Coadministration of Quercetin and Indocyanine Green via PEGylated Phospholipid Micelles for Augmented Chem-Photothermal Combination Tumor Therapy.

A significant impediment persists in developing multicomponent nanomedicines designed to dismantle the heat shock protein (HSP)-based protective mechanism of malignant tumors during photothermal therapy. Herein, well-defined PEGylated phospholipid micelles were utilized to coencapsulate quercetin (QUE, a natural anticancer agent and potent HSP inhibitor) and indocyanine green (ICG, a photothermal agent) with the aim of achieving synchronized and synergistic drug effects. The subsequent investigations validated that the tailored micellar system effectively enhanced QUE's water solubility and augmented its cellular internalization efficiency. Intriguingly, the compositional PEGylated phospholipids induced extraordinary endoplasmic reticulum stress, thereby sensitizing the tumor cells to QUE. Furthermore, QUE played a crucial role in inhibiting the stress-induced overexpression of HSP70, thereby augmenting the photothermal efficacy of ICG. In systemic applications, the proposed nanotherapeutics exhibited preferential accumulation within tumors and exerted notable tumoricidal effects against 4T1 xenograft tumors under 808 nm near-infrared irradiation, facilitated by prominent near-infrared fluorescence imaging-guided chemo-photothermal therapy. Therefore, our strategy for fabricating multicomponent nanomedicines emerges as a coordinated platform for optimizing antitumor therapeutic efficacy and offers valuable insights for diverse therapeutic modalities.

Blood flow assessment of gastric tube with indocyanine green fluorescence angiography and postoperative endoscopy during esophagectomy: indocyanine green enhancement time indicated congestion.

BACKGROUND: During esophagectomy, evaluation of blood supply to the gastric tube is critically important to estimate and avoid anastomotic complications. This retrospective study investigated the relationship between indocyanine green (ICG) fluorescence angiography during esophagectomy and postoperative endoscopy findings, especially mucosal color change. METHODS: This study retrospectively collected data from 86 patients who underwent subtotal esophagectomy and reconstruction using a gastric tube for esophageal cancer at the Tokyo Medical and Dental University between 2017 and 2020. The flow speed of ICG fluorescence in the gastric tube was evaluated during the operation. Additionally, the main root of ICG enhancement and pattern of ICG distribution in the gastric tube were evaluated. On postoperative day 1 (POD1), the change in the mucosal color to white, thought to reflect ischemia, or black, thought to reflect congestion of the proximal gastric tube, was evaluated. The correlations between these factors, clinical parameters, and surgical outcomes were evaluated. Univariate and multivariate analyses used logistic regression to identify the risk factors affecting mucosal color change. RESULTS: Multivariate analyses revealed that the only independent significant predictor of mucosal congestion on POD1 was the ICG enhancement time of the right gastric tube tip (odds ratio, 14.49; 95% confidential interval, 2.41-87.24; P = 0.004). CONCLUSIONS: This study indicated that the ICG enhancement time is related to venous malperfusion and congestion rather than arterial malperfusion and ischemia.

Targeted blood-brain barrier penetration and precise imaging of infiltrative glioblastoma margins using hybrid cell membrane-coated ICG liposomes.

Surgical resection remains the primary treatment modality for glioblastoma (GBM); however, the infiltrative nature of GBM margins complicates achieving complete tumor removal. Additionally, the blood-brain barrier (BBB) poses a formidable challenge to effective probe delivery, thereby hindering precise imaging-guided surgery. Here, we introduce hybrid cell membrane-coated indocyanine green (ICG) liposomes (HM-Lipo-ICG) as biomimetic near-infrared (NIR) fluorescent probes for targeted BBB penetration and accurate delineation of infiltrative GBM margins. HM-Lipo-ICG encapsulates clinically approved ICG within its core and utilizes a hybrid cell membrane exterior, enabling specific targeting and enhanced BBB permeation. Quantitative assessments demonstrate that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes. Mechanistically, CD44 receptor-mediated endocytosis facilitates BBB translocation of HM-Lipo-ICG. Furthermore, HM-Lipo-ICG enables high-contrast NIR imaging, achieving a signal-to-background ratio of 6.5 in GBM regions of an orthotopic glioma mouse model, thereby improving tumor margin detection accuracy fourfold (84.4% vs. 22.7%) compared to conventional ICG liposomes. Application of HM-Lipo-ICG facilitates fluorescence-guided precision surgery, resulting in complete resection of GBM cells. This study underscores the potential of hybrid cell membrane-coated liposomal probes in precisely visualizing and treating infiltrative GBM margins.

