Indocyanine Green-mediated Photodynamic Therapy Research Articles

Optimizing near infrared laser irradiation and photosensitizer accumulation period for indocyanine green-mediated photodynamic therapy in breast cancer xenografts: a focus on treatment and characterization.

Photodynamic therapy (PDT) is a promising cancer treatment approach. Indocyanine green (ICG) is a water-soluble tricarbocyanine dye with a peak absorption wavelength of around 800nm and possesses the capacity to produce reactive oxygen species. FTIR spectroscopy is rarely used and offers insights into molecular changes in cancer studies. MCF-7 cells were injected into Nude mouse. Once the tumor had grown to a size of 3-4mm, mice were randomized into the 12 PDT groups. After each mouse received 5mg/kg of ICG, they were photo-irradiated with a diode laser emitting light at 809nm, followed by waiting intervals of 0, 30, 60, and 90min. Laser irradiation parameters were 150, 250, 500 mW/cm2 and irradiation duration was 1200s. The tumor size was measured every day for four days. The FTIR spectroscopy was used to perform spectral analysis on tumor tissue samples. Four distinct regions (3600-2800cm-1, 1750-1550cm-1, 1540-1450cm-1, and 1700-1100cm-1) were analyzed, and Hierarchical Cluster study was carried out. A decrease in tumor volume was observed with all PDT applications, except, increases in tumor volume was observed at 150mW 90-minute group. PDT administered after 90min revealed variations in 150mW and 250mW laser powers in the 3600cm-1-2800cm-1 range. The 250mW and 500mW applications resulted in a considerable reduction in fibroadenoma and carcinoma tissues, according to an analysis comparing the A1695 / A1635 ratio. It is proposed that the ideal treatments for further investigation have a power output of 250 mW.

The effect of indocyanine green mediated photodynamic therapy on periodontal inflammatory markers among smokers versus non smokers

The effect of indocyanine green mediated photodynamic therapy on periodontal inflammatory markers among smokers versus non smokers

Antimicrobial effect of indocyanine green-mediated photodynamic therapy in patients with periodontal disease: A systematic review

Abstract Aim: This systematic review assessed the antimicrobial effect of indocyanine green-mediated photodynamic therapy (ICG-PDT) in patients with periodontal disease. Materials and Methods: Four electronic databases that is, MEDLINE, MEDLINE-In-Process, EMBASE, and Cochrane Library were systematically searched from their inception until December 22, 2022. Randomized controlled trials (RCTs) reporting the antimicrobial effect of ICG-PDT in patients with periodontal disease and published in English were included. The Cochrane risk of bias tool was used to assess the quality of the included RCTs. Two independent reviewers performed all the steps involved in a systematic review (primary and secondary screening, data extraction, and quality assessment). As the data extracted was not suitable for meta-analysis, the evidence was synthesized qualitatively. Results: Overall, seven RCTs from seven publications were included. All included studies had PDT, laser, or photothermal with ICG as the test group while the control group included low-level laser therapy, root surface debridement, and scaling and root planning. The bacterial species assessed across the included studies included Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Fusobacterium nucleatum, and Treponema denticola. With subtle exceptions, ICG-PDT in combination with root surface debridement and scaling and root planning significantly reduced the growth of periodontal pathogens from baseline. Conclusion: Based on the evidence from the limited studies, ICG-PDT seems to exhibit potent antimicrobial activity against an array of periodontal pathogens in patients with periodontal disease.

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

BackgroundKeloid, 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. MethodsIn 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. ResultsOur 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. ConclusionsThis 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.

Toxicity evaluation of indocyanine green mediated photodynamic therapy

BackgroundThe aim of the study is to determine the cytotoxic, genotoxic and inflammatory effects of indocyanine green (ICG) mediated photodynamic therapy (PDT) in direct contact with L-929 mouse fibroblast cells and over a dentin barrier. MethodsEight groups were evaluated; control (C), group with a dentin barrier (D), ICG applied directly on the cells (ICG), ICG applied over a dentin barrier (D-ICG), only laser applied (L), laser applied over a dentin barrier (D-L), ICG and laser applied directly on the cells (ICG-L), ICG and laser applied over a dentin barrier (D-ICG-L). Cell viability was evaluated via ATP Assay, DNA damage was evaluated via Comet Assay, and inflammatory markers IL-1β and TNF-α were assessed via ELISA test. ResultsCell viability decreased in group ICG (p<0.001). Cell viability decrease was higher in Group ICG-L (p<0.001). Cell viability decrease was lower in group D-ICG-L (p>0.05). Group L caused an increase in cell number (p<0.001). DNA damage was observed in ICG, D-ICG, and ICG-L groups (p<0.05). None of the groups displayed an increase of inflammatory markers IL-1β and TNF-α (p>0.05). ConclusionsThe presence of dentin between ICG and cells acted as a barrier and protected the cells. ICG-mediated PDT did not cause any cytotoxic, genotoxic or inflammatory effect. The use of ICG-mediated PDT for cavity disinfection is acceptable, but at this concentration its use in periodontal pocket disinfection is not recommended due to its cytotoxic and genotoxic properties.

