Journal
SCIENCE CHINA-CHEMISTRY
Volume 64, Issue 3, Pages 459-466Publisher
SCIENCE PRESS
DOI: 10.1007/s11426-020-9904-7
Keywords
photodynamic therapy; antibacterial; porphyrin; aggregation caused quenching (ACQ)
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Funding
- National Natural Science Foundation of China [21875063]
- Science and Technology Commission of Shanghai Municipality for the Shanghai International Cooperation Program [19440710600]
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Researchers developed an acid-triggered nanoplatform to enhance photodynamic antibacterial activity by reducing the aggregation of photosensitizers in bacterial acidic microenvironment. The nanoparticles, formed by self-assembly, could rapidly acquire positive charge in acidic bacterial media, effectively adhering to negatively charged bacterial cell membranes.
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 (O-1(2)) 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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