Figure 8. (a) Infrared thermal images of two mice injected with either
the CuCo2S4 NCs (the right one,
indicated region 12) or PBS (the left one, indicated region 11),
respectively, irradiated with an 808 nm laser (0.56 W
cm−2) for 60 s. (b) Histological analysis of carotid
artery stenosis in a mouse model. (c) H&E staining images of the main
visceral organs in the Apo E −/− mice treated with the
CuCo2S4 NCs after MPTT. Reproduced from
Ref. [208] with permission. Copyright 2019 Royal Society of
Chemistry.
4.3. Wound healing
Bacterial infection is one of the main causes of human death.
Microvascular dysfunction caused by hyperglycemia in diabetic patients
leads to slow diabetic wound healing, which significantly increases the
risk of bacterial infection in the process of wound healing. At present,
antibiotics are the most used drugs to deal with bacterial infections in
clinical treatment.[211-213] However, the inappropriate use of
antibiotics leads to the emergence of multi-drug resistant strains such
as methicillin-resistant Staphylococcus aureus
(MRSA), which seriously limits the
therapeutic effect of antibiotics. Therefore, the development of
antibiotic-free antimicrobial agents and strategies is essential for the
management of infected wounds in diabetic patients.[214-216] MPTT
under the stimulation of NIR light can specifically kill pathogenic
bacteria. In addition, MPTT can effectively alleviate the intermolecular
forces or reduce the volume, and local temperature changes can also lead
to structural changes in the hydrogel network, achieving rapid drug
release and reducing the incidence of bacterial infection, thereby
accelerating wound healing. As an important biomaterial, hydrogel has
attracted much attention in the field of biomedicine due to its good
biocompatibility, adjustable degradability, and suitable mechanical
properties. Moreover, hydrogels are porous, highly flexible and can hold
a specific amount of water up to 90%, and these ”soft and wet”
properties provide a living tissue-like environment, thus making them a
suitable biomaterial for healthcare.[217-220] Therefore, many
researchers have proposed this ”two birds with one stone” strategy:
after eliminating diseased cells with PTT, the hydrogel is used for
tissue repair, to exert a synergistic therapeutic effect under laser
irradiation.
In the study by Xu et al., the researchers aimed to develop a
nanocatalytic antibacterial system for promoting wound healing while
addressing bacterial infections. The system utilized a combination of
MPTT and nanocatalysis, with a focus on rapid bactericidal action and
tissue repair. The core of the system consisted of hydroxyapatite (HAp)
nanoparticles incorporated with gold NPs (Au-HAp), further coated with a
layer of PDA to enhance their functionality. The PDA@Au-HAp NPs were
designed to generate hydroxyl radicals (•OH) through catalysis of a
small concentration of H2O2. These •OH
radicals were effective in rendering bacteria more vulnerable to
temperature changes. The antibacterial efficacy of the nanoparticles was
demonstrated against Escherichia coli and Staphylococcus aureus, with
high bacterial reduction rates of 96.8% and 95.2%, respectively.
Importantly, this bactericidal effect occurred at a controlled
photo-induced temperature of 45°C, which was shown to cause no damage to
normal tissues. The combination of catalysis and MPTT provided a
synergistic antibacterial effect that was safe, rapid, and highly
effective compared to •OH or MPTT alone. Furthermore, the PDA@Au-HAp
stimulated the expression of tissue repair-related genes, facilitating
the formation of granulation tissues and collagen synthesis, thereby
accelerating the wound healing process.[221] Overall, this research
presents a promising nanocatalytic antibacterial system that combines
MPTT and nanocatalysis to promote wound healing while effectively
addressing bacterial infections. Yuan et al. developed an all-in-one
phototherapeutic nanoplatform for the elimination of biofilms,
challenging to treat the resistance of antibiotics and other
conventional therapies. Biofilms are communities of bacteria that can
form on various surfaces, including medical implants, and are associated
with chronic infections. The developed nanoplatform, termed AI-MPDA,
consisted of several key components: Mesoporous Polydopamine (MPDA)
served as the core material for the nanoplatform and provided a stable
structure for further modifications. L-Arginine (L-Arg) was performed to
introduce a key therapeutic component to produce NO, a molecule with
antibacterial properties. ICG was adsorbed onto the MPDA surface via π−π
stacking that can generate ROS upon exposure to NIR light. The
nanoplatform generated heat upon NIR irradiation, which contributed to
the MPTT component of the treatment. Importantly, the treatment
temperature was kept relatively low (≤45°C) to minimize damage to
surrounding healthy tissues. The combination of these therapeutic
actions resulted in the effective elimination of biofilms, including the
destruction of bacterial membranes. Importantly, the AI-MPDA
nanoplatform demonstrated good compatibility with human cells. In
addition to its efficacy in biofilm elimination, NIR-irradiated AI-MPDA
were also shown to prevent bacterial colonization and promote rapid
wound healing in infected wounds.[222] Overall, this study presented
an innovative mild phototherapeutic platform, AI-MPDA, as a reliable
tool for combating already-formed biofilms in clinical applications. The
platform’s ability to combine PTT, PDT, and NO release makes it a
promising approach for addressing biofilm-related infections. Qiang et
al. proposed a novel approach for the controlled and gentle killing of
bacteria using MPTT. Unlike
traditional PTT methods that often lead to bacterial cell necrosis, this
approach aimed to induce a mode of bacterial cell death resembling
apoptosis, where the bacterial cell membranes remain intact, but the
bacteria are unable to proliferate. MPTT did not directly destroy the
outer membranes of the bacteria but instead triggered the gradual efflux
of calcium ions (Ca2+) and magnesium ions
(Mg2+) from the bacterial intracellular content. While
the outer membranes remained intact, the treatment caused dynamic
variations in the surface micromorphology of the bacterial membranes.