In vitro study of the antibacterial effects of indocyanine green-mediated photodynamic therapy on Fusobacterium nucleatum biofilms

In vitro study of the antibacterial effects of indocyanine green-mediated photodynamic therapy on Fusobacterium nucleatum biofilms

Clinical Evaluation of the Effects of Topical Indocyanine-green Mediated Photosensitiser vs Aloe Vera Gel as Adjunct Therapy to Scaling and Root Planing in Chronic Periodontitis Patients.

To clinically evaluate and compare the efficacy of indocyanine green mediated photodynamic therapy (PDT) and aloe vera (AV) gel when used as adjunct therapy to scaling and root planing (SRP) for treatment of chronic periodontitis. One hundred fifty patients were randomly assigned to three treatment groups: group 1 (SRP), group 2 (SRP+PDT) and group 3 (SRP+AV). Four clinical parameters - plaque index (PI), bleeding on probing (BoP), periodontal (PD) pocket depth and clinical attachment level (CAL) - were evaluated at baseline and 3 and 6 months post treatment. Additionally, the amount of three inflammatory - cytokines IL-6, IL-8 and TNF-α - in gingival crevicular fluid (GCF) was identified using an enzyme-linked immune-sorbent assay (ELISA). Statistically significant improvement was observed for all clinical parameters in group 3 at follow-up in comparison to groups 1 and 2. Individuals treated with adjunct PDT showed statistically significant reduction in moderate (4-5 mm) and deep (≥6 mm) PD pockets at the 3-month follow-up. Group-2 and -3 patients displayed statistically significant reductions in cytokines IL-6, IL-8 and TNF-α at the 3-month follow-up in comparison to group 1 patients. This reduction in cytokines was maintained at the 6-month follow-up. Adjunct treatment regimens PDT and AV gel statistically significantly contributed to decreasing inflammation in periodontal tissue. AV /gel showed potential to decrease BoP, whereas PDT can facilitate increasing the clinical attachment level.

Clinical, bacterial, and inflammatory outcomes of indocyanine green-mediated photodynamic therapy for treating periimplantitis among diabetic patients: A randomized controlled clinical trial

Background This 6-months randomized controlled clinical trial aimed to assess the efficacy of indocyanine green mediated photodynamic therapy (ICG-PDT) as an adjunct to peri‑implant manual debridement (PIMD) versus PIMD alone among Diabetes Mellitus (DM) patients in the treatment of peri‑implantitis.Methods A total of 48 DM patients having 64 implants were treated with either ICG-PDT + PIMD (n = 35 implants) or PIMD alone (n = 29 implants). Clinical (probing depth [PD], bleeding on probing [BOP], and plaque index [PI]) and radiographic (peri‑implant crestal bone loss [PCBL]) peri‑implant variables were recorded. Bacterial species including Porphyromonas gingivalis and Treponema denticola were evaluated from peri‑implant plaque biofilms. Levels of interleukin (IL)-1β and IL-6 were assessed after the collection of peri‑implant sulcular fluid. All the evaluations were carried out at baseline, 3- and 6-months. The significance level was set to p < 0.05.Results All clinical parameters significantly reduced within both treatment groups (P<0.05). Intra-group comparison indicates that there was statistically significant reduction in PD and suppuration for ICG-PDT group (P<0.05). There was a statistically significant difference in the BOP between ICG-PDT and PIMD groups at both follow-up periods (P<0.001). However, there was a significant difference for PD (P = 0.001), suppuration (P = 0.01), and PCBL (P = 0.04) on 6 months follow-up between ICG-PDT and PIMD groups, respectively. Only ICG-PDT showed a significant reduction in P. gingivalis and T. denticola on both 3 months and 6 months follow-up compared to baseline. PIMD showed a statistically significant reduction only on 3 months follow-up compared to baseline. This reduction was maintained for both the species when dental implants were treated with ICG-PDT. However, PIMD failed to maintain this reduction until 6 months. Only at 3 months assessment that both treatment groups showed statistically significant reduction in IL-1β and IL-6 with no significant difference between the groups. Both biomarkers failed to maintain the reduction in both groups and significantly increased levels for IL-1β was noted at 6 months follow upConclusion Multiple application of indocyanine-green mediated photodynamic therapy resulted in improved clinical and microbial parameters among type 2 DM subjects in the treatment of peri‑implantitis.This clinical trial was registered in the ClinicalTrials.gov Protocol Registration and Results System with registration record number: NCT04833569

Indocyanine green\u2013mediated antimicrobial photodynamic therapy as an adjunct to periodontal therapy: a systematic review and meta-analysis

ObjectivesThe 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 methodsFour 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.ResultsFor 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.ConclusionsThe 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 relevanceIndocyanine green–based photosensitisers may be a novel, clinically efficacious agent for use in the management of periodontitis.

