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pH responsive superporogen combined with PDT based on poly Ce6 ionic liquid grafted on SiO2 for combating MRSA
Chaoli Wang1, Peng Chen1, Youbei Qiao1
1Department of pharmacy, Air Force Medical University, Xi'an, 710032, Shaanxi Province, China.
Abstract:
Background: Biofilm infection caused by multidrug-resistant bacteria is difficult to eradicate by conventional therapies. Photodynamic therapy (PDT) is an effective antibacterial method for fighting against biofilm infection. However, the blocked photosensitizers outside of biofilm greatly limit the efficacy of PDT. Methods: Herein, a novel acid-responsive superporogen and photosensitizer (SiO2-PCe6-IL) was developed. Because of the protonation of the photosensitizer and the high binding energy of the polyionic liquid, SiO2-PCe6-IL changed to positive SiO2-PIL+ in an acidic microenvironment of biofilm infection. SiO2-PIL+ could combine with negatively charged extracellular polymeric substances (EPS) and create holes to remove the biofilm barrier. To strengthen the interaction between SiO2-PIL+ and EPS, SiO2-PIL+ of high charge density was prepared by grafting the high-density initiation site of ATRP onto the surface of the SiO2 base. Results: Due to the rapid protonation rate of COO- and the strong binding energy of SiO2-PIL+ with EPS, SiO2-PCe6-IL could release 90% of Ce6 in 10 s. With the stronger electrostatic and hydrophobic interaction of SiO2-PIL+ with EPS, the surface potential, hydrophobicity, adhesion and mechanical strength of biofilm were changed, and holes in the biofilm were created in 10 min. Combining with the release of photosensitizers and the porous structure of the biofilm, Ce6 was efficiently concentrated in the biofilm. The in vitro and in vivo antibacterial experiments proved that SiO2-PCe6-IL dramatically improved the PDT efficacy against MRSA biofilm infection. Conclusion: These findings suggest that SiO2-PCe6-IL could rapidly increase the concentration of photosensitizer in biofilm and it is an effective therapy for combating biofilm infection.
Insights
This study introduces a novel photosensitizer that effectively penetrates biofilms, enhancing photodynamic therapy (PDT) efficacy against multidrug-resistant bacteria. The developed material creates pores in biofilms, improving PDT treatment outcomes.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Antimicrobial Therapy
Background:
- Biofilm infections from multidrug-resistant bacteria are challenging to treat with conventional methods.
- Photodynamic therapy (PDT) shows promise but is limited by photosensitizer penetration into biofilms.
- Existing treatments struggle to overcome the physical barrier posed by biofilm extracellular polymeric substances (EPS).
Purpose of the Study:
- To develop an acid-responsive superporogen and photosensitizer (SiO2-P-Ce6-IL) for enhanced biofilm eradication.
- To improve the penetration and efficacy of photosensitizers within bacterial biofilms.
- To create a novel therapeutic strategy for combating multidrug-resistant bacterial biofilm infections.
Main Methods:
- Fabrication of an acid-responsive silica-based material (SiO2-P-Ce6-IL) incorporating a photosensitizer (Ce6) and a polyionic liquid.
- Modification of the material to create a high charge density (SiO2-P-IL+) for strong interaction with negatively charged EPS in biofilms.
- Utilizing the acid-responsive nature of the material to generate pores within the biofilm structure, facilitating photosensitizer release and concentration.
Main Results:
- The developed SiO2-P-Ce6-IL rapidly releases the photosensitizer (Ce6) upon encountering the acidic biofilm microenvironment.
- The material effectively disrupts the biofilm matrix by altering its surface potential, hydrophobicity, and mechanical strength, creating pores.
- Enhanced accumulation of Ce6 within the biofilm and significantly improved in vitro and in vivo PDT efficacy against MRSA biofilms were observed.
Conclusions:
- SiO2-P-Ce6-IL demonstrates rapid photosensitizer concentration within biofilms.
- This novel material offers a highly effective therapeutic approach for combating challenging biofilm infections.
- The findings highlight the potential of acid-responsive nanomaterials in enhancing antimicrobial photodynamic therapy.
