Combination of a STING Agonist and Photothermal Therapy Using Chitosan Hydrogels for Cancer Immunotherapy.

Cyclic dinucleotides (CDNs) are a promising class of immune agonists that trigger the stimulator of interferon genes (STING) to activate both innate and acquired immunity. However, the efficacy of CDNs is limited by drug delivery barriers. Therefore, we developed a combined immunotherapy strategy based on injectable reactive oxygen species (ROS)-responsive hydrogels, which sustainably release 5,6-dimethylxanthenone-4-acetic acid (DMXAA) as known as a STING agonist and indocyanine green (ICG) by utilizing a high level of ROS in the tumor microenvironment (TME). The STING agonist combined with photothermal therapy (PTT) can improve the biological efficacy of DMXAA, transform the immunosuppressive TME into an immunogenic and tumoricidal microenvironment, and completely kill tumor cells. In addition, this bioreactive gel can effectively leverage local ROS to facilitate the release of immunotherapy drugs, thereby enhancing the efficacy of combination therapy, improving the TME, inhibiting tumor growth, inducing memory immunity, and protecting against tumor rechallenge.

Evaluation of the efficacy of triamcinolone acetonide in the treatment of keloids by high-frequency ultrasound.

BACKGROUND: Intralesional injection of triamcinolone acetonide is an effective method for treating keloids. It still lacks effective and objective evaluation methods. This study aimed to observe the efficacy of intralesional triamcinolone acetonide injections for the treatment of keloids and to explore the role of high-frequency ultrasound in the monitoring and evaluation of keloids therapy. METHODS: Fifty-one patients with keloids were treated with triamcinolone acetonide, once a week for 4 weeks. Lesions were detected, recorded, and evaluated using digital photography and high-frequency ultrasound before and after treatment. RESULTS: High-frequency ultrasound showed the depth of drug injection. After the last treatment, an average decrease in dermal tissue layer thickness of 39.0% is compared with before treatment. In addition, there are significant differences in the effectiveness of clinical assessments and ultrasound assessments of keloids with or without subjective symptoms. CONCLUSION: The observed results confirmed that intralesional injections of triamcinolone acetonide can effectively treat keloids. High-frequency ultrasound can be used as a therapeutic monitoring and therapeutic evaluation tool for intralesional injections of triamcinolone acetonide.

Effect of puerarin on melanogenesis in human melanocytes and vitiligo mouse models and the underlying mechanism.

Puerarin is the major bioactive ingredient derived from the root of the Pueraria lobata (Willd.), and its antioxidative stress effects have been demonstrated in several previous studies. Moreover, Puerarin can upregulate melanin synthesis and microphthalmia-associated transcription factor (MITF) transcription by increasing cAMP level of intracellular cyclic adenosine monophosphate. Vitiligo is an acquired cutaneous disorder of pigmentation, and the pathogenesis has remained elusive. Current treatment modalities are directed towards achieving repigmentation. In this study, we found that after treating with puerarin at various concentrations of 40 µmol/L, the melanin content of human melanocytes increased significantly and the apparent level of protein and the RNA levels of MITF, tyrosinase (TYR), and tyrosinase-related protein 1 (TRP-1) were also increased. Further, puerarin was shown to inhibit phosphorylation and activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) without significantly affecting p38 and c-Jun N-terminal kinase phosphorylation. These results demonstrated that puerarin stimulated melanogenesis in human melanocytes via inhibition of ERK1/2 signaling pathways, which leads to upregulation of MITF and TYR as well as TRP-1 subsequently. Additionally, mice vitiligo models with puerarin treatment showed lighter pathological changes. Therefore, we suggested that puerarin might be a potential medicine for vitiligo.

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.

The role of FOS-mediated autophagy activation in the indocyanine green-based photodynamic therapy for treating melanoma.

