Poly(l-ornithine)-Grafted Zinc Phthalocyanines as Dual-Functional Antimicrobial Agents with Intrinsic Membrane Damage and Photothermal Ablation Capacity

Abstract

Multifunctional antimicrobial peptides that combine the intrinsic microbicidal property of cationic polypeptide chains and additional antibacterial strategy hold promising applications for the treatment of infections caused by antibiotic-resistant bacteria, especially "superbugs". In the present study, star-shaped copolymers ZnPc-g-PLO with a zinc phthalocyanine (ZnPc) core and four poly(L-ornithine) (PLO) arms were designed, synthesized, and evaluated as dualfunctional antimicrobial agents, that is, intrinsic membrane damage and photothermal ablation capacity. In an aqueous solution, amphiphilic ZnPc-g-PLO molecules self-assemble into nanosized polymeric micelles with an aggregated ZnPc core and star-shaped PLO periphery, where the ZnPc core exhibits appreciable aggregation-induced photothermal conversion efficiency. In the absence of laser irradiation, ZnPc-g-PLO micelles display potent and broad-spectrum antibacterial activities via physical bacterial membrane disruption as a result of the high cationic charge density of the star-shaped PLO. Upon laser irradiation, significant improvement in bactericidal potency was realized due to the efficacious photothermal sterilization from the ZnPc core. Notably, ZnPc-g-PLO micelles did not induce drug-resistance upon subinhibitory passages. In summary, dualfunctional ZnPc-g-PLO copolymers can serve as promising antibacterial agents for the treatment of infectious diseases caused by antibiotic-resistant bacteria.

Phthalocyanine‐Based Photosensitizers for Photodynamic Antibacterial Therapy

“…The high cationic charge density of ZnPc-g-PLO micelles endowed them with potent and broad-spectrum antibacterial activities by physically disrupting bacterial membranes in the absence of laser irradiation, and the aggregation-induced high photothermal conversion efficiency of the ZnPc core resulted in a significant enhancement in bactericidal potency through effective photothermal sterilization. [22] Lee and his colleagues found that boronic acid-functionalized zinc(II) phthalocyanine (PcN4-BA) can serve as a novel PS for aPDT. The aggregation generally results in a substantial reduction in the generation of ROS derived from Pcs, exerting an adverse impact on photodynamic therapy.…”

“…[27] Magadla et al synthesized a range of ZnPcs with varying cation numbers (Figure 3a) and encapsulated them within SiNPs to prevent or reduce ZnPcs' aggregation and The preparation of ZnPc-g-PLO micelles and their mechanism of antibacterial activity. [22] Copyright (2021), with permission from American Chemical Society. (b) The schematic illustration of the nanostructured self-assembly of PcN4-BA.…”

“…synthesized ZnPcs substituted with four poly(L‐ornithine) (PLO) arms and assembled ZnPc‐g‐PLO into nanosized polymeric micelles with an aggregated ZnPc core and star‐shaped PLO periphery (Figure 2a). The high cationic charge density of ZnPc‐g‐PLO micelles endowed them with potent and broad‐spectrum antibacterial activities by physically disrupting bacterial membranes in the absence of laser irradiation, and the aggregation‐induced high photothermal conversion efficiency of the ZnPc core resulted in a significant enhancement in bactericidal potency through effective photothermal sterilization [22] …”

“…Figure 2. (a)The preparation of ZnPc-g-PLO micelles and their mechanism of antibacterial activity [22]. Copyright (2021), with permission from American Chemical Society.…”

Recent Advances in Antimicrobial Nano-Drug Delivery Systems

“…Multifunctional antimicrobial peptides that combine the intrinsic microbicidal property of cationic polypeptide chains and additional antibacterial strategy hold promising applications for the treatment of infections caused by antibiotic-resistant bacteria, especially “superbugs”. Zheng et al [ 83 ] designed and synthesized a star-shaped copolymer ZnPc-g-PLO with a zinc phthalocyanine (ZnPc) core and four poly(l-ornithine) (PLO) arms as a bifunctional antibacterial agent, i.e., intrinsic membrane damage and photothermal ablation capability. In an aqueous solution, amphiphilic ZnPc-g-PLO molecules self-assemble into nanosized polymeric micelles with an aggregated ZnPc core and star-shaped PLO periphery, where the ZnPc core exhibits appreciable aggregation-induced photothermal conversion efficiency.…”