Tea polyphenol-derived nanomedicine for targeted photothermal thrombolysis and inflammation suppression.

Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine's potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.

Polydopamine based photothermal/photodynamic synchronous coating modified intraocular lens for efficient and safer posterior capsule opacification prevention.

Posterior capsule opacification (PCO), as one of the most common late complications after intraocular lens (IOL) implantation in cataract surgery, seriously affects patients' postoperative vision and surgical satisfaction, and can only be treated by laser incision of the posterior capsule. Although drug eluting coating modification have been proved to inhibit PCO effectively, the complicated coating methods and the potential toxicity of the antiproliferative drugs hinders its actual application. In this study, an indocyanine green (ICG) loaded polydopamine (PDA) coating modified IOL (IP-IOL) was designed to prevented PCO. In vitro and in vivo studies have shown that IP-IOL can effectively eliminate lens epithelial cells and significantly reduce the degree of PCO. At the same time, it still has good imaging quality and optical properties. Furthermore, both the near-infrared irradiation and ICG loaded PDA coating modified IOLs have proved to possess high biological safety to eyes. Thus, with easy preparation and safer near-infrared irradiated photothermal/photodynamic synchronous properties, such ICG loaded PDA coating provides an effective yet easier and safer PCO prevention after IOL implantation.

Platelet membrane-coated bio-nanoparticles of indocyanine green/elamipretide for NIR diagnosis and antioxidant therapy in acute kidney injury.

Acute kidney injury (AKI) is a prevalent condition in critically ill patients that is often associated with significant morbidity and mortality. As the lack of effective early diagnosis methods often delays AKI treatment, there is currently no definitive clinical intervention available. In this study, we aimed to address these challenges by developing a nano-system called Platelet membranes-ICG-SS31-PLGA (PISP), which was designed to selectively target to the kidney site, taking advantage of the natural tendency of platelets to accumulate at sites of vascular injury. This approach allowed for the accumulation of PISP within the kidney as the disease progresses. By incorporating ICG, the in vivo distribution of PISP can be observed for NIR diagnosis of AKI. This non-invasive imaging technique holds great promise for early detection and monitoring of AKI. Furthermore, Elamipretide (SS31) acts as a mitochondria-targeted antioxidant that protects against mitochondrial damage and reduces oxidative stress, inflammation, and apoptosis. The combination of diagnostic and therapeutic capabilities within a single nano-system makes the PISP approach a valuable tool for addressing AKI. This intervention helps to prevent the deterioration of AKI and promotes the recovery. STATEMENT OF SIGNIFICANCE.

Indocyanine green based photodynamic therapy for keloids: Fundamental investigation and clinical improvement.

BACKGROUND: Keloid, a prevalent pathological skin lesion, presents significant challenges in terms of treatment efficacy. Photodynamic therapy (PDT), an increasingly popular adjuvant treatment, has shown significant potential in the management of various disorders, including cancer. However, the therapeutic potential of indocyanine green-mediated photodynamic therapy (ICG-PDT) for keloids has not yet been demonstrated. METHODS: In this study, we divided the experimental groups into control group, Photothermal Therapy group, Photodynamic Therapy group, and Combined Therapy group. The in vitro investigation aimed to optimize the clinical application of PDT for keloid treatment by elucidating its underlying mechanism. Subsequently, on this basis, we endeavored to manage a clinical case of keloid by employing surgical intervention in conjunction with modified ICG-PDT. RESULTS: Our investigation revealed an unexpected outcome that ICG-PDT maximally inhibited the cellular activity and migration of keloid fibroblasts only when photodynamic mechanism took effect. Additionally, the induction of autophagy and apoptosis, as well as the inhibition of collagen synthesis, were particularly evident in this experimental group. Furthermore, the above therapeutic effect could be achieved at remarkably low drug concentrations. Building upon the aforementioned experimental findings, we successfully optimized the treatment modality for the latest case and obtained a more favorable treatment outcome. CONCLUSIONS: This study investigated the mechanism of ICG-PDT treatment and optimized the in vivo treatment regimen, demonstrating the significant therapeutic potential of ICG-PDT treatment in clinical keloid treatment.

