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Theranostics 2020; 10(11):4795-4808. doi:10.7150/thno.42922 This issue Cite

Research Paper

pH responsive superporogen combined with PDT based on poly Ce6 ionic liquid grafted on SiO₂ for combating MRSA biofilm infection

Chaoli Wang^1*, Peng Chen^1*, Youbei Qiao^1*, Yuan Kang², Chaoren Yan², Zhe Yu¹, Jian Wang³, Xin He¹, Hong Wu^1✉

1. Department of pharmacy, Air Force Medical University, Xi'an, 710032, Shaanxi Province, China
2. Department of physics, Northwest University of Technology, Xi'an, 710032, Shaanxi Province, China
3. Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi Province, China
*These authors contributed equally to this work

✉ Corresponding author: Hong Wu (wuhongedu.cn). Department 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-P_Ce6-IL) was developed. Because of the protonation of the photosensitizer and the high binding energy of the polyionic liquid, SiO₂-P_Ce6-IL changed to positive SiO₂-P_IL⁺ in an acidic microenvironment of biofilm infection. SiO₂-P_IL⁺ could combine with negatively charged extracellular polymeric substances (EPS) and create holes to remove the biofilm barrier. To strengthen the interaction between SiO₂-P_IL⁺ and EPS, SiO₂-P_IL⁺ 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-P_IL⁺ with EPS, SiO₂-P_Ce6-IL could release 90% of Ce6 in 10 s. With the stronger electrostatic and hydrophobic interaction of SiO₂-P_IL⁺ 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-P_Ce6-IL dramatically improved the PDT efficacy against MRSA biofilm infection.

Conclusion: These findings suggest that SiO₂-P_Ce6-IL could rapidly increase the concentration of photosensitizer in biofilm and it is an effective therapy for combating biofilm infection.

Keywords: pH-responsive, polyionic liquids, superporogen, photosensitizer, SiO₂, MRSA biofilm

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