ll

Article
AIEgen-based smart system for fungal-
infected wound monitoring and on-demand
photodynamic therapy
Kun Zhou, Siyuan Wang, Letian
Xu, ..., Guoqing Zhang, Zheng
Zhao, Ben Zhong Tang

zhaozheng@cuhk.edu.cn (Z.Z.)
tangbenz@cuhk.edu.cn (B.Z.T.)

Highlights
Unique AIEgens behave in
sensitive pH response to C.
albicans

The AIEgen-based smart system

monitors fungal infection via a
cellphone

Portable and on-demand PDT is

achieved in an AIEgen-based
smart system

Zhou et al. develop an AIEgen-based smart wound-dressing system for fungal-

infected wound monitoring and on-demand photodynamic therapy. The smart
system generally contains an AIEgen-doped liquid dressing and an image
identification system on a smartphone and demonstrates a unique AIEgen-based
smart film sensor and highly efficient cellphone controllable photodynamic
therapy.

Zhou et al., Matter 6, 1–14

October 4, 2023 ª 2023 Elsevier Inc.
https://doi.org/10.1016/j.matt.2023.06.028
 Please cite this article in press as: Zhou et al., AIEgen-based smart system for fungal-infected wound monitoring and on-demand photodynamic
therapy, Matter (2023), https://doi.org/10.1016/j.matt.2023.06.028

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Article
AIEgen-based smart system
for fungal-infected wound monitoring
and on-demand photodynamic therapy
Kun Zhou,1,2,3 Siyuan Wang,1 Letian Xu,2 Haowen Li,1 Yuheng Wang,6 Zijie Qiu,1 Guoqing Zhang,3
Zheng Zhao,1,4,5,* and Ben Zhong Tang1,2,5,7,*

SUMMARY PROGRESS AND POTENTIAL

Smart portable systems with integrated diagnosis and treatment Fungi have been recognized as a
play an important role in modern life. Real-time evaluation of wound major pathogen associated with
infection and providing on-demand therapies with a smart wound- chronic and ultimately fatal
dressing system is a promising way to treat wound infection infections in critically ill patients.
and alleviate the problem of antibiotic resistance. Herein, a smart Clinical testing requires multiple
portable system that equips fungi-sensitive aggregation-induced steps and is time consuming,
emission luminogens (AIEgens), a mini-double light channel on a which seems more inconvenient
cellphone, and intelligent software is presented to monitor fungal to patients, especially in an
infection within seconds and give 1-min photodynamic therapy via epidemic outbreak. To relieve
low-power white light irradiation (5 mW cm 2) and antifungal activ- medical stress, we developed an
ities over 96%, which realized 1-week wound healing. The smart sys- AIEgen-based smart wound-
tem, integrated with remote communications and image analysis dressing system for fungal-
software, can realize wireless data transmission, infection degree infected wound monitoring and
analysis, and medical advice given by doctors through the internet. on-demand photodynamic
This smart system relieves the emergency of world antibiotic resis- therapy for the first time. The
tance and lays a foundation for developing smart wound dressing smart system generally contains
and potential applications in preclinical research and diagnostics. an AIEgen-doped liquid dressing
and an image identification
INTRODUCTION system on a smartphone. It is a
significant technological advance,
Drug-resistant microbial infection has become a worldwide public health problem.1
as we demonstrate a unique
Compared with gram-negative and gram-positive bacteria, fungi have a rigid cell
AIEgen-based smart film sensor
wall composed of glycoproteins and polysaccharide polymers, which causes a
and highly efficient cellphone
strong barrier to drug penetration.2–4 Therefore, fungal infection is more difficult
controllable photodynamic
to cure and is prone to drug resistance.5,6 Early detection and intervention are
therapy. This discovery lays the
necessary.7 Currently, clinical diagnostic methods in vitro are usually sampled and
foundation for new-generation
cultured, which is cumbersome and time consuming.8,9 Although early warning
home healthcare devices, novel
and diagnosis of fungal infection are critical, only a limited number of patients are
smart therapeutic models, and
willing to carry out the clinical test. In particular, when medical resources are
different microbial-infected
stretched with the outbreak of infectious diseases, the fungal infection test in the
disease treatment.
hospital seems more inconvenient to patients, especially patients with chronic
infection and postoperative trauma treatment.10,11