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.

Indocyanine Green-Assisted Retrograde Ureterolysis in Robotic Transvaginal NOTES for the Management of Stage IV Endometriosis with Obliterated Cul-de-sac.

STUDY OBJECTIVE: To explore the use of indocyanine green (ICG) in highlighting ureteral anatomical landmarks for the successful and safe execution of robotic-assisted transvaginal NOTES hysterectomy with resection of deeply infiltrated endometriosis. DESIGN: Stepwise demonstration with narrated video footage. SETTING: An academic tertiary care hospital. Our patient is a 38-year-old G4P1031 with a symptomatic enlarged uterus secondary to adenomyosis and uterine myomas, dense adhesions between the posterior uterus, and left uterosacral ligament. INTERVENTIONS: Stage IV endometriosis with obliterated cul-de-sac is a challenging procedure in the surgical management of endometriosis. Ureterolysis is the key step to performing this surgery successfully and safely; however, the routine dissection of ureters from the sacral promontory level to the uterine artery is challenging in obliterated cul-de-sacs with pelvic side wall adhesions with the proximal ureter at greatest risk [1-4]. Using the ICG firefly technique allowed us to rapidly identify and safely dissect the ureter through robotic transabdominal endometriosis surgery [5,6]. The angle of approach in transvaginal NOTES surgery for hysterectomy with obliterated cul-de-sac endometriosis leads to far more difficulty in identifying the ureter at the beginning of surgery [3]. Therefore, an obliterated cul-de-sac was associated with a potentially increased risk of ureteral injury and bowel injury. We used ICG to help identify the ureter at the beginning of the case leading to reducing the risk of surgical complication, in which the concept of ureterolysis from the level of the uterine artery to the bifurcation of common iliac vessels in vNOTES surgery will be referred to as "vNOTES retrograde ureterolysis." With the cystoscope in place, a ureteral catheter was inserted into the right ureter and 5 cc of ICG was injected, and the same procedure was done on the left [1,5]. Bovie electrosurgical device was used to incise circumferentially around the cervix. The bladder was dissected off the pubovesical cervical fascia anteriorly and posteriorly with a combination of the Bovie as well as blunt and sharp dissection. Bilateral uterosacral and cardinal ligaments, as well as uterine arteries, were then clamped, transected with Mayo scissors, and secured. Entry into the anterior cul-de-sac was completed, and a stitch using 0 vicryl was used to tag the anterior peritoneum to the anterior vaginal cuff. Posterior entry was attempted unsuccessfully. The Gelpoint mini device was then placed, and the Da Vinci XI robot was docked. Bilateral ureters were identified and dissected out of bilateral pelvic sidewalls using the firefly mode at the level of the uterine artery. The ureters were easily dissected away from the uterus. The left broad ligament was then cauterized and transected using the vessel sealer. The plane between the uterus and the rectum was identified laterally, and the rectum was taken down from the uterus from the right to the left side. Bilateral broad ligaments were then cauterized and transected using the vessel sealer, followed by cauterization and transection of the round ligaments, utero-ovarian ligaments, and mesosalpinx bilaterally. The vaginal cuff angles were secured with a figure-of-eight stitch of 0 vicryl, and the vaginal cuff was then closed in a running fashion with 0 V-Loc. The patient was discharged in one day with reports of minimal pain (Videos 1-3). CONCLUSION: Robotic-assisted NOTES hysterectomy with deeply infiltrated endometriosis resection is feasible and safe with ICG-assisted ureteral labeling in a case of obliterated cul-de-sac. The unique green color labeling of ureters offers a prominent landmark in assisting the ureteral dissection while avoiding ureteral and bowel injury, resulting in the possibility of using vNOTES surgery in challenging cases.