The morbidity and mortality of melanoma which accounts for 90% of cutaneous neoplasm-related deaths is growing over the last few decades. Common treatments for melanoma are limited to poor tissue selectivity, high toxicity and drug resistance. Photodynamic therapy (PDT) is an effective adjuvant therapy and could be a promising therapy for melanoma. Multiple mechanisms are involved in PDT2 and programmed cell death (PCD) which comprises of autophagy and apoptosis is likely to be a critical one. Whereas, the molecular mechanism and subsequent effect of PDT-induced autophagy in melanoma are still unclear. In this study, we first analyzed gene expression data in the TCGA3 and GEO4 databases to clarify that PDT-induced-autophagy improved the prognosis of melanoma. The expression of FOS which generally defined as an immediate-early gene (IEG) and related to cell autophagy was found significantly elevated after PDT. To further investigate whether FOS played a key role in PDT-induced-autophagy of melanoma, we first determined the optimum concentration of ICG solution for autophagy observation. Then, relative FOS expression was detected at mRNA and protein level and cell autophagy was observed by western blot and flow cytometry. We found that ICG-PDT treatment could significantly elevate FOS expression in SKCM5 B16 cells, and FOS promoted ICG-PDT-induced cell autophagy. To sum up, our data indicated that FOS was involved in ICG-PDT-induced-autophagy in melanoma and furthermore improved the prognosis of melanoma.

The melanogenic effects and underlying mechanism of paeoniflorin in human melanocytes and vitiligo mice.

Vitiligo is a common depigmentary disease characterized as diagnosis simplicity and cure difficulty in view of the ambiguity of etiology, thus novel and effective treatments are urgently needed. Paeoniflorin, the major active compound extracted from the root of Paeonia lactiflora Pall, a traditional Chinese medicine, has been validated pharmacological properties such as antioxidant stress, a theory participating in the occurrence of vitiligo, but the effect on melanogenesis is still unclear. In this study, melanosythesis effect of paeoniflorin and the potential mechanism were evaluated. We found that treatment with paeoniflorin at the concentration of 10 µg/ml significantly increased melanin content and intracellular tyrosinase activity of human melanocytes, in accordance with the elevation of protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TRP-1). In addition, we also investigated that paeoniflorin promoted phosphorylation of cAMP-response element binding (CREB) and extracellular signal-regulated kinase (ERK) without affecting p38 and c-Jun N-terminal kinase (JNK). These results demonstrated that paeoniflorin had a synergistic effect on normal human melanocytes via ERK/CREB pathway with up-regulation of MITF and TRP-1, enhancing melanin synthesis. Meanwhile, the milder pathological changes in vitiligo mice treat with paeoniflorin also confirmed its potential in treating vitiligo. To sum up, we suggest that paeoniflorin may be a potential medicine of vitiligo treatment in clinical.

Gold-Nanobipyramid-Based Nanotheranostics for Dual-Modality Imaging-Guided Phototherapy.

Multimodality imaging-guided therapy can improve the diagnostics and therapeutics efficiency of cancer. Herein, we developed a light-responsive nanotheranostic agent based on the indocyanine green (ICG) conjugated mesoporous silica coated gold nanobipyramid (GNB@SiO2) (denoted as GNB@SiO2-ICG) for simultaneous fluorescence (FL)/photoacoustic (PA) imaging-guided photothermal therapy (PTT). The GNB@SiO2 with excellent photostability was used for PA imaging as well as PTT. The loaded ICG promised FL imaging and PTT. The feasibility of the cancer theranostic capability of GNB@SiO2-ICG was evaluated from cancer cells to mice. Under the guidance of FL/PA imaging, GNB@SiO2-ICG exhibited remarkably enhanced therapeutic efficacy, which could eliminate the tumor tissues completely without tumor recurrence. This well-defined nanotheranostic nanoplatform that intelligently integrates dual-modality imaging and phototherapy provides an efficient nanoplatform for cancer nanotheranostics.