To relieve medical stress, scientists have developed a series of intelligent wound-

monitoring devices based on electrochemical sensors to help patients monitor
wounds at home.12,13 The physiological data of the wound, such as pH,14,15 temper-
ature,16,17 pressure,18–20 etc., are continuously collected through flexible elec-
trodes.21–24 The data are sent to doctors through wireless transmission technology
who then provide medical guidance remotely.25–27 This invention significantly
reduced both consulting hours and medical costs.28,29 However, electrochemical

Matter 6, 1–14, October 4, 2023 ª 2023 Elsevier Inc. 1

 Please cite this article in press as: Zhou et al., AIEgen-based smart system for fungal-infected wound monitoring and on-demand photodynamic
therapy, Matter (2023), https://doi.org/10.1016/j.matt.2023.06.028

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Article

sensors increase the cost of wound dressing and require the introduction of a detec-
tion electrode to contact the wound, which may cause discomfort in patients and
secondary infection.30,31 Fluorescent film sensors as low-cost and non-contact
sensors are easy to visualize by color based on chemical reaction and image recog-
nition.32,33 Fluorescent film sensors usually equips an image analysis software to
digitalize wound-dressing changes and give a scientific judgment in early infec-
tion.34 Wound dressing integrated with fluorescent film sensors exhibits different
colors or emissions due to the response of sensing molecules within the wound dres-
sing to the infected microenvironments (e.g., pH, temperature, etc.).35,36 The key
components of the visual sensor system were fluorescent molecules loaded on
wound dressing that can sense the microenvironment change. However, the
above-reported wound dressings show a significant bacterial-infected response,
but there is still no suitable wound dressing for fungi-infected monitoring and treat-
ment so far. Thus, developing smart wound dressing for fungi monitoring and treat-
ment based on fluorescent film sensors is more meaningful.

Generally, traditional fluorescent molecules are usually aggregation-induced

quenching (ACQ) molecules, making it difficult to exert an ideal effect in a film
state.37,38 Aggregation-induced emission luminogens (AIEgens) are a kind of lumi-
nescent material that hold the advantages of strong aggregate emission,39–43,44,45
superior photostability,46,47 and aggregation-enhanced reactive oxygen species
(ROS) generation,48,49 which could be applied in fluorescent sensors,50–55 microbial
detection,56–58 photothermal59 and photodynamic therapy.60,61 Besides, scientists
have developed various nanomaterial-loaded wound dressings for antibacterial ther-
apy based on strong ROS generation such as ZnO hybrid Fe2O3 superlattice nano-
films,62 Ti3C2 nanosheets,63 zinc porphyrin-based metal-organic frameworks
(MOFs) and zinc oxide,64 magnetic composites,65,66 Garcinia nanoparticles,67 natural
tea nanodots, etc.68 However, all of them showed great antibacterial activity instead
of antifungal activities. Unlike bacteria, fungi have a rigid cell wall, which causes a
strong barrier to drug penetration and is prone to drug resistance.2–4 Thus, it is a
big challenge to develop a smart system for fungi-infected monitoring and therapy.
In this work, by comprehensive utilization of the merits of AIE materials, we worked
with the AI (artificial intelligence) team to address the current blind spot in the devel-
opment of smart wound dressings (fungal monitoring and treatment) and co-devel-
oped an AIEgen-based smart wound dressing system for fungal-infected wound 1School of Science and Engineering, Shenzhen
monitoring and on-demand photodynamic therapy. In general, the smart system Institute of Aggregate Science and Technology,
The Chinese University of Hong Kong, Shenzhen
contains AIEgen-doped wound dressing and an image identification system equip- (CUHK-Shenzhen), Guangdong 518172, China
ped on a smartphone, which avoids the introduction of detection electrodes and 2Guangdong Provincial Key Laboratory of
power supply systems, greatly reducing the cost of smart dressing. Moreover, com- Luminescence from Molecular Aggregates,
South China University of Technology,
mercial liquid dressing (LD) was employed as a substratum to develop pyridine- Guangzhou 510640, China
substituted benzothiadiazole derivative (TBSMPPy) LD. The fabricated TBSMPPy 3University
of Science and Technology of China,
LD possesses good adhesion, flexibility, and film-forming properties. It acts as a fluo- Hefei, Anhui 230026, China
rescent sensor and photosensitizer to detect the C. albicans (usually infects the skin 4HKUST-Shenzhen Research Institute, South Area
Hi-Tech Park, Nanshan, Shenzhen, Guangdong
and mucous tissue) growth environment (pH around 5.5) and exert photodynamic
Province 518057, China
therapy. UV and white light sources were equipped on the smartphone to work as 5AIEInstitute, Guangzhou Development District,
an excitation source to achieve the detection of fluorescence changes on the wound Huangpu, Guangdong 510530, China
dressing. The mobile phone took photos and uploaded them to Cloud software to 6Faculty of Electrical Engineering and Computer
digitize the infected degree and further feed it back to the mobile phone. The patient Science, Ningbo University, Ningbo 315211,
China
could evaluate the extent of wound infection and switch the white light for photody- 7Lead contact
namic therapy according to the analytical results and the recommendation of the app
*Correspondence:
(Figure 1). This smart system can also allow doctors to monitor the patient’s wound zhaozheng@cuhk.edu.cn (Z.Z.),
and give treatment plans according to software analysis results, significantly tangbenz@cuhk.edu.cn (B.Z.T.)
https://doi.org/10.1016/j.matt.2023.06.028

