Photoenhanced Dual-Functional Nanomedicine for Promoting Wound Healing: Shifting Focus from Bacteria Eradication to Host Microenvironment Modulation

Abstract

Pathogenic bacterial infection has become a serious medical threat to global public health. Once the skin has serious defects, bacterial invasion and the following chain reactions will be a thorny clinical conundrum, which takes a long time to heal. Although various strategies have been used to eradicate bacteria, the treatment which can simultaneously disinfect and regulate the infection-related host responses is rarely reported. Herein, inspired by the host microenvironment, a photoenhanced dual-functional nanomedicine is constructed (Hemin@Phmg-TA-MSN) for localized bacterial ablation and host microenvironment modulation. The “NIR-triggered local microthermal therapy” and positively charged surface endow the nanomedicine with excellent bacterial capture and killing activities. Meanwhile, the nanomedicine exhibits broad-spectrum reactive oxygen species (ROS) scavenging activity via the synergistic effect of hemin and tannic acid with photoenhanced electron and hydrogen transfers. Furthermore, the in vivo experiments demonstrate that the dual-functional nanomedicine not only presents robust bacterial eradication capability, but also triggers the oxidative stress and inflammatory microenvironment regulation. The work not only shows a facile and effective way for infected wound management but also provides a new horizon for designing novel and efficient anti-infection therapy shifting focus from bacteria treatment to host microenvironment modulation.

A Nanohook‐Equipped Bionanocatalyst for Localized Near‐Infrared‐Enhanced Catalytic Bacterial Disinfection

“…[ 3 , 4 , 5 , 6 , 7 , 8 , 9 ] In particular, nanomaterials that can mimic oxidoreductases like peroxidase (POD), oxidase (OXD), and catalase (CAT) have sparked increasing interest because they can be used to fine‐tune local ROS levels for satisfactory bactericidal outcomes. [ 10 , 11 , 12 , 13 , 14 , 15 ] But these oxidoreductase‐mimicking nanomaterials, also known as bionanocatalysts, can show undesirable off‐target activity during in vivo biofilm treatment, leading to unpredictable toxicity. [ 16 , 17 ] Therefore, the ideal bionanocatalyst will not only deliver strong catalytic‐reaction‐based therapeutic effects to biofilm‐infected sites, but will limit its action to these sites while leaving healthy tissues unaffected.…”

Bioinspired Multifunctional Cellulose Nanofibril-Based In Situ Liquid Wound Dressing for Multiple Synergistic Therapy of the Postoperative Infected Wound

“…The temperature of CNF-ILWD@ICG&DOX increased from 41.5 to 48.7 °C and then to 58.6 °C when the power density increased from 0.2 to 0.35 W cm –2 and then to 0.50 W cm –2 in 300 s. In addition, the temperature of CNF-ILWD@ICG&DOX increased rapidly from 30.0 to 45.3 °C (1 mg g –1 ), 48.9 °C (2 mg g –1 ), and 50.2 °C (3 mg g –1 ) with the increase in ICG loading capacity. The heat-responsive tumor cells and bacterial biofilms can be destroyed by thermal ablation at 42–50 °C, while normal tissue cells are unaffected. ,, Therefore, the NIR irradiation-controlled treatment with spatiotemporal selectivity can be achieved by controlling the irradiation time and treatment area of the wound. Interestingly, ICG also produces ROS under NIR laser irradiation; ROS disrupt bacterial cells, increasing the rate of bacterial death; thus, ICG enhances the photothermal effect. , More importantly, the CNF-ILWD@ICG&DOX showed excellent controllable temperature at 42.0 to 50.0 °C, thus enabling a wound treatment strategy that combines PTT and PDT.…”

“…The heatresponsive tumor cells and bacterial biofilms can be destroyed by thermal ablation at 42−50 °C, while normal tissue cells are unaffected. 10,41,42 Therefore, the NIR irradiation-controlled treatment with spatiotemporal selectivity can be achieved by controlling the irradiation time and treatment area of the wound. Interestingly, ICG also produces ROS under NIR laser irradiation; ROS disrupt bacterial cells, increasing the rate of bacterial death; thus, ICG enhances the photothermal effect.…”

Recent Trends in Composite Nanozymes and Their Pro-Oxidative Role in Therapeutics

“…For efficient wound healing, it is important to regulate infection-related host responses besides eradicating bacteria from the wound site. Hemin@Phmg-TA-MSN was demonstrated as a dual-functional nanomedicine ( Wei Z. et al, 2021 ). Graphdiyne-hemin (GDY-hemin) composite was synthesized as a stable nanozyme displaying bacterial cell killing at the wound site and accelerated wound healing mediated by ROS produced by its POD activity ( Ali et al, 2021 ).…”