Perfusion Analysis Using High-Definition Indocyanine Green Angiography in Burn Comb Model.

Indocyanine green angiography (ICGA) has been widely employed for quantitative evaluation of the rat comb burn model, but the imaging equipment, imaging protocol, and fluorescence data interpretation of ICGA remain unsatisfactory. This study aims to provide better solutions for the application of ICGA in perfusion analysis. The rat comb burn model was established under a series of different comb contact durations, including 10, 20, 25, 30, 35, and 40 s. Indocyanine green angiography was used to analyze wound perfusion. In total, 16 rats were divided into ibuprofen and control groups for the burn model, and their perfusion was compared. A total of 16 identical models were divided into standard- and high-dose indocyanine green (ICG) groups, and ICGA was conducted to investigate the dynamic change in wound fluorescence. Escharectomy was performed under real-time fluorescence mapping and navigation. The results showed that a comb contact duration of 30 s was optimum for the burn model. Indocyanine green angiography could accurately evaluate the histologically determined depth of thermal injury and wound perfusion in the rat comb model. Digital subtraction of residual fluorescence was necessary for multiple comparisons of perfusion. Dynamic changes in fluorescence and necrotic tissues were observed more clearly by high-dose (0.5 mg/kg) ICG in angiography. In conclusion, perfusion analysis by ICGA can be used to assess the histologically determined depth of thermal injury and the impact of a specific treatment on wound perfusion. Indocyanine green angiography can help to identify necrotic tissue. The above findings and related imaging protocols lay the foundation for future research.

Microfluidics-Prepared Ultra-small Biomimetic Nanovesicles for Brain Tumor Targeting.

Blood-brain-barrier (BBB) serves as a fatal guard of the central nervous system as well as a formidable obstacle for the treatment of brain diseases such as brain tumors. Cell membrane-derived nanomedicines are promising drug carriers to achieve BBB-penetrating and brain lesion targeting. However, the challenge of precise size control of such nanomedicines has severely limited their therapeutic effect and clinical application in brain diseases. To address this problem, this work develops a microfluidic mixing platform that enables the fabrication of cell membrane-derived nanovesicles with precise controllability and tunability in particle size and component. Sub-100 nm macrophage plasma membrane-derived vesicles as small as 51 nm (nanoscale macrophage vesicles, NMVs), with a narrow size distribution (polydispersity index, PDI: 0.27) and a high drug loading rate (up to 89% for indocyanine green-loaded NMVs, NMVs@ICG (ICG is indocyanine green)), are achieved through a one-step process. Compared to beyond-100 nm macrophage cell membrane vesicles (general macrophage vesicles, GMVs) prepared via the traditional methods, the new NMVs exhibits rapid (within 1 h post-injection) and enhanced orthotopic glioma targeting (up to 78% enhancement), with no extra surface modification. This work demonstrates the great potential of such real-nanoscale cell membrane-derived nanomedicines in targeted brain tumor theranostics.

Hydrogel design to overcome thermal resistance and ROS detoxification in photothermal and photodynamic therapy of cancer.

Responsive heat resistance (by heat shock protein upregulation) and spontaneous reactive oxygen species (ROS) detoxification have been regarded as the major obstacles for photothermal/photodynamic therapy of cancer. To overcome the thermal resistance and improve ROS susceptibility in breast cancer therapy, Au ion-crosslinked hydrogels including indocyanine green (ICG) and polyphenol are devised. Au ion has been introduced for gel crosslinking (by catechol-Au3+ coordination), cellular glutathione depletion, and O2 production from cellular H2O2. ICG can generate singlet oxygen from O2 (for photodynamic therapy) and induce hyperthermia (for photothermal therapy) under the near-infrared laser exposure. (-)-Epigallocatechin gallate downregulates heat shock protein to overcome heat resistance during hyperthermia and exerts multiple anticancer functions in spite of its ironical antioxidant features. Those molecules are concinnously engaged in the hydrogel structure to offer fast gel transformation, syringe injection, self-restoration, and rheological tuning for augmented photo/chemotherapy of cancer. Intratumoral injection of multifunctional hydrogel efficiently suppressed the growth of primary breast cancer and completely eliminated the residual tumor mass. Proposed hydrogel system can be applied to tumor size reduction prior to surgery of breast cancer and the complete remission after its surgery.

