The relief of hypoxic microenvironment using an O2 self-sufficient fluorinated nanoplatform for enhanced photodynamic eradication of bacterial biofilms

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Abstract
Hypoxia, an important characteristic of bacterial biofilms, can hinder the generation of reactive oxygen species (ROS) in photodynamic therapy (PDT), leading to reduced therapeutic efficacy of PDT. In order to address this issue, fluorinated liposome was fabricated as an oxygen-sufficient nanoplatform for enhanced photodynamic eradication of bacterial biofilms. The liposomes (denoted as Lip-Ce6-PFH@O2) were prepared by co-encapsulation of O2 carrier perfluorohexane (PFH) and photosensitizer chlorin e6 (Ce6). Lip-Ce6-PFH@O2 could achieve efficient biofilm penetration due to the positively charged surface. The hypoxic microenvironment of biofilms would then be relieved, leading to the generation of more ROS under laser irradiation. Therefore, the bactericidal capability of PDT could be significantly improved because of the co-delivered O2 carrier PFH. Lip-Ce6-PFH@O2 exhibited much better antibiofilm ability than that of Lip-Ce6 both in vitro and in vivo. Meanwhile, Lip-Ce6-PFH@O2 also effectively alleviated inflammation symptoms and accelerated wound healing in the mice model. In general, this study provides a new paradigm to enhance the therapeutic efficacy of PDT for efficient biofilm eradication.

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