Original and liposome-modified indocyanine green-assisted fluorescence study with animal models.

Medical diagnosis heavily relies on the use of bio-imaging techniques. One such technique is the use of ICG-based biological sensors for fluorescence imaging. In this study, we aimed to improve the fluorescence signals of ICG-based biological sensors by incorporating liposome-modified ICG. The results from dynamic light scattering and transmission electron microscopy showed that MLM-ICG was successfully fabricated with a liposome diameter of 100-300 nm. Fluorescence spectroscopy showed that MLM-ICG had the best properties among the three samples (Blank ICG, LM-ICG, and MLM-ICG), as samples immersed in MLM-ICG solution achieved the highest fluorescence intensity. The NIR camera imaging also showed a similar result. For the rat model, the best period for fluorescence tests was between 10 min and 4 h, where most organs reached their maximum fluorescence intensity except for the liver, which continued to rise. After 24 h, ICG was excreted from the rat's body. The study also analyzed the spectra properties of different rat organs, including peak intensity, peak wavelength, and FWHM. In conclusion, the use of liposome-modified ICG provides a safe and optimized optical agent, which is more stable and efficient than non-modified ICG. Incorporating liposome-modified ICG in fluorescence spectroscopy could be an effective way to develop novel biosensors for disease diagnosis.

Clinical and microbiological efficacy of indocyanine green-based antimicrobial photodynamic therapy as an adjunct to non-surgical treatment of periodontitis: a randomized controlled clinical trial.

OBJECTIVES: The aim of the present randomized clinical trial (RCT) with a parallel arm design was to evaluate the clinical and microbiological efficacy of repeated ICG-aPDT as an adjunct to full-mouth subgingival debridement in the treatment of periodontitis. MATERIALS AND METHODS: Twenty-four periodontitis patients were treated with full-mouth ultrasonic subgingival debridement (FMUD). Initial sites with probing depth (PD) > 4 mm were randomly assigned to receive the test (ICG-aPDT with an 810 nm diode laser) or the control treatment (off-mode aPDT) one and four weeks after FMUD. Clinical parameters were registered after 3 and 6 months. The presence of the main periodontal pathogens in subgingival samples was assessed with real-time PCR. RESULTS: Both treatment modalities resulted in significant clinical improvements at 3 and 6 months. The only significant differences in favour of the test group were found at 6 months for a higher PD reduction in initial deep pockets (PD ≥ 6 mm) and a higher percentage of closed pockets (PD ≤ 4 mm/no bleeding on probing). Limited microbiological changes were observed in both groups after treatment with no inter-group difference, except for a more significant reduction in Aggregatibacter actinomycetemcomitans and Parvimonas micra levels in the test group at 3 months. CONCLUSION: The combination of repeated ICG-aPDT and FMUD provided no benefits except for selective clinical and microbiological improvements compared to FMUD alone. CLINICAL RELEVANCE: Based on the obtained results, only limited adjunctive effects could be found for the combined use of ICG-aPDT and FMUD. Further, well-designed RCT with larger sample sizes are required to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04671394.

The effect of antimicrobial photodynamic therapy on periodontal disease and glycemic control in patients with type 2 diabetes mellitus.