The study also demonstrated that the viability of E. colibacteria could be dynamically changed through different temperature
ranges. This controlled MPTT strategy was found to be more effective in
promoting the healing of wounds in mice when compared to higher PTT
temperatures (e.g., 58 °C).[223] This innovative approach offers
potential applications in wound disinfection and healing in clinical
settings by utilizing a MPTT strategy that selectively targets and
controls bacterial growth while preserving the integrity of tissues. It
represented a promising direction for the development of more gentle and
effective antibacterial therapies. Duan et al demonstrated a novel
approach for advanced antibacterial therapy and wound disinfection using
a carrier system based on porous silicon (PSi) modified with PDA. This
innovative system, referred to as CuPDA-coated PSi microcarrier
(CuPPSi), was designed to possess both photothermal and therapeutic
capabilities for enhanced antibacterial effects and wound healing. CuPPS
allowed for the incorporation of therapeutic components while
maintaining the PSi’s mesoporous structure. CuPPSi exhibited a
significant photothermal effect when exposed to NIR laser irradiation.
This property was attributed to the presence of PDA on the carrier’s
surface, enabling efficient conversion of NIR light into heat. CuPPSi
demonstrated stimuli-responsive drug release behavior, triggered by
factors such as pH, ROS, and NIR laser irradiation. This feature allowed
for controlled and targeted release of antibacterial agents, including
Cu2+ ions and curcumin (Cur). CuPPSi-Cur platform
exhibited a synergistic antibacterial effect, effectively killing over
98% of both Staphylococcus aureus and Escherichia coli bacteria at a
MPTT temperature of approximately 45 °C.[224] The study highlighted
the potential of the CuPPSi-Cur platform as an intervention for
amplifying wound disinfection in clinical settings. By combining the
photothermal and therapeutic effects, this innovative approach offers a
promising strategy for addressing bacterial infections and promoting
wound healing with improved precision and efficacy. In the study
conducted by Shi et al., the researchers developed a biomimetic
non-antibiotic nanoplatform for the low-temperature photothermal
treatment of urinary tract infections (UTIs) caused byuropathogenic Escherichia coli (UPEC). This innovative
nanoplatform addressed the challenges associated with antibiotic
resistance and the potential tissue damage caused by high local
temperatures in traditional PTT. The nanoplatform consisted of two main
components: a PDA photothermal core and a biphenyl mannoside (Man)
shell. The Man shell was designed with multivalent high-affinity binding
to UPEC, ensuring effective targeting. The PDA-Man nanoplatform was
designed to deliver high photothermal energy selectively to the
bacterial clusters. This allowed for the effective photothermal
bactericidal effect within the bacterial area while maintaining a low
temperature in the surrounding environment. In UTI models, the
fabricated nanoplatform demonstrated excellent photothermal bactericidal
effects, achieving approximately 100% bacterial elimination.[225]
The MPTT nanoplatform provides a promising strategy for the elimination
of bacteria in clinical applications, particularly for the treatment of
UTIs caused by UPEC. By avoiding high local temperatures, this approach
minimizes the risk of tissue damage while effectively targeting and
eliminating bacteria. Overall, this study presented an innovative and
clinically relevant approach to combat UTIs, addressing the growing
concern of antibiotic resistance and improving the precision and
efficacy of bacterial elimination using MPTT. Zhu et al. proposed a
novel antibiofilm strategy called Iron-Actuated Janus Ion Therapy
(IJIT), which aimed to regulate iron metabolism in both bacterial
biofilm and immune cells. This approach involved the use of a biofilm
microenvironment (BME)-responsive photothermal microneedle patch
(FGO@MN) as a key component. These nanomaterials were encapsulated in
methacrylated HA needle tips, which exhibited a photothermal effect. The
combination of FGO@MN-induced thermal sensitization and MPTT led to
increased iron uptake within bacterial biofilms. This intracellular iron