ανß3 integrin-targeted ICG-derived probes for imaging-guided surgery and photothermal therapy of oral cancer.

Indocyanine green (ICG), as the only Federal Drug Administration (FDA) approved fluorescence imaging agent, has been widely applied in clinics for near-infrared (NIR) fluorescence imaging-guided surgery and photothermal therapy of cancers. However, its lack of target specificity and poor photo and photothermal stabilities seriously restrict its wide application in clinical practice. Herein, we developed ICG-derived NIR fluorescent probes consisting of a cypate fluorophore and one or two cyclic-(arginine-glycine-aspartic acid) (cRGD) peptides that can specifically target αvß3 integrin for accurate diagnosis and therapy of oral tumors. Probe Cy-2RGD has been demonstrated to possess bright NIR emission, great tumor targeting capability and a photothermal effect. Moreover, it could be successfully used for effective imaging-guided surgical resection as well as photothermal therapy of oral tumors. This work could provide a valuable tool for sensitive detection and accurate treatment of malignant tumors.

Evaluating the clinical efficacy and limitations of indocyanine green fluorescence-guided surgery in childhood hepatoblastoma: A retrospective study.

BACKGROUND: Indocyanine green (ICG) fluorescence guided surgery has been used to treat childhood hepatoblastoma (HB), but the advantages and disadvantages of this technique have not been fully discussed. The purpose of this study is to summarize the experience and to explore the clinical value of this technique for children with HB. METHODS: 45 children with HB who underwent ICG fluorescence guided surgery (n = 22) and general surgery (n = 23) in our center from January 2020 to December 2022 were enrolled retrospectively. RESULTS: All the liver tumors in the ICG group showed hyperfluorescence, including total and partial fluorescent types. With the help of ICG navigation, minimally invasive surgery was performed in 3 cases. 18.2 % of cases with tumors could not be accurately identified under white light, but could be identified by fluorescence imaging. The fluorescent cutting lines of 59.1 % of cases were consistent with the safe cutting lines. In 36.4 % of cases, the fluorescence boundary was not clear because of tumor necrosis. In 36.4 % of cases, the fluorescence could not be detected on the inner edge of the tumors because of the depth. A total of 29 ICG (+) suspicious lesions were found during the operations, of which 5 were true positive lesions. CONCLUSION: ICG fluorescence guided surgery is safe and feasible in children with HB. This technique is helpful for locating tumors, determining margin and finding small lesions with negative imaging, especially in minimally invasive surgery. However, preoperative chemotherapy, tumor necrosis, tumor depth, and ICG administration impact the effect of fluorescence imaging.

Mn2+ /Ir3+ -Doped and CaCO3 -Covered Prussian Blue Nanoparticles with Indocyanine Green Encapsulation for Tumor Microenvironment Modulation and Image-Guided Synergistic Cancer Therapy.

The development of smart theranostic nanoplatforms has gained great interest in effective cancer treatment against the complex tumor microenvironment (TME), including weak acidity, hypoxia, and glutathione (GSH) overexpression. Herein, a TME-responsive nanoplatform named PMICApt /ICG, based on PB:Mn&Ir@CaCO3 Aptamer /ICG, is designed for the competent synergistic photothermal therapy and photodynamic therapy (PDT) under the guidance of photothermal and magnetic resonance imaging. The nanoplatform's aptamer modification targeting the transferrin receptor and the epithelial cell adhesion molecule on breast cancer cells, and the acid degradable CaCO3 shell allow for effective tumor accumulation and TME-responsive payload release in situ. The nanoplatform also exhibits excellent PDT properties due to its ability to generate O2 and consume antioxidant GSH in tumors. Additionally, the synergistic therapy is achieved by a single wavelength of near-infrared laser. RNA sequencing is performed to identify differentially expressed genes, which show that the expressions of proliferation and migration-associated genes are inhibited, while the apoptosis and immune response gene expressions are upregulated after the synergistic treatments. This multifunctional nanoplatform that responds to the TME to realize the on-demand payload release and enhance PDT induced by TME modulation holds great promise for clinical applications in tumor therapy.

