Centre for Pharmaceutical Innovation, University of South Australia, Clinical and Health Sciences, Adelaide 5000, Australia; Basil Hetzel Institute for Translational Health Research, Woodville 5011, Australia.
Centre for Pharmaceutical Innovation, University of South Australia, Clinical and Health Sciences, Adelaide 5000, Australia.
J Photochem Photobiol B. 2022 Jul;232:112474. doi: 10.1016/j.jphotobiol.2022.112474. Epub 2022 May 18.
Antimicrobial photodynamic therapy (aPDT) has emerged as an innovative strategy to combat antibiotic resistant microbes; yet aPDT efficacies against biofilms are sub-optimal due to inability of photosenstizers to reach microbes embedded in biofilm matrix. To overcome this challenge, liquid crystal lipid nanoparticles (LCNP) were employed in this study as a smart, biocompatible and triggerable delivery system for the new photosensitizer gallium protoporphyrin (GaPP), due to their capabilities in promoting efficient antimicrobial delivery to biofilms. The relationship between GaPP loading of LCNP, reactive oxygen species (ROS) production and the in vitro antibacterial activity against two antibiotic resistant Staphylococcus aureus strains was established. LCNP substantially improved the antibacterial activity of GaPP, completely eradicating S. aureus and MRSA planktonic cultures, using a GaPP concentration of 0.8 μM and light dose 1.9 J/cm. At the same concentration and light dose, unformulated GaPP triggered only a 4 log and 2 log reduction in respective planktonic cultures. Most importantly, the activity of GaPP against biofilms was enhanced by 2-fold compared to unformulated GaPP, reducing the viability of S. aureus and MRSA biofilms by 8 log and 5 log, respectively. The biosafety of photoactivated GaPP-LCNP was evaluated against human fibroblasts, which indicated a high safety profile of the treatment. Therefore, these findings encourage further investigations of GaPP-LCNP as a potential treatment for localized chronic infections.
抗菌光动力疗法 (aPDT) 作为一种对抗抗生素耐药微生物的创新策略而出现；然而，由于光敏剂无法到达嵌入生物膜基质中的微生物，aPDT 对抗生物膜的效果并不理想。为了克服这一挑战，本研究采用液晶脂质纳米粒 (LCNP) 作为一种智能、生物相容和可触发的新型光敏剂镓原卟啉 (GaPP) 传递系统，因为它们具有促进生物膜中有效抗菌药物传递的能力。建立了 LCNP 对 GaPP 的载药量、活性氧 (ROS) 产生与体外抗两种耐抗生素金黄色葡萄球菌 (S. aureus) 菌株的抗菌活性之间的关系。LCNP 大大提高了 GaPP 的抗菌活性，使用 GaPP 浓度为 0.8 μM 和光剂量 1.9 J/cm 时，完全消除了 S. aureus 和 MRSA 浮游培养物。在相同的浓度和光剂量下，未形成配方的 GaPP 仅对浮游培养物分别触发 4 对数和 2 对数的减少。最重要的是，与未形成配方的 GaPP 相比，GaPP 对生物膜的活性提高了 2 倍，分别使 S. aureus 和 MRSA 生物膜的存活率降低了 8 对数和 5 对数。用 GaPP-LCNP 光激活对人成纤维细胞进行生物安全性评估，表明该治疗具有很高的安全性。因此，这些发现鼓励进一步研究 GaPP-LCNP 作为局部慢性感染的潜在治疗方法。
