An acid-triggered porphyrin-based block copolymer for enhanced photodynamic antibacterial efficacy

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Bacterial infection,especially multidrug-resistant (MDR) bacterial infection has threatened public health drastically.Here,we fabricate an “acid-triggered” nanoplatform for enhanced photodynamic antibacterial activity by reducing the aggregation of photosensitizers (PSs) in bacterial acidic microenvironment.Specifically,a functional amphiphilic block copolymer was first synthesized by using a pH-sensitive monomer,2-(diisopropylamino) ethyl methacrylate (DPA) and porphyrin-based methacrylate (TPPC6MA) with poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) as the macromolecular chain transfer agent,and POEGMA-b-[PDPA-co-PTPPC6MA]block copolymer was further self-assembled into spherical nanoparticles (PDPA-TPP).PDPA-TPP nanoparticles possess an effective electrostatic adherence to negatively charged bacterial cell membrane,since they could rapidly achieve positive charge in acidic bacterial media.Meanwhile,the acid-triggered dissociation of PDPA-TPP nanoparticles could reduce the aggregation caused quenching (ACQ) of the photosensitizers,leading to around 5 folds increase of the singlet oxygen (1O2) quantum yield.In vitro results demonstrated that the “acid-triggered” PDPA-TPP nanoparticles could kill most of MDR S.aureus (Gram-positive) and MDR E.coli (Gram-negative) by enhanced photodynamic therapy,and they could resist wound infection and accelerate wound healing effectively in vivo.Furthermore,PDPA-TPP nanoparticles could well disperse the biofilm and almost kill all the biofilm-containing bacteria.Thus,by making use of the bacterial acidic microenvironment,this “acid-triggered” nanoplatform in situ will open a new path to solve the aggregation of photosensitizers for combating broad-spectrum drug-resistant bacterial infection.
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