Physical Dissolution Combined with Photodynamic Depletion: A Two-Pronged Nanoapproach for Deoxygenation-Driven and Hypoxia-Activated Prodrug Therapy.

Hypoxia may enhance the chemoresistance of cancer cells and can significantly compromise the effectiveness of chemotherapy. Many efforts have been made to relieve or reverse hypoxia by introducing more oxygen into the tumor microenvironment (TME). Acting in a diametrically opposite way, in the current study, a novel nanocarrier was designed to further exhaust the oxygen level of the hypoxic TME. By creating such an oxygen depleted TME, the hypoxia-selective cytotoxin can work effectively, and oxygen exhaustion triggered chemotherapy can be achieved. Herein, deoxygenation agent, FDA-approved perfluorocarbon (PFC) and photosensitizer indocyanine green (ICG) for oxygen depletion, along with the hypoxia-activating drug tirapazamine (TPZ), were coincorporated within the poly(lactic-co-glycolic acid) (PLGA) nanoemulsion (ICG/TPZ@PPs) for the treatment of hypoxic tumors. Following hypoxia amplifying through physical oxygen dissolution and photodynamic depletion in tumors, hypoxic chemotherapy could be effectively activated to improve multitreatment synergy. After achieving local tumor enrichment, PFC-mediated oxygen dissolution combined with further ICG-mediated photodynamic therapy (PDT) under near-infrared (NIR) laser irradiation could induce enhanced hypoxia, which would activate the antitumor activity of codelivered TPZ to synergize cytotoxicity. Remarkably, in vivo experimental results exhibited that deoxygenated ICG/TPZ@PPs-based photothermal therapy (PTT), PDT, and hypoxia activated chemotherapy have an excellent synergistic ablation of tumors without obvious side effects, and therefore, a broad prospect of application of this nanocarrier could be expected.

Increased radiosensitivity of melanoma cells through cold plasma pretreatment mediated by ICG.

Radiation therapy (RT) is the primary treatment for many cancers, but its effectiveness is reduced due to radioresistance and side effects. The study aims to investigate an emerging treatment for cancer, cold atmospheric plasma (CAP), as a selectable treatment between cancerous and healthy cells and its role in the occurrence of photodynamic therapy (PDT) utilizing indocyanine green (ICG) as a photosensitizer. We examined whether the efficiency of radiotherapy could be improved by combining CAP with ICG. The PDT effect induced by cold plasma irradiation and the radiosensitivity of ICG were investigated on DFW and HFF cell lines. Then, for combined treatment, ICG was introduced to the cells and treated with radiotherapy, followed by cold plasma treatment simultaneously and 24-h intervals. MTT and colony assays were used to determine the survival of treated cells, and flow cytometry was used to identify apoptotic cells. Despite a decrease in the survival of melanoma cells in CAP, ICG did not affect RT. Comparing the ICG + CAP group with CAP, a significant reduction in cell survival was observed, confirming the photodynamic properties of plasma utilizing ICG. The treatment outcome depends on the duration of CAP. The results for healthy and cancer cells also confirmed the selectivity of plasma function. Moreover, cold plasma sensitized melanoma cells to radiotherapy, increasing treatment efficiency. Treatment of CAP with RT can be effective in treating melanoma. The inclusion of ICG results in plasma treatment enhancement. These findings help to select an optimal strategy for a combination of plasma and radiotherapy.

Simultaneous Imaging and Photodynamic-Enhanced Photothermal Inhibition of Cancer Cells Using a Multifunctional System Combining Indocyanine Green and Polydopamine-Preloaded Upconversion Luminescent Nanoparticles.