2 Matter 6, 1–14, October 4, 2023

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Figure 1. Working principle

AIEgen-based smart system for fungal-infected wound monitoring and on-demand photodynamic therapy.

improving medical efficiency and providing scientific technical support for intelligent
home medical care development.

RESULTS AND DISCUSSION

Photophysical properties
The target molecule was synthesized according to the synthetic route illustrated in
Scheme S1 and characterized by 1H, 13C nuclear magnetic resonance (NMR) and
high-resolution mass spectra (Figures S14–S21). The optical properties were inves-
tigated by UV-visible (UV-vis) and photoluminescence (PL) spectra. As shown in Fig-
ure 2A, TBSMPPy presented broad and strong absorption in the visible region, and
the maximum absorption wavelength was 410 nm with a molar absorptivity of 104
M 1cm 1. Figure 2B shows that the emission maximum of TBSMPPy was 678 nm in
DMSO solution, which was favorable to avoid the interference of bioluminescence
from skin, hair, etc.69–71 Figures 2C and S1 indicate that TBSMPPy exhibited typical
AIE features. Fluorescence could hardly be observed when dissolved in a good sol-
vent, DMSO, whereas a strong aggregate emission with 120 times the intensity
enhancement appeared when the fraction of the poor solvent, water, reached
99% (Figure 2C). The emission maximum of TBSMPPy in the aggregate state shifted
to 602 nm, indicating that the molecules within the aggregates became more rigid
due to the restriction of excited-state molecular motion. Besides, with the

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Figure 2. Photophysical properties and responsiveness of TBSMPPy LD

(A) UV-vis spectra of TBSMPPy in DMSO solution.
(B) PL spectra of TBSMPPy in DMSO solution.
(C) PL spectra of TBSMPPy in DMSO/water mixtures with different fraction of water (f W ). Concentration: 1 mM; lex : 480 nm.
(D) Principle of TBSMPPy film for H + response; inserted photos were taken in different pH environments under UV light.
(E) Normalized grayscale value of TBSMPPy film in different pH environments.
(F) PL spectra of TBSMPPy film in different pH environments.
(G) Plots of relative PL intensity of 2’,7’-dichlorodihydrofluorescein (DCFH) for general ROS detection in the presence of TBSMPPy upon exposure to
white light (5 mW cm 2 ) in different pH environments. I0 and I are the PL intensities of the indicator before and after irradiation, respectively. TBSMPPy
stock solution concentration: 1 mM, final work concentration: 10 mM.
(H) Plots of relative PL intensity of DCFH in the presence of TBSMPPy in DMSO/water mixtures with different f W. TBSMPPy stock solution concentration:
1 mM, final work concentration: 10 mM, upon exposure to white light (5 mW cm 2 ).