The effect of indocyanine green-mediated photodynamic therapy in healing of experimentally induced oral mucosal traumatic ulcer in rat.

Photodynamic therapy (PDT) is a promising approach for the healing of ulcerative lesions. This study aimed to investigate the effect of PDT using indocyanine green (ICG) in the healing of the experimentally induced oral mucosal traumatic ulcer in rat. Sixty adult male Sprague-Dawley rats were recruited in this experimental study. The ulceration was surgically made in the left cheek mucosa, and the rats were randomly assigned into four equal groups (n = 15). Oral ulcers in groups 1 and 2 were treated with the sterile saline solution (0.9%) and ICG (1mg/ml). In group 3, laser irradiation was applied using the 810nm diode laser in the continuous-wave mode for 30s (light dose: 55J/cm2, power: 300mW, spot size: 4.5mm). Following the topical application of ICG (1mg/ml) in group 4, laser irradiation was performed in the same way as the previous group. After 24h, treatments were repeated once more in all groups. The healing process was histopathologically assessed at the 3rd, 7th, and 14th days after ulceration. Wound healing was significantly accelerated in the ICG-mediated PDT group in comparison to the control group at all sampling time points (p < 0.005). However, the other groups displayed a similar healing rate (p > 0.05). Data suggest that ICG-mediated PDT has the potential to accelerate wound healing and prevent clinical infection in oral mucosal traumatic ulcers. However, further studies are required to confirm whether our results can be generalized to other wounds.

Antimicrobial efficacy of indocyanine green-mediated photodynamic therapy compared with Salvadora persica gel application in the treatment of moderate and deep pockets in periodontitis

In order to prove the idea that topical application of drugs can improve the clinical parameters affecting periodontal disease, a sound comparison should be made between topical therapeutic models. The aim of the present study was to assess the clinical efficacy of photodynamic therapy (PDT) and Salvadora persica (SP) gel as adjuncts to scaling and root planning (SRP) in the treatment of chronic periodontitis. The selected patients were divided into three groups, Group I (PDT + SRP), Group II (SP + SRP) and group III (SRP alone). Clinical inflammatory periodontal parameters including plaque index (PI), bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL) gain were assessed. Assessment of crevicular fluid interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) was performed using enzyme-linked immunosorbent assay technique. All measurements were recorded at baseline, 3 months and 6 months follow-up periods, respectively. A total of 73 patients completed the study. A significant improvement in the BOP was seen in Group II at both follow up visits when compared with other groups (p < 0.05). Only in Group-I that showed statistically significant reduction in moderate periodontal pockets at 3 months (p = 0.021), and significant reductions in deep pockets at 3-months (p = 0.003) and 6-months (p = 0.002), respectively. CAL gain also was reported to be seen in group-I at both visits (p < 0.05). Group- I and II significantly reduced the levels of IL-6 at 3-month period compared to Group-III. This reduction was further maintained by group-II and group-III at 6 months, respectively. TNF-α showed statistically significant decrease in Group II as compared to Group I and Group-III and this reduction was maintained by the end of 6-month visit (p = 0.045). Both the treatment modalities PDT and SP helped in reducing periodontal inflammation. PDT reported significant gain in clinical attachment level, whereas the SP significantly reduced the bleeding levels.

Topical colloidal indocyanine green-mediated photodynamic therapy for treatment of basal cell carcinoma

Indocyanine green (ICG) is a near-IR fluorescent dye with a great potential for application as photosensitizer in topical photodynamic therapy (PDT) of skin diseases. Despite its merits, its use has been hampered by its high degradation rate. Therefore, in the current article, ICG was encapsulated in a vesicular colloidal nanocarrier (transfersomes), with the aim of enhancing its therapeutic efficacy. Transfersomes were characterized for their entrapment efficiency, particle size, zeta potential, morphology, in vitro release and histopathological effect on mice skin. A pilot clinical study was conducted to test its therapeutic potential for PDT of basal cell carcinoma (BCC). Transfersomal ICG displayed particle size (∼125 nm) and a negative zeta potential (∼−31 mV). Transfersomes were also able to sustain the release of ICG >2 h. Upon incorporation of transfersomal ICG in gel form, it was found to maintain the normal histology of mice skin post-irradiation with diode laser 820 nm. Moreover, ICG transfersomal PDT achieved 80% clearance rate for BCC patients with minimal pain reported during treatment. The previous findings suggest that transfersomal nanoencapsulated ICG is a promising treatment modality for BCC.