This work introduces a novel multifunctional system called UPIPF (upconversion-polydopamine-indocyanine-polyethylene-folic) for upconversion luminescent (UCL) imaging of cancer cells using near-infrared (NIR) illumination. The system demonstrates efficient inhibition of human hepatoma (HepG2) cancer cells through a combination of NIR-triggered photodynamic therapy (PDT) and enhanced photothermal therapy (PTT). Initially, upconversion nanoparticles (UCNP) are synthesized using a simple thermal decomposition method. To improve their biocompatibility and aqueous dispersibility, polydopamine (PDA) is introduced to the UCNP via a ligand exchange technique. Indocyanine green (ICG) molecules are electrostatically attached to the surface of the UCNP-polydopamine (UCNP@PDAs) complex to enhance the PDT and PTT effects. Moreover, polyethylene glycol (PEG)-modified folic acid (FA) is incorporated into the UCNP-polydopamine-indocyanine-green (UCNP@PDA-ICGs) nanoparticles to enhance their targeting capability against cancer cells. The excellent UCL properties of these UCNP enable the final UCNP@PDA-ICG-PEG-FA nanoparticles (referred to as UPIPF) to serve as a potential candidate for efficient anticancer drug delivery, real-time imaging, and early diagnosis of cancer cells. Furthermore, the UPIPF system exhibits PDT-assisted PTT effects, providing a convenient approach for efficient cancer cell inhibition (more than 99% of cells are killed). The prepared UPIPF system shows promise for early diagnosis and simultaneous treatment of malignant cancers.

Development of superior nanotheranostic agents with indocyanine green-conjugated poly(styrene-alt-maleic acid) nanoparticles for tumor imaging and phototherapy.

Developing safe, high-quality theranostic agents for cancer treatment is of great clinical value. In this work, for the first time, the clinical indocyanine green (ICG) is coupled with the biocompatible poly(styrene-alt-maleic anhydride) (PSMAn) to obtain the PSMAn-ICG polymer. The self-assembly of its hydrolyzed product in water results in ICG-conjugated poly(styrene-alt-maleic acid) nanoparticles (PSMA-ICG NPs). Intriguingly, the NPs have many advantages, including good solubility and stability in aqueous solutions, high photostability and decreased hemolytic damage to red blood cells, highlighting the importance of PSMA coupling. More interestingly, PSMA-ICG NPs significantly promote tumor targeting and enable long-term imaging of tumors. Furthermore, the administration of PSMA-ICG NPs in combination with near-infrared laser irradiation provides superior potency in the photothermal therapy of tumors. Furthermore, 9-amino-sialic acid (Sia)-coated PSMA-ICG NPs are fabricated, further enhancing tumor imaging and phototherapy. This is the first report of PSMA-NIR conjugates achieving tumor reduction in mice. Overall, this study provides novel phototheranostic agents with broad clinical transformation prospects.

Clinical Study of Antimicrobial Efficacy of Laser Ablation Therapy with Indocyanine Green in Root Canal Treatment.

INTRODUCTION: Laser ablation (LA) therapy is used as an adjunct to endodontic treatment to improve microbial reduction. However, studies evaluating the impact of LA with indocyanine green (ICG) are scarce. This study aimed to evaluate the antimicrobial efficacy of LA therapy with ICG in root canal treatment. METHODS: Sixty patients with periapical lesions in teeth with a single canal and absence of pain, edema, and previous treatment were selected. Patients were randomly allocated into 3 groups according to the apical sizes used (n = 20); 25/04, 30/04, and 35/04 were the final sizes used. In half the patients of each group, 2.5% sodium hypochlorite was used as an irrigating solution, and in the other half, saline solution was used. After instrumentation, all patients received LA therapy with ICG. Root canal sampling was performed before (S1) and after (S2) root canal instrumentation and immediately after LA therapy with ICG (S3). Colony-forming units were counted, and statistical tests were applied (P < .05). RESULTS: There was a significant reduction in colony-forming units from S1 to S2 in all treatment protocols (P < .05); 2.5% sodium hypochlorite as an irrigating solution showed a greater microbial reduction compared with saline solution (P < .05). LA therapy with ICG further reduced the microbial counts significantly (S2 to S3 and S1 to S3) whether sodium hypochlorite or saline was used (P < .05). CONCLUSIONS: LA therapy with ICG significantly increased microbial reduction in root canals regardless of instrumentation sizes or the irrigation solution used.

Analgesic and potentiated photothermal therapy with ropivacaine-loaded hydrogels.