enhancement of the DMSO fraction, the emission of TBSMPPy decreased, suggest-

ing that the molecule had a strong twisted intramolecular charge transfer (TICT) ef-
fect, which commonly works as a quenching factor for the luminescence in a polar
solution. The lifetime tested in the film was 2.3 ns, and the Commission Internatio-
nale de L’Eclairage (CIE) chromaticity diagram showed that TBSMPPy film emitted
bright orange fluorescence (Figures S2 and S3).

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pH responsiveness of TBSMPPy LD in vitro

Subsequently, a pH-responsive test was conducted to evaluate the sensitivity of
TBSMPPy. The fabricated TBSMPPy LD was exposed to different pH environments,
and the PL change was recorded. As illustrated in Figures 2D–2F, the TBSMPPy LD
exhibited macroscopically fluorescence quenching, and the gray value of the film
presented a downward trend (Figures 2D and 2E). PL intensity also showed similar
results, which decreased obviously after TBSMPPy LD was located in pH 5.5 buffer
solution (Figure 2F). The PL change of the TBSMPPy LD was mainly ascribed to the
protonation of the pyridine of TBSMPPy in a pH 5.5 buffer solution, which enhanced
the electron-withdrawing ability of the pyridine moiety and enhanced the TICT effect
(Figures S4 and S5). To demonstrate that this response was identically applicable to
the C. albicans response, the C. albicans suspension was dropped onto the
TBSMPPy LD, and the emission of the TBSMPPy LD was also quenched after a few
seconds with a little redshift from luminous yellow to dark orange (Figure S6). The
superior pH response characteristic suggested the great potential of TBSMPPy in
fungi detection. ROS generation capability endows the therapeutic function of a
smart AIE system. Therefore, the ROS generation capability of the TBSMPPy LD
was evaluated. As the test environment became acidic, the ROS generation of the
TBSMPPy LD gradually increased and reached a stable level at pH 5.5 (Figure 2G).
Moreover, Figure 2H demonstrates that the aggregation benefited ROS generation.
All the above data indicate that the TBSMPPy LD had good performance in ROS gen-
eration, especially in an acid environment, enabling the application of the TBSMPPy
LD for fungal-infected monitoring and therapy.

In vitro photodynamic antifungal therapy

After verification of the ROS generation of the TBSMPPy LD, the antifungal activity of
TBSMPPy was further evaluated under low-power white light irradiation. As shown in
Figure 3A, TBSMPPy presented excellent activity against C. albicans upon white
light irradiation (the killing ratio is 97%), whereas the unirradiated TBSMPPy group
showed a negligible kill ratio (10.3%). To further ensure the highly effective anti-
fungal activity of TBSMPPy, the commercial antifungal agent Diflucan, as a positive
control group, was employed to compare the antifungal activity. The statistical data
(Figure 3B) showed that the killing ratio of the irradiated TBSMPPy group was equal
to the Diflucan-treated group and even superior to the Diflucan group by nearly 10%
(88% for the Diflucan-treated group). The excellent antifungal behavior of TBSMPPy
encouraged us to apply it for in vivo fungal-infected wound therapy. The optimal
antifungal condition was thus filtrated. In Figures 3C–3E, the bacterial killing rate
is measured at different TBSMPPy concentrations (0.5–6 mM), different irradiation
power densities (3 7 mW cm 2), and different irradiation times (20 80 s). Finally,
the optimal conditions of 2 mM TBSMPPy, 5 mW cm 2, and 1-min irradiation were
chosen for further in vivo exploration.