OBJECTIVES: This study is aimed at determining the effect of concomitant antimicrobial photodynamic therapy (aPTD) on periodontal disease and glycaemic control in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Twenty-four patients with T2DM were enrolled in the study. Periodontal clinical parameters were assessed by measuring probing pocket depth (PPD), clinical attachment loss (CAL), gingival recession (GR), full-mouth bleeding score (FMBS), full-mouth plaque score (FMPS), and full-mouth sulcus bleeding score (FMSBS). Glycated haemoglobin A1c (HbA1c) was measured. To determine the presence of the following periodontal pathogenic bacteria, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, subgingival plaque samples were taken from two periodontal pockets per jaw with the greatest PPD using paper tips. Patients were randomly divided into the test and control group. In the test group, full-mouth disinfection was performed in combination with aPTD. In the control group, only full-mouth disinfection was performed. RESULTS: The results showed an improvement in periodontal clinical parameters in both groups. The difference between the groups in favour of the test group was statistically significant for BOP. The HbA1c level decreased in both groups. The difference was not statistically significant. The results of the microbiological analysis suggest that the presence of periodontal pathogenic bacteria is lower with additional antimicrobial photodynamic therapy with statistically significant difference for T. forsythia. CONCLUSIONS: Additional aPDT causes a significant reduction in BoP in the proportion of positive sites for periodontal pathogens. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05816941. CLINICAL RELEVANCE: aPTD is a noninvasive adjunctive therapy that can positively influence the periodontal treatment outcome.

Semi-Permanent Use of Indocyanine Green Latex Phantom for Fluorescence Emission.

INTRODUCTION: Testing the fluorescence emission of the vascular circulation status of the indocyanine green (ICG) fluorescence contrast agent to validate the system performance is crucial. Hence, the development of an ICG phantom is imperative, and this study proposes a method for manufacturing an ICG phantom. METHOD: The ICG with an initial concentration was subjected to 0.2 cc sampling through syringe(x), and an ICG (0.2 cc) is diluted with silicon (Si) latex lubber (10 mL) during the manufactured the phantom. The brightest fluorescence expression state is 30 µM, and if it exceeded 50 µM, fluorescence fading occurred and changed to a dark color. RESULTS: The liquid (ICG) of the concentration range is 0.003 mM to 0.24 mM, and the maximum fluorescence expression range is 0.005 to 0.006 mM when the phantom is irradiated using a 780-nm (800 mW) LED. In addition, the fluorescence emission is reduced to 0.24 mM, and the fluorescence expression concentration is 10 µM, 30 µM, and 50 µM, respectively. The decreasing of the fluorescence emission is beginning to 50 µM. CONCLUSIONS: In this study, the proposed phantom with ICG fluorescence emission using latex lubber is proposed. In this works, the proposed phantom is improved the performance for ICG fluorescence emission. In the manufactured phantom, the phantom is used for gelatin, and the advance of phantom has easy manufacturing and long-life fluorescence emission (semipermanent) due to incorrodible material (latex lubber). To experimental results of a phantom, the ICG fluorescent contrast medium (0.055 mM) is same to 30 µM. Then, the 0.055 mM and 30 µM have high resolution and fluorescence emission status. Thus, the results are in good agreement.

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.

Nanostructure-Driven Indocyanine Green Dimerization Generates Ultra-Stable Phototheranostics Nanoparticles.

Indocyanine green (ICG) is the only near-infrared (NIR) dye approved for clinical use. Despite its versatility in photonic applications and potential for photothermal therapy, its photobleaching hinders its application. Here we discovered a nanostructure of dimeric ICG (Nano-dICG) generated by using ICG to stabilize nanoemulsions, after which ICG enabled complete dimerization on the nanoemulsion shell, followed by J-aggregation of ICG-dimer, resulting in a narrow, red-shifted (780 nm→894 nm) and intense (≈2-fold) absorbance. Compared to ICG, Nano-dICG demonstrated superior photothermal conversion (2-fold higher), significantly reduced photodegradation (-9.6 % vs. -46.3 %), and undiminished photothermal effect (7 vs. 2 cycles) under repeated irradiations, in addition to excellent colloidal and structural stabilities. Following intravenous injection, Nano-dICG enabled real-time tracking of its delivery to mouse tumors within 24 h by photoacoustic imaging at NIR wavelength (890 nm) distinct from the endogenous signal to guide effective photothermal therapy. The unprecedented finding of nanostructure-driven ICG dimerization leads to an ultra-stable phototheranostic platform.

