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

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.