Porphyrin MOF Dots–Based, Function‐Adaptive Nanoplatform for Enhanced Penetration and Photodynamic Eradication of Bacterial Biofilms

Abstract

Recently, antimicrobial photodynamic therapy (aPDT) has been considered as an attractive treatment option for biofilms ablation. However, even very efficient photosensitizers (PSs) still need high light doses and PS concentrations to eliminate biofilms due to the limited penetration and diffusion of PSs in biofilms. Moreover, the hypoxic microenvironment and rapid depletion of oxygen during PDT severely limit their therapeutic effects. Herein, for the first time, a porphyrin-based metal organic framework (pMOF) dots-based nanoplatform with effective biofilm penetration, self-oxygen generation, and enhanced photodynamic efficiency is synthesized for bacterial biofilms eradication. The function-adaptive nanoplatform is composed of pMOF dots encapsulated by human serum albumin-coated manganese dioxide (MnO 2 ). The pH/H 2 O 2responsive decomposition of MnO 2 in biofilms triggers the release of ultrasmall and positively charged pMOF dots and simultaneously generates O 2 insitu to alleviate hypoxia for biofilms. The released pMOF dots with high reactive oxygen species yield can effectively penetrate into biofilms, strongly bind with bacterial cell surface, and ablate bacterial biofilms. Importantly, such a nanoplatform can realize great therapeutic outcomes for treatment of Staphylococcus aureus-infected subcutaneous abscesses in vivo without damage to healthy tissues, which offers a promising strategy for efficient biofilms eradication.

Biofilm Microenvironment-Responsive Nanotheranostics for Dual-Mode Imaging and Hypoxia-Relief-Enhanced Photodynamic Therapy of Bacterial Infections

“…Hence, the hypoxia microenvironment in biofilms is an intrinsic barrier for aPDT treatment. As reported, excess H 2 O 2 usually exists in biofilm-infected tissues [4,28], in principle, which could be converted to O 2 with the catalysis of MnO 2 . Herein, the potential of MBP-Ce6 NSs to generate O 2 and relieve the hypoxia of biofilm was investigated in a mice model.…”

“…Bacterial infection is a prominent threat for human health. Numerous bacterial infections, including dental caries, cystic fibrosis, pneumonia, otitis media, and especially chronic wounds, usually relate with the formation of bacterial biofilms [1][2][3][4][5]. Biofilm is the aggregated bacterial populations which are usually encapsulated in the extracellular polymeric substances (EPS) and attach to the living or inert surfaces [6,7].…”

“…Since it is difficult for bacteria to develop resistance to 1 O 2 , aPDT is regarded as an effective approach for the drug-resistant bacterial infection [32,36]. However, the therapeutic efficacy of aPDT would be restricted by hypoxia condition in biofilm-infected tissues [4,26] Figure S1, Supporting Information). MnO 2 NSs were prepared by ultrasonication-assisted exfoliation of the as-prepared MnO 2 NSs and followed by gradient centrifugation.…”

“…For pH-responsive Ce6 release study, MRSA biofilms were cultured in a confocal petri dish. The MBP NSs (MnO 2 : 100 μg/mL; Ce6: 80 μg/mL) were cultured with MRSA biofilms at 37°C at different times(1,4,8, and 12 h). After being washed with saline for three times, MRSA biofilms were stained with Calcein-AM (KeyGen BioTech) for 30 min and then imaged by an Olympus IX81 confocal laser scanning microscope.…”

A smart hydrogel for on-demand delivery of antibiotics and efficient eradication of biofilms

“…These compounds or materials could sensitize biofilm infections to conventional antibiotics [6,37]. In addition, photosensitizers and plasmonic nanoparticles were used in combination with lasers to eradicate the biofilm via photodynamic and photothermal therapy [38][39][40][41][42][43]. Extracellular polysaccharides are the major component of biofilm matrix [44].…”