Quantitative analysis of lesion images to evaluate the efficiency of vascular-targeted photodynamic therapy for port-wine stains: Four case reports.

SIGNIFICANCE: Vascular-targeted photodynamic therapy (V-PDT) is a clinically approved therapeutic approach for treating vascular-related diseases, such as port-wine stains (PWS). For accurate treatment, varying light irradiance is required for different lesions due to the irregularity of vascular size, shape and degree of disease, which commonly alters during different stages of V-PDT. This makes quantitative analysis of the treatment efficiency urgently needed. APPROACH: Lesion images pre- and post- V-PDT treatment of patients with PWS were used to construct a quantitative method to evaluate the differences among lesions. Image analysis techniques were applied to evaluate the V-PDT efficiency for PWS by determining the Euclidean distances and two-dimensional correlation coefficients. RESULTS: According to the image analysis, V-PDT with good treatment efficiency resulted in a larger Euclidean distance and a smaller correlation coefficient compared with the case having lower V-PDT efficiency. CONCLUSIONS: A new method to quantify the Euclidean distances and correlation coefficients has been proposed, which is promising for the quantitative analysis of V-PDT efficiency for PWS.

Simultaneous photoacoustic and ultrasound imaging: A review.

Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that combines the advantages of optical and ultrasound imaging, enabling the generation of images with both optical resolution and acoustic penetration depth. By leveraging similar signal acquisition and processing methods, the integration of photoacoustic and ultrasound imaging has introduced a novel hybrid imaging modality suitable for clinical applications. Photoacoustic-ultrasound imaging allows for non-invasive, high-resolution, and deep-penetrating imaging, providing a wealth of image information. In recent years, with the deepening research and the expanding biomedical application scenarios of photoacoustic-ultrasound bimodal systems, the immense potential of photoacoustic-ultrasound bimodal imaging in basic research and clinical applications has been demonstrated, with some research achievements already commercialized. In this review, we introduce the principles, technical advantages, and biomedical applications of photoacoustic-ultrasound bimodal imaging techniques, specifically focusing on tomographic, microscopic, and endoscopic imaging modalities. Furthermore, we discuss the future directions of photoacoustic-ultrasound bimodal imaging technology.

Photodynamic therapy of vaginal intraepithelial neoplasia-How to do it?

Vaginal intraepithelial neoplasia (VaIN or VAIN), a rare precancerous disease, is difficult to treat. Photodynamic therapy (PDT) is a relatively new modality for the treatment of various precancerous mucosal lesions of the lower genital organs, including VaIN. Due to the special structure and location of the vagina, it is difficult to apply photosensitizer and light irradiation to VaIN lesions. This article provides a tutorial guide on the application of ALA-mediated intravaginal PDT for the treatment of VaIN lesions under different situations.

4D spectral-spatial computational photoacoustic dermoscopy.

Photoacoustic dermoscopy (PAD) is an emerging non-invasive imaging technology aids in the diagnosis of dermatological conditions by obtaining optical absorption information of skin tissues. Despite advances in PAD, it remains unclear how to obtain quantitative accuracy of the reconstructed PAD images according to the optical and acoustic properties of multilayered skin, the wavelength and distribution of excitation light, and the detection performance of ultrasound transducers. In this work, a computing method of four-dimensional (4D) spectral-spatial imaging for PAD is developed to enable quantitative analysis and optimization of structural and functional imaging of skin. This method takes the optical and acoustic properties of heterogeneous skin tissues into account, which can be used to correct the optical field of excitation light, detectable ultrasonic field, and provide accurate single-spectrum analysis or multi-spectral imaging solutions of PAD for multilayered skin tissues. A series of experiments were performed, and simulation datasets obtained from the computational model were used to train neural networks to further improve the imaging quality of the PAD system. All the results demonstrated the method could contribute to the development and optimization of clinical PADs by datasets with multiple variable parameters, and provide clinical predictability of photoacoustic (PA) data for human skin.

Photodynamic Therapy-Induced Anti-Tumor