​Hollow silver–gold alloy nanoparticles for enhanced photothermal/photodynamic synergetic therapy against bacterial infection and acceleration of wound healing†

Shanshan Lin,【林珊珊】ab   Hui Chen【陈慧】,ab   Rui Wang【王蕊】,ab   Tongmeng Jiang【蒋童蒙】,ab   Rui Wang【王锐】*ab  and  Fabiao Yu【于法标】  *ab  

 Author affiliations

*Corresponding authors

aKey Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China
E-mail: wangrui@hainmc.edu.cn, yufabiao@hainmc.edu.cn

bEngineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Hainan Functional Materials and Molecular Imaging, College of Pharmacy, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China

Biomater. Sci., 2023,11, 4874-4889
https://doi.org/10.1039/D3BM00567D

Abstract

Bacterial infection seriously restricts the wound healing process due to severe inflammation and delayed wound healing. Unfortunately, the overuse or improper use of antibiotics leads to the advent of multidrug-resistant strains and intractable biofilms, severely affecting the therapeutic effect. Therefore, there is an urgent need to develop antibiotic-free strategies to accelerate the healing process of wounds with bacterial infection. Considering that single photothermal therapy (PTT) or photodynamic therapy (PDT) cannot fully meet the requirements of clinical sterilization and accelerating wound healing, herein, hollow silver–gold alloy nanoparticles immobilized with the photosensitizer molecule Ce6 (Ag@Au-Ce6 NPs) integrated with PTT and PDT are proposed for killing bacteria and accelerating wound healing. The photothermal conversion properties of Ag@Au-Ce6 NPs are obtained using an infrared thermal imager, and the generation of singlet oxygen (1O2) is verified with an 1O2 fluorescent probe DCFH-DA. Manipulated by near-infrared laser triggered mild hyperthermia and limited ROS amount, Ag@Au-Ce6 NPs could effectively kill bacteria that are free and colonized on the surface of wounded skin, promoting epithelium migration and vascularization, further accelerating wound healing, which showed great promise for biomedical application.

Introduction

Bacterial infection exhibits an increasing threat to human health, especially chronic infected wounds that seriously influence people's lives.1,2 Although most skin wounds could be healed within one or two weeks, bacteria infected skin injuries, especially full-thickness wounds, can cause severe pain, sepsis, or even death.3 Bacterial infection seriously restricts the wound healing process due to severe inflammation and delayed wound healing.4 To deal with the bacterial infection of skin wounds, various antibiotics such as penicillin, cephalothin and vancomycin have been widely applied in the clinic. Unfortunately, the overuse or improper use of antibiotics leads to the advent of multidrug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and intractable biofilms, which severely affects the therapeutic effect.5,6 Therefore, there is an urgent need to develop antibiotic-free strategies to accelerate the healing process of wounds with bacterial infection.

Compared to the present method, nanomaterials based on gold and silver exhibit tremendous advantages in preventing wound infections and accelerating wound healing, which is mainly attributed to the tunable physicochemical properties.7 The high surface–volume ratio of nanomaterials can enhance the contact and interaction with bacteria, triggering extensive antibacterial mechanisms and providing better therapeutic efficiency.8 In addition, other factors such as size, shape and surface modification also influence the antibacterial activity of nanomaterials.9 Among the nanomaterials-based therapeutic strategies, photothermal therapy (PTT) and photodynamic therapy (PDT) have aroused increasing attention due to their non-invasiveness, low toxicity and high controllability.10–12

Generally, a photothermal conversion agent can transform light energy into heat energy under near-infrared laser illumination in the PTT process, thus generating local hyperthermia, which can accelerate blood circulation in the wound and further stimulate the proliferation of fibroblasts and reduce inflammation, thus shortening the wound healing process.13 However, a strong laser can cause the local temperature to become too high, which will burn normal tissues during treatment.14 PDT relies on photosensitizers for realizing the conversion from oxygen to reactive oxygen species (ROS) via energy transfer, which can destroy surrounding biomolecules through the oxidation process and kill bacteria.15 However, a large amount of ROS is required to damage most bacteria through PDT alone, while excessive ROS often cause inflammation, fibrosis and even necrosis of normal tissues.16 The single therapy cannot fully meet the requirements of clinical sterilization and wound healing (Scheme 1).

Scheme 1 Schematic illustration of Ag@Au-Ce6 NPs for bacterial eradication and wound healing acceleration. The constructed Ag@Au-Ce6 NPs eliminate planktonic and biofilm bacteria through synergistic photothermal and photodynamic effects, and induce the up-regulation of VEGF and CD31 to promote better wound healing. The illustration was created with the help of BioRender.com.