Indocyanine Green Performance Enhanced System for Potent Photothermal Treatment of Bacterial Infection.

The instability in solution and aggregation-induced self-quenching of indocyanine green (ICG) have weakened its fluorescence and photothermal properties, thus inhibiting its application in practice. In this study, the cationic and anionic liposomes containing ICG were prepared based on 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-glycerol (DPPG), respectively. Molecular dynamics (MD) simulations demonstrate that ICG molecules are better distributed in the membranes of cationic DOTAP-based liposomes, leading to a superior fluorescence and photothermal performance. The liposomal ICG also shows the physical and photothermal stability during irradiation and long-term storage. On this basis, the prepared DOTAP-based liposomal ICG was encapsulated in the self-healing hydrogel formed by guar gum through the borate/diol interaction. The proposed liposomal ICG-loaded hydrogel can not only convert near-infrared (NIR) light into heat effectively but also repair itself without external assistance, which will realize potent photothermal therapy (PTT) against bacterial infection and provide the possibility for meeting the rapidly growing needs of modern medicine.

Examination of abdominal wall perfusion using varying suture techniques for midline abdominal laparotomy closure.

BACKGROUND: With a growing interest in the primary prevention of incisional hernias, it has been hypothesized that different suturing techniques may cause various levels of tissue ischemia. Using ICG laser-induced fluorescence angiography (ICG-FA), we studied the effect of different suture materials and closure techniques on abdominal wall perfusion. METHODS: Fifteen porcine subjects underwent midline laparotomy, bilateral skin flap creation, and three separate 7 cm midline fascial incisions. Animals underwent fascial closure with 5 different techniques: (1) Running 0-PDS® II (polydioxanone) Suture with large bites; (2) Running 0-PDS II Suture with small bites; (3) Interrupted figure-of-eight (8) PDS II Suture, (4) Running 0-barbed STRATAFIX™ Symmetric PDS™ Plus Knotless Tissue Control Device large bite; (5) Running 0-STRATAFIX Symmetric PDS Plus Device small bites. ICG-FA signal intensity was recorded prior to fascial incision (baseline), immediately following fascial closure (closure), and at one-week (1-week.). Post-mortem, the abdominal walls were analyzed for inflammation, neovascularity, and necrosis. RESULTS: PDS II Suture with small bites, fascial closure at the caudal 1/3 of the abdominal wall, and the 1-week time period were all independently associated with increased tissue perfusion. There was also a significant increase in tissue perfusion from closure to 1-week when using small bites PDS II Suture compared to PDS II Suture figure-of-8 (p < 0.001) and a trend towards significance when compared with large bites PDS II Suture (p = 0.056). Additionally, the change in perfusion from baseline to 1 week with small bites was higher than with figure of 8 (p = 0.002). Across all locations, small bite PDS II Suture has greater total inflammation than figure of 8 (p < 0.001). CONCLUSIONS: The results suggest that the small bite technique increases abdominal wall perfusion and ICG-FA technology can reliably map abdominal wall perfusion. This finding may help explain the reduced incisional hernia rates seen in clinical studies with the small bite closure technique.

Role of indocyanine green combined with radiotracer-Technetium 99 m in neck surgery for primary and recurrent head and neck cancer: preliminary results of a tertiary cancer center.

