triggers ROS production, leading to DPPS degradation and charge reversal to positive.
• Exposed QAS and ROS demonstrate potent antibacterial effects, validated in vitro and in vivo.
• PQCT showed outstanding performance in treating bacterial keratitis models.

Conclusions:

• The DPPS strategy effectively shields cationic polymer charges, reducing cytotoxicity.
• PQCT demonstrates targeted, laser-activated antibacterial activity with enhanced safety.
• This approach offers a promising therapeutic strategy for bacterial infections, especially bacterial keratitis.