Subsequently, the prepared TBSMPPy LD was dropped onto the phalangeal joint to
test its adhesion and flexibility. As shown in Figure 3F, the TBSMPPy LD presented
excellent adhesion, and even the finger bound to 90 without resistance. Moreover,
the UV light image indicated that TBSMPPy was successfully loaded into the LD, and
the homogeneous emission indicated the good distribution of TBSMPPy in the LD.
The UV images also suggested that the TBSMPPy LD held excellent adhesion: even
after the tester wore hand cream on their hand (the blue emission came from the
hand cream), the TBSMPPy LD was still perfectly coated on the finger.

Subsequently, the antifungal activity of the TBSMPPy LD was measured via the former
chosen experimental condition. Figure 3G showed that the irradiated TBSMPPy LD

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Figure 3. In vitro photodynamic antifungal therapy

(A) Photographs of Luria Bertani (LB) plate and biocidal activity of C. albicans with different treatment groups.
(B) Antifungal activities of TBSMPPy and Diflucan with different treatments.
(C–E) Fungal inhibition ratio against C. albicans at different concentrations (C), irradiations (D), and irradiated times (E). Data are shown as mean G SD.
N = 3 per group.
(F) TBSMPPy LD adhering to the skin in its original state and bending under white and UV light.
(G) Inhibition zones for different treatment groups.
(H) Live/dead staining images of L929 cells 1, 2, and 3 days after treatment with TBSMPPy LD. The scale bar is 250 mm.

group had the best antifungal activity against C. albicans, and a broad inhibition zone
and low fungal survival were observed. The blank LD group had no significance with
the blank group, which demonstrated that the strong antifungal activity of the
TBSMPPy LD mainly originated from irradiated TBSMPPy. Under irradiation,

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Figure 4. In vivo fungal-infected wound monitoring via smartphone

(A) Operational procedure for AIEgen-based smart system for fungal-infected theragnostic on
fungal-infected mice; a smartphone took the photos.
(B) Schematic illustration of analysis results plotted by smartphone.

protonated TBSMPPy could generate amounts of ROS, which killed C. albicans via
oxidative stress. These results were consistent with the ROS generation test.

Inspired by the outstanding fungi response and elimination activity of the TBSMPPy
LD in vitro, we supposed that the TBSMPPy LD had great potential for in vivo study.
Therefore, the biocompatibility of the TBSMPPy LD was investigated using skin-
related L-929 cells.72 Figures 3H and S7 illustrate that all groups showed a significant
cell proliferation trend with the increase of culture time. The irradiated TBSMPPy LD
group behaved slightly more proliferatively than the control group (312% for the
irradiated TBSMPPy LD group, 297% for the control group). The good biocompati-
bility of TBSMPPy provided a safety platform for in vivo study.

In vivo fungi-infected wound monitoring via smartphone

To further explore the performance of TBSMPPy in vivo, we established a fungal-in-
fected wound model on mice using C. albicans. The detailed animal experiment pro-
cedure is shown in Figure S8. After the model building was finished, the TBSMPPy LD
was dropped onto the wound, forming the dressing film within 2 min. The AIEgen-
based smart system was then employed to monitor infection in situ. The smartphone
was equipped with two-channel lights (UV and white light), and a mobile phone cam-
era was used to capture the image under the UV channel. Besides, we developed im-
age analysis software and placed it on the Cloud to facilitate image analysis through

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mobile phone networking. After the images were uploaded to the Cloud via cell-
phone through the Internet, the software analysis results were immediately fed
back to the cellphone. According to the results and medical advice, the white light
channel would give on-demand photodynamic therapy (Figure S8). The general
diagnosis and therapeutic process is shown in Figure 4A, and Videos S1, S2, S3,
S4, and S5; after coating the wound area with the TBSMPPy LD, wound photos
were taken by a cellphone camera under UV light, and the photos were uploaded
to the Cloud for analysis. A few seconds later, the results were sent back. If infected,
the dressing on the wound emitted a weak orange light, and the cellphone interface
would exhibit a red color. Furthermore, a normalized gray value of the wound area
was presented, and infected warning and irradiation were recommended (Videos S1
and S3). If uninfected, the wound dressing would present a bright emission, and the
cellphone would give a green background and healthy report (Videos S2 and S4).
The performance of the TBSMPPy LD on mice was similar to in vitro monitor results,
which demonstrated that our designed TBSMPPy LD had a sensitive response to C.
albicans infection in vivo. The enlarged image analysis interface is shown in
Figure 4B.