Rationale: Tumor ablation can cause severe pain to patients, but there is no satisfactory means of analgesia available. In addition, recurrence of residual tumors due to incomplete ablation threatens patient safety. Photothermal therapy (PTT), a promising approach for tumor ablation, also faces the aforementioned problems. Therefore, developing novel photothermal agents that can efficiently relieve PTT-associated pain and potentiate the PTT efficacy are urgently needed. Methods: The Pluronic F127 hydrogel doped with indocyanine green (ICG) was served as photothermal agent for PTT. Mouse model that inoculation of tumor near the sciatic nerve was constructed to assess the PTT-evoked pain. Subcutaneous and sciatic nerve vicinal tumor-bearing mice were used to test the efficacy of PTT. Results: PTT-evoked pain depends on an increase in tumor temperature and is accompanied by the activation of TRPV1. A simple introduction of local anesthetic (LA) ropivacaine into ICG-loaded hydrogels relieves PTT-induced pain and exerts long-lasting analgesia compared with opioid analgesia. More interestingly, ropivacaine upregulates major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-doped with ropivacaine, TLR7 agonist imiquimod and ICG was rationally designed. In the hydrogel system, imiquimod primes tumor-specific CD8+ T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8+ T cells through upregulating MHC-I. Consequently, the hydrogel maximumly increases CD8+ T cells infiltration into tumor and potentiates PTT efficacy. Conclusion: This study for the first time provides an LA-dopped photothermal agents for painless PTT and innovatively proposes that a LA can be used as an immunomodulator to potentiate the PTT efficacy.

Relationship between macular intervortex vein anastomosis and optical coherence tomography biomarkers in chronic central serous chorioretinopathy.

BACKGROUNDS: To evaluate the optical coherence tomography (OCT) biomarkers of patients with central serous chorioretinopathy (CSC) according to the presence or absence of direct anatomical relation to intervortex vein anastomosis (IVA) on indocyanine green angiography. METHODS: We reviewed the records of 39 patients with chronic CSC. Patients were categorized in 2 groups: presence of IVA(Group A) or absence of IVA(Group B) in the macular region. Localization of IVA was categorized in 3 areas according to ETDRS grid:inner 1 mm circle (area-1), 1-3 mm middle circle (area-2) and 3-6 mm outer circle (area-3). RESULTS: There were 31 eyes in Group A,21 eyes in Group B. Mean age of the patients was 52.5 ± 11.3years in Group A,47.2 ± 11years in Group B(p<0.001).Mean initial visual acuity (VA) was 0.38±0.38LogMAR in Group A, 0.19±0.21LogMAR in Group B(p<0.001).Mean subfoveal choroidal thickness(SFCT) was 436.3 ± 134.3µ in Group A,480.2 ± 136.6µ in Group B(p<0.001).Localization of IVA in area-1 was correlated with inner choroidal attenuation (ICA) and leakage on IVA(p = 0.011,p = 0.02). Localization of IVA in area-3 was correlated with irregular lesions on RPE(p = 0.042).Smokestack configuration,intraretinal cysts and ICA were correlated with worse initial VA(p<0.001,p = 0.001 and p = 0.04).Shaggy subtype of photoreceptor disruption was associated with better initial VA(p = 0.003). CONCLUSIONS: We detected older age, worse initial VA and thinner SFCT in patients with chronic CSC and macular region IVA(m-IVA). Long term follow-up of patients with and without m-IVA may exhibit the difference in treatment outcomes and development of neovasculopathy.

Adjunctive effects of photodynamic therapy using indocyanine green in residual pockets during periodontal maintenance therapy: A split-mouth randomized controlled trial.

BACKGROUND: Prospective studies have reported conflicting results regarding the adjunctive effect of antimicrobial photodynamic therapy (aPDT) on clinical and microbiological parameters in individuals under periodontal maintenance therapy (PMT). This study aimed to evaluate the clinical and microbiological adjunctive effects of aPDT using indocyanine green (ICG) in residual sites with probing depth (PD) ≥5 mm during PMT in comparison with scaling and root planing (SRP) alone. METHODS: A split-mouth randomized controlled clinical trial was conducted with 24 individuals in a PMT program. Contralateral quadrants with eligible residual sites were randomly assigned to either SRP + aPDT (test group) or SRP alone (control). aPDT included ICG dye and diode laser (909 nm) performed together with SRP and repeated 15 days after. Periodontal clinical parameters, periodontal inflamed surface area (PISA) index, and subgingival biofilm samples were collected at baseline (T1), 3 (T2), and 6 months later (T3). Microbiological analyses were performed by quantitative real-time polymerase chain reaction. RESULTS: Significant improvements were observed in all clinical and microbiological parameters in both groups from T1 to T3. However, no significant differences were observed regarding plaque index, PD, and clinical attachment level. Test group showed significantly greater reductions in bleeding on probing (BOP), PISA index, and Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans levels, when compared with controls. CONCLUSIONS: Both treatments resulted in significant clinical periodontal improvements, but with no significant differences between groups except from inflammation parameters. aPDT using ICG resulted in significant reductions in BOP and PISA index, as well as in P. gingivalis and A. actinomycetemcomitans levels.