PURPOSE: Neck dissection (ND), whether therapeutic or elective, is an essential component of the treatment of head and neck squamous cell carcinoma (HNSCC). Due to altered anatomy and fibrosis caused by initial treatments, surgeons face challenges during salvage ND. A combination of Technetium-99 m and indocyanine green (ICG) previously used in the sentinel lymph node (SLN) biopsy for oral cavity cancers, may be useful in different types of neck surgeries. We aimed to show the additional advantage of this combination in detecting HNSCC and thyroid cancer recurrences, as well as individual lymphatic drainage in elective ND. METHODS: We retrospectively reviewed medical records of patients, underwent neck surgery guided with ICG and Tc-99 m, in Hacettepe University Hospital between June 2018 and December 2020. In a total of 28 patients, intraoperative gamma probes were paired with near infrared (NIR) cameras. Patients are divided into two groups: neck surgery with recurrent occult lesion localization (NS- ROLL) (n: 14) and ND with SLN screening (ND-SLNS) (n: 14). RESULTS: Among all 14 patients in NS-ROLL group, recurrent diseases, hidden behind tissues were 100% successfully localized. In ND-SLNS group, 238 lymph nodes were harvested, metastasis rate was 31.3% (10/32) in sentinel nodes. SLNS revealed 100% accuracy in detecting metastasis in clinically N0 neck (10/238). Contralateral lymphatic drainage was observed in three patients (lateral-sided oral cavity SCC). In two patients (floor of mouth), three sentinel nodes were detected by NIR only. CONCLUSION: The use of ICG-radiotracer provides additional value in disease removal for both primary and recurrent tumors of the head and neck.

Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy.

BACKGROUND: Cancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice. RESULTS: Herein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration. CONCLUSIONS: Our research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system.

Dynamic characterization of indocyanine green-assisted dental caries ablation with continuous diode laser using thermal imaging and fluorescence spectroscopy.

We describe the time-resolved thermal changes in indocyanine green (ICG)-assisted diode laser ablation of dental caries as a potential technique for painless treatment based on the selective photoabsorption and controlled photothermal ablation. Static ablation mode produced a higher temperature rise compared with scanning mode due to localized accumulation of heat. A temperature rise between 45-80 and 70-95 °C was obtained after 20 s that corresponded to 29 and 80 W cm-2, respectively. The temperature of the tooth surface increased by irradiation time, and it behaved linearly up to 70 °C at 29 and 80 W cm-2. A maximum ablation per area of about 0.3 and 0.45 mg cm-2 was achieved after 80 s exposure at 29 and 80 W cm-2, respectively. A statistically significant difference is observed in mean carious teeth weight at various exposure times between low and high irradiances. A thermal penetration depth of 0.8-9 mm is determined for 1-100 s of exposure time. The IR thermal imaging of ICG temperature as a function of exposure time showed a linear increase for 60 s beyond which it deviated. The laser-induced fluorescence spectroscopy indicated that the ICG quality can be altered during the course of irradiation, which in our case, it corresponded to ≈ 78% loss of signal within 23 min of exposure. The caries removal experiment was performed within 100 s corresponding to ≈ 7% loss. We believe that the application of the above-combined technique can be utilized as a monitoring device to control the ablation interaction process.

Efficacy of antimicrobial photodynamic therapy (aPDT) for nonsurgical treatment of periodontal disease: a systematic review.

Although the standard treatment for periodontal disease is based on scaling and root planing (SRP), the use of antimicrobial photodynamic therapy (aPDT) has been studied as a complement to obtain better clinical results. The purpose of this study was to evaluate the effect of aPDT as adjuncts to SRP, compared with SRP alone, on clinical parameters of chronic periodontal patients. Only randomized controlled trials with at least 3-month follow-ups, of SRP alone and in association with aPDT, were included. The MEDLINE (PubMed), Google Scholar, and LILACS databases were searched for articles published up to July 2020. Random-effects meta-analyses were conducted for clinical attachment level (CAL) and probing pocket depth (PPD) change after treatment. Of 141 potentially relevant papers, 22 were included. The association between SRP and aPDT promoted a significant CAL gain and PPD reduction. Periodontal treatment was partially improved by aPDT, and a favorable effect of indocyanine green-mediated aPDT was observed, and high concentrations of phenothiazine chloride presented clinical improvement as well.