The different emission from TBSMPPy LD was caused by the AIE molecule TBSMPPy.
For uninfected wounds, the pH was near 6, which would not obviously influence the
fluorescent emission of TBSMPPy. However, if the environment pH became acid, the
pyridine moiety on the TBSMPPy would be protonated with a sharp decline in fluo-
rescence, especially at a pH value of 5.5. This pH value was suitable for C. albicans
proliferation and became an essential indicator for detecting fungal infection.73–75
Moreover, to prove the accuracy of the fluorescence image taken by cellphone for
wound infection analysis, we constructed a control experiment using an external
UV lamp and a digital camera to take fluorescence photos of the wound and then
analyzed the images through software to compare the analysis results of the two ex-
periments. In Figure S9, the TBSMPPy LD coated on infected wounds exhibited a
weak emission and infection warning on the software. The TBSMPPy LD emitted
bright orange-yellow fluorescence and an uninfected reminder for the uninfected
model. These results were consistent with the result outputted from the AIEgen-
based smart system, demonstrating that our smart system was reliable and precise
for C. albicans infection diagnosis and monitoring.

In vivo photodynamic therapy via smartphone

Then, the therapeutic model was turned on for photodynamic therapy against fungal
infections to evaluate the therapeutic effects of an AIEgen-based smart system. The
mice were randomly divided into five groups, with different treatments (infection
group: infected wound without treatment; LD group: wound treated by blank LD;
M-LD group: wound treated by TBSMPPy LD without irradiation; M-LD + L group:
wound treated by TBSMPPy LD with irradiation; and Diflucan group: wound treated
with Diflucan). As illustrated in Figure 5A and Video S5, the white light on the device
was turned on and irradiated for 1 min. The light power used was lower than a cell-
phone flashlight, which is harmless to normal tissue. After irradiation, wound photos
were taken by cellphone to compare the therapeutic effects. As shown in Figure 5B,
the white light-treated TBSMPPy group was recovered 7 days posttreatment, while
the wound closure of the Diflucan-treated group was near 50%, and the M-LD group
had a slight 37% wound closure. The histopathological analysis showed different de-
grees of inflammatory infiltration in groups except for the irradiated M-LD group.
Only this group showed skin appendages such as hair follicles, sweat glands, and
a completed skin full-thickness structure (Figure 5D). The quantitative analysis of
inflammatory factors proved that the irradiated TBSMPPy LD was helpful to

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Figure 5. In vivo photodynamic therapy via smartphone

(A) Photograph of photodynamic therapy via smartphone.
(B) Photographs of wound regions with different treatments and time points. Infection group: infected wound without treatment; LD group: wound
treated by blank LD; M-LD group: wound treated by TBSMPPy LD without irradiation; M-LD + L group: wound treated by TBSMPPy LD with irradiation;
and Diflucan group: positive control, wound treated with Diflucan.
(C) Analysis of wound closure.
(D) H&E and Masson staining for different treatments and periods. The scale bar is 100 mm.
(E) Angiogenesis after transplantation (day 5). CD31 (red); DAPI (blue). The scale bar is 100 mm.
(F and G) Blood vessel (F) density and (G) diameter. Data were collected and analyzed by ImageJ software. Data are shown as mean G SD. N = 6 per
group. NS, not significant. **p < 0.01 and ***p < 0.001.

anti-inflammatory cytokine expression, which inhibited the inflammatory diffusion

and promoted skin regeneration (Figure S10).76,77 The immunofluorescence results
showed that the irradiated TBSMPPy LD significantly promoted angiogenesis of the
infected wound (Figure 5E). The statistical results indicated that the TBSMPPy LD
showed a superior healing effect under irradiation: the blood vessel density was

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10 times and the blood vessel diameter was 2 times that of the infected group
(Figures 5F and 5G).