overload subsequently induced a ferroptosis-like form of cell death. The
study also demonstrated that iron-nourished neutrophils in the BME were
rejuvenated, reactivating their suppressed antibiofilm function. The
combined approach of heat stress-triggered iron interference and
iron-nutrient immune reactivation resulted in the elimination of more
than 95% of bacterial biofilm infection.[226] This study presented
a promising antibiofilm strategy that utilizes the unique properties of
nanomaterials, photothermal effects, and iron regulation to combat
bacterial biofilm infections effectively. The IJIT approach offers a
potential solution to the challenge of treating persistent and
antibiotic-resistant biofilm-related infections. Lin et al. introduced a
novel approach to combat bacterial infections and expedite wound
healing. They utilized hollow silver-gold alloy NPs loaded with the
photosensitizer Ce6 (Ag@Au-Ce6 NPs), which were designed to integrate
MPTT and PDT. Ag@Au-Ce6 NPs were effective in killing bacteria,
including both free-floating and surface-colonizing bacteria on wounded
skin. The combined use of MPTT and PDT contributed to efficient
bacterial eradication. Treatment with Ag@Au-Ce6 NPs promoted various
aspects of wound healing, including the migration of epithelial cells
and the formation of new blood vessels.[227] The results of this
study suggest that Ag@Au-Ce6 NPs hold significant promise for biomedical
applications due to their ability to combat bacterial infections and
enhance wound healing. The study underscores the potential of these
nanoparticles for future medical applications.
Mei et al. presented a strategy for eradicating bacterial-associated
infections (BAI) at all stages. They introduced a biofilm
microenvironment (BME)-responsive copper-doped polyoxometalate clusters
(Cu-POM) combined with MPTT and macrophage immune reactivation. The
designed Cu-POM nanoclusters that respond to the specific conditions of
the biofilm microenvironment (BME) can serve a dual function in CDT and
MPTT. The increased flux of Cu-POM into bacterial cells resulted in
intracellular Cu-POM overload. This interferes with bacterial
metabolism, particularly the tricarboxylic acid (TCA) cycle, and leads
to the accumulation of peroxides, ultimately causing a cuproptosis-like
death in bacteria. The study demonstrated that CDT reactivated
macrophages, enhancing their ability to scavenge planktonic bacteria
that may escape from disintegrating biofilms. This is achieved through
increased chemotaxis and phagocytosis.[228] The combination of
Cu-POM-induced bacterial cuproptosis-like death, coupled with the
reactivation of macrophage immune responses, facilitates the clearance
of BAIs at all stages, providing a comprehensive approach to infection
control. Zhao et al. developed a versatile hydrogel dressing
(rGB/QCS/PDA–PAM) with skin adaptiveness for treating infected wounds
effectively and safely. The hydrogel dressing was composed of various
components, including phenylboronic acid-functionalized graphene (rGB),
oxadiazole-decorated quaternary carboxymethyl chitosan (QCS), and a
polydopamine–polyacrylamide (PDA–PAM) network. These components were
integrated through multiple covalent and noncovalent bonds. The hydrogel
exhibited flexible mechanical properties, making it suitable for use on
dynamic wounds. It adhered well to tissue and possesses excellent
self-healing capabilities. The presence of phenylboronic acid on the
surface of rGB allowed the hydrogel to specifically capture bacteria.
This property was particularly useful in targeting and controlling
infections. QCS enhanced bacterial vulnerability to
MPTT. The hydrogel demonstrated
efficient MPTT antibacterial activity. When applied to MRSA-infected
wounds in vivo, the hydrogel dressing accelerates tissue regeneration.
It promoted the growth of an intact epidermis, encouraged collagen
deposition, and facilitated angiogenesis.[229] The hydrogel dressing
is a versatile solution that exhibits inherent antibacterial activity.
Its adaptability to dynamic wounds, specific bacteria capture, and
effective MPTT make it a promising option for treating wounds infected
with drug-resistant bacteria. This research has significant potential
for clinical applications in wound care.