Indocyanine green-mediated antimicrobial photodynamic therapy as an adjunct to periodontal therapy: a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis was to evaluate the efficacy of indocyanine green-mediated photodynamic therapy (ICG-PDT) as an adjunct to non-surgical periodontal therapy (NSPT), in the management of chronic periodontitis. MATERIALS AND METHODS: Four electronic databases (PubMed, Cochrane Central Register of Controlled Trials, Embase via OVID, Web of Science) were searched for randomised controlled trials comparing NSPT with ICG-PDT to NSPT without laser therapy. Primary outcome measures were changes in probing pocket depth (PPD) and clinical attachment level (CAL). Clinical outcomes were extracted and pooled from 7 eligible trials and meta-analyses conducted using mean difference with standard deviations. RESULTS: For PPD, adjunctive ICG-PDT resulted in a mean additional reduction of 1.17 mm (95% CI: 0.67-1.66 mm) at 3 months and a mean additional reduction of 1.06 mm (95% CI: 0.54-1.57 mm) at 6 months. For CAL, adjunctive ICG-PDT resulted in a mean additional gain of 0.70 mm (95% CI: 0.17-1.23 mm) at 3 months and a mean additional gain of 1.03 mm (95% CI: 0.83-1.24 mm) at 6 months. No adverse events were reported in any studies. CONCLUSIONS: The adjunctive use of ICG-PDT in NSPT results in improved treatment outcomes at 3 and 6 months post-therapy. Further investigation is needed to evaluate variables such as different photosensitiser concentrations and adjusting parameters associated with the light source. CLINICAL RELEVANCE: Indocyanine green-based photosensitisers may be a novel, clinically efficacious agent for use in the management of periodontitis.

Photodynamic Inactivation of an Endodontic Bacteria Using Diode Laser and Indocyanine Green-Loaded Nanosphere.

Apical periodontitis, an inflammatory lesion causing bone resorption around the apex of teeth, is treated by eradicating infectious bacteria from the root canal. However, it has a high recurrence rate and often requires retreatment. We investigated the bactericidal effect of antimicrobial photodynamic therapy (aPDT)/photodynamic antimicrobial chemotherapy (PACT) using indocyanine green (ICG)-loaded nanospheres coated with chitosan and a diode laser on a biofilm of Enterococcus faecalis, a pathogen of refractory apical periodontitis. Biofilm of E. faecalis was cultured in a porcine infected root canal model. ICG solution was injected into the root canal, which was then irradiated with a laser (810 nm wavelength) from outside the root canal. The bactericidal effect was evaluated by colony counts and scanning electron microscopy. The result of the colony counts showed a maximum 1.89 log reduction after irradiation at 2.1 W for 5 min. The temperature rise during aPDT/PACT was confirmed to be within a safe range. Furthermore, the light energy transmittance through the root was at a peak approximately 1 min after the start of irradiation, indicating that most of the ICG in the root canal was consumed. This study shows that aPDT/PACT can suppress E. faecalis in infected root canals with high efficiency.

Cyanine Dyes for Photo-Thermal Therapy: A Comparison of Synthetic Liposomes and Natural Erythrocyte-Based Carriers.

Cyanine fluorescent dyes are attractive diagnostic or therapeutic agents due to their excellent optical properties. However, in free form, their use in biological applications is limited due to the short circulation time, instability, and toxicity. Therefore, their encapsulation into nano-carriers might help overcome the above-mentioned issues. In addition to indocyanine green (ICG), which is clinically approved and therefore the most widely used fluorescent dye, we tested the structurally similar and cheaper alternative called IR-820. Both dyes were encapsulated into liposomes. However, due to the synthetic origin of liposomes, they can induce an immunogenic response. To address this challenge, we proposed to use erythrocyte membrane vesicles (EMVs) as "new era" nano-carriers for cyanine dyes. The optical properties of both dyes were investigated in different biological relevant media. Then, the temperature stability and photo-stability of dyes in free form and encapsulated into liposomes and EMVs were evaluated. Nano-carriers efficiently protected dyes from thermal degradation, as well as from photo-induced degradation. Finally, a hemotoxicity study revealed that EMVs seem less hemotoxic dye carriers than clinically approved liposomes. Herein, we showed that EMVs exhibit great potential as nano-carriers for dyes with improved stability and hemocompatibility without losing excellent optical properties.