At the end of the treatment, the overall toxicity of TBSMPPy was investigated. H&E
staining of main organs indicated that the TBSMPPy-treated mice had no significant
difference in pathological morphology between the treated and healthy mice
(Figure S11). Their liver and kidney function and blood routine indicators were within
the normal range, which indicated that the TBSMPPy LD would not cause acute liver
and kidney injury (Figure S12). The weight of the mice was also stable in a normal
range during the treatment (Figure S13). All experimental results prove that the AIE-
gen-based smart system has superior diagnosis and treatment effects and is friendly
to organisms, with great potential for medical transformation.

Conclusion
In summary, we developed a novel AIEgen-based smart system for fungal-infected
wound monitoring and photodynamic therapy by integrating AIEgen-based fluores-
cence monitoring, photodynamic inactivation, and machine learning together
toward a specific species of fungi. Benefiting from the unique fluorescence charac-
teristics, sensitive pH response, and ROS generation capability, TBSMPPy was
successfully utilized in fungal infection monitoring and efficient fungal inhibition (in-
hibition ratio is over 96%). The deep machine learning method had also been used to
intelligentize AIEgens and build an AIEgen-based smart system, realizing a fungal
infection diagnosis within seconds and giving photodynamic therapy (PDT) via cell-
phone. This proof-of-concept invention had been demonstrated in a mice model,
and the in vivo study verified the sensitive fungal-infected response within seconds
as well as efficient therapeutic effects (5 mW cm 2 white light, irradiated for 1 min).
The infected tissue recovered within 1 week, better than the commercial antifungal
agent Diflucan. Moreover, this smart system would enhance communication be-
tween patients and doctors through the Internet for real clinical medical scenarios,
significantly improving medical efficiency. Our findings will undoubtedly inspire
follow-up research work (either from us or others) to understand and build on this
discovery, providing new, exciting opportunities for the application AIE materials
in intelligent home healthcare systems.

EXPERIMENTAL PROCEDURES
Resource availability
Lead contact
Further information and requests for resources and reagents should be directed to
and will be

fulfilled by the lead contact Ben Zhong Tang (tangbenz@cuhk.edu.cn).

Materials availability
The materials can be produced following the procedures in the section on the syn-
thesis and characterization in the supplemental information.

Data and code availability

All data associated with this study are present in the paper or the supplemental
information.

General
All reactions were performed using standard Schlenk and glovebox (Vigor) techniques
under argon atmosphere. THF and toluene were distilled from sodium/benzophenone

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prior to use. All chemicals used in the experiments were purchased from Energy Chem-
ical, Sigma, Thermo Fisher Scientific, and Sangon Biotech. All reagents and solvents
were used as commercially available without further purification. Column chromato-
graphic purification of products was accomplished using 200–300 mesh silica gel.
NMR spectra were measured on a Bruker Avance-400 MHz spectrometer in the solvents
indicated; chemical shifts are reported in units (ppm) by assigning TMS resonance in the
1
H spectrum as 0.00 ppm, DMSO-d6 resonance in the 13C spectrum as 39.50 ppm, and
CDCI3 resonance in the 13C spectrum as 77.16 ppm. UV-vis measurements were per-
formed using a DH-2000-BAL Scan spectrophotometer. Fluorescence measurements
were conducted on a FLS980 system (Edinburgh Instruments) and Horiba PL spectrom-
eter (Fluorolog-3). The cyclic voltammetry (CV) in solution was measured using CHI660E
B157216, with a polished gold electrode as the working electrode, a Pt-net as counter
electrode, and an Ag wire as reference electrode, using ferrocene/ferrocenium (Fc/
Fc+) as the internal standard. High-resolution mass spectra (HRMSs) were collected on
a Bruker maxis ultra high resolution (UHR)-TOF mass spectrometer in an electrosprayio-
nization (ESI)-positive mode. MTT was measured using a microplate reader (HM-SY96A)
supplied by Shandong Hengmei Electronic Technology. Fluorescence microscopy was
measured using a Laite LF200. Confocal laser scanning microscope (CLSM) characteriza-
tion was conducted with a confocal laser scanning biological microscope (Leica TCS SP8
STED 3X). Photographs were taken using a Nikon D5100 digital camera.