Calcium-peroxide-mediated cascades of oxygen production and glutathione consumption induced efficient photodynamic and photothermal synergistic therapy.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are potent approaches to cancer treatment. However, the tumor microenvironment (TME) characterized by severe hypoxia and abundant glutathione (GSH) significantly reduces the effectiveness of PDT. In this study, we developed an oxidative stress amplifier CaO2/ICG@ZIF-8, which was capable of self-sufficient O2 delivery and GSH depletion to enhance PDT and PTT synergistic therapy. We utilized ZIF-8 as nanocarriers that when loaded with CaO2 and indocyanine green (ICG) form CaO2/ICG@ZIF-8 nanoparticles, which exhibit a uniform particle size distribution and a hydrated particle size of about 215 nm. CaO2 reacts with water under acidic conditions to produce O2 so CaO2/ICG@ZIF-8 has an excellent O2 supply capacity, which is essential for PDT. Moreover, CaO2/ICG@ZIF-8 also reacts with GSH to form glutathione disulfides (GSSH), enhancing the therapeutic outcome of PDT by preventing the consumption of local ractive oxygen species. Beyond that, CaO2/ICG@ZIF-8 can produce strong hyperthermia with a photothermal conversion efficiency of about 44%, which is exceedingly appropriate for PTT. Owing to its augmentation, PTT/PDT mediated by CaO2/ICG@ZIF-8 demonstrates intense tumor inhibitory effects in both in vitro and in vivo studies. Notably, the Zn and Ca generated by CaO2/ICG@ZIF-8 degradation are essential elements for the body, so CaO2/ICG@ZIF-8 shows favorable safety. Altogether, the research provides a promising PDT/PTT synergistic therapeutic strategy for cancer and may show more medical applications in the future.

Microfluidic Generation of Near-Infrared Photothermal Vitexin/ICG Liposome with Amplified Photodynamic Therapy.

Glioma, in which a malignant tumor cell occurs in neural mesenchymal cells, has a rapid progression and poor prognosis, which is still far from desirable in clinical treatments. We developed a lab-on-a-chip (LOC) device for the rapid and efficient preparation of vitexin/indocyanine green (ICG) liposomes. Vitexin could be released from liposome to kill cancer cell, which can potentially improve the glioma therapeutic effect and reduce the treatment time through synergistic photodynamic/photothermal therapies (PDT/PTT). The vitexin/ICG liposome was fabricated via LOC and its physicochemical property and release in vitro were evaluated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and live/dead staining were used to examine the enhanced antitumor effect of vitexin/ICG liposome in cooperation with PDT/PTT, while the related mechanism was explored by flow cytometry and western blot. The results were as follows: (1) The prepared vitexin/ICG liposome was smaller in size, homogenous in particle size distribution with significant low polydispersity index (PDI), and enhanced cumulative release in vitro. (2) We found that the formulated liposome presented strong cancer cell inhibition and suppression of its migration in a dose-dependent manner. (3) Further mechanistic studies showed that liposome combined with near-infrared irradiation could significantly upregulate levels of B cell lymphoma 2-associated X (Bax) protein and decrease B cell lymphoma 2 (Bcl-2) at protein levels. The vitexin/ICG liposomes prepared based on a simple LOC platform can effectively enhance the solubility of insoluble drugs, and the combined effect of PTT/PDT can effectively increase their antitumor effect, which provides a simple and valid method for the clinical translation of liposomes.