The effect of indocyanine green-mediated photodynamic therapy as an adjunct to scaling and root planing in the treatment of chronic periodontitis: A comparative split-mouth randomized clinical trial.

The aim of this study was to assess the effect of adjunctive photodynamic therapy (PDT) (using 810 nm diode laser and Indocyanine green as photosensitizer) in chronic periodontitis. Patients with untreated chronic periodontitis were included. Treatment was done according to a split mouth design. All sites received periodontal treatment comprising scaling and root-planing (SRP). Test group were additionally treated with PDT. Plaque Index (PI), Gingival Index (GI), Probing Pocket Depth (PPD) and Relative Attachment Level (RAL) were evaluated at baseline, 1 month and 3 months. Mean baseline values for PI, GI, PPD and RAL were not different in the test group and control group. Statistical significant difference in PPD and RAL, 3 months after treatment was seen in test group as compared to the control group. In patients with chronic periodontitis, clinical outcomes of conventional SRP can be improved by adjunctive PDT.

Indocyanine green-mediated photodynamic therapy on glioblastoma cells in vitro

Photodynamic therapy (PDT) is an alternative therapy which is administered with non-toxic drugs, called photosensitizers (PSs) , along with irradiation at a specific wavelength of light to damage tumor cells. Different wavelengths of light sources and photosensitizers have been investigated in treatment of many cancer types. In this study, we investigated whether photodynamic therapy using indocyanine green (ICG), also a cyanine dye used in medical diagnostics, can be used to inhibit cell proliferation of glioblastoma. Glioblastoma cells were irradiated with a diode laser ( λ = 809 nm, 100 J cm −2 ) in continuous wave operation mode. Cell proliferation was measured by XTT assay at 24 h after light irradiation. While only ICG application (10 µg/ml and 50 µg/ml concentrations) had no effects on glioblastoma cell proliferation, ICG in combination with laser irradiation (ICG-PDT) caused a significant decrease of cell proliferation. In conclusion, ICG-PDT may be valuable therapeutic approach as potential treatment for cancer such as glioblastoma. The results could be used as primary data for efficacy of ICG-PDT on malignant tumors.

In-vitro efficacy of indocyanine green-mediated photodynamic therapy in combination with cisplatin or etoposide

Abstract:Localizing the cytotoxic effects of cancer therapies to only affect the tumor cells is a goal in oncology, to maximize efficacy and minimize treatment-related morbidities. Most effective chemotherapeutic drugs have significant side effects due to off-target toxicity. By comparison, photodynamic therapy (PDT) is a localized therapy without significant systemic toxicity but may have limited efficacy. Hence, combining PDT with chemotherapy was investigated to determine if the anti-tumor effect of the latter could be enhanced. PDT using indocyanine green (ICG), activated by near-infrared light, was investigated in lung tumor cells

The effects of combined treatment with ionizing radiation and indocyanine green-mediated photodynamic therapy on breast cancer cells

This study was undertaken to evaluate the effects of indocyanine green as a sensitizer in both photodynamic and radiation therapy on MCF-7 human breast cancer cells line. The cells were incubated with indocyanine green at different concentrations for 24h and were then exposed in the independent treatment groups to a non-coherent light at different fluence rates and X-ray ionizing radiation at different dose rates. In addition, combination effects of this chemo, photo, and radiotherapy were evaluated. The percentage of the cell survival was investigated using the MTT assay. The results showed that indocyanine green had no significant cytotoxic effects up to 100μM but as a photosensitizer had a strong cytotoxic effect on cancer cells. Despite, indocyanine green could not act as a radiosensitizer. Furthermore, it is surprising to find that 50μM of indocyanine green in combination with light at 60J/cm2 and 4Gy of X-ray radiation astonishingly killed cancer cells and reduced the percentage of viable cancer cells to be 3.42%. According to the findings, we observed the same efficacy of treatment by adding a low dose of radiation and reducing light fluence rate. In fact, it appears from our data that the adverse effects of photodynamic therapy can be partially abated without reducing the efficacy of treatment. Obviously, this new therapeutic avenue in breast cancer therapy could be worth further investigation and elucidation and should be tested in vivo models for being applied in human therapy.