Infected wound monitoring via smartphone

After the C. albicans-infected wound model was established, TBSMPPy-loaded LD
was dropped onto the wound. Then, the LD formed a film, and we photographed
the wound area under UV light. The pictures could be uploaded to the Cloud
and analyzed the gray by software (developed by us), which was controlled by smart-
phones via wireless controlling software (ToDesk 4.4.7). After calculation, the soft-
ware presented the grayscale of the wound area and defined the infected or unin-
fected area on the smartphone.

Infected wound therapy via smartphone

When the wound monitoring was finished on the smartphone, the software would give
an irradiation suggestion. Based on this situation, we developed mini portable lighting
equipment containing UV and white LED pumps. Remarkably, this mini lighting could
load on the smartphone. Therefore, turning on the white light would start photody-
namic therapy when the software provided the wound infected analysis results.

Statistics analysis
All quantitative data in this paper were represented as mean values G standard de-
viations. GraphPad Prism software was employed to perform the data processing
and statistical analysis. Statistical values of *p < 0.05, **p < 0.01, ***p < 0.001,
and ****p < 0.0001 were regarded as statistically significant.

SUPPLEMENTAL INFORMATION
Supplemental information can be found online at https://doi.org/10.1016/j.matt.
2023.06.028.

ACKNOWLEDGMENTS
We thank the Materials Characterization and Preparation Center, The Chinese Uni-
versity of Hong Kong, Shenzhen, for materials characterization, and we are grateful
to Xuan Li for her help with high-resolution mass measurements. This work was
partially supported by National Natural Science Foundation of China grant

Matter 6, 1–14, October 4, 2023 11

 Please cite this article in press as: Zhou et al., AIEgen-based smart system for fungal-infected wound monitoring and on-demand photodynamic
therapy, Matter (2023), https://doi.org/10.1016/j.matt.2023.06.028

ll
Article

(52003228 and 52273197); the Shenzhen Key Laboratory of Functional Aggregate

Materials (ZDSYS 20211021111400001); the Science, Technology and Innovation
Commission of Shenzhen Municipality (JCYJ 2021324134613038, KQTD
20210811090142053, JSGG 20220606141800001, GJHZ 20210705141810031,
and JCYJ20200109110608167); the Innovation and Technology Commission (ITC-
CNERC14SC01); the China Postdoctoral Science Foundation (2022M713022); the
Open Fund of Guangdong Provincial Key Laboratory of Luminescence from Molec-
ular Aggregates (2021-kllma-08); and Guangzhou 510640, China (South China Uni-
versity of Technology).

AUTHOR CONTRIBUTIONS
K.Z., Z.Z., and B.Z.T. conceived the idea for the study. K.Z. prepared the samples and
animal experiments. K.Z. and S.W. analyzed experiment data. L.X. conducted and
analyzed the optical spectra. H.L. clipped videos. Y.W. developed photo analysis
software. K.Z., Z.Z., and B.Z.T. wrote the manuscript. K.Z., L.X., S.W., H.L., Y.W.,
Z.Q., G.Z., Z.Z., and B.Z.T. revised and polished the manuscript. All authors dis-
cussed, commented on, and agreed on the manuscript.

DECLARATION OF INTERESTS
B.Z.T., Z.Z., and K.Z. have submitted a China patent application (no.
202310610042.6), which contains the fabrication of the technique utilized in this
paper.

Received: May 5, 2023

Revised: June 12, 2023
Accepted: June 19, 2023
Published: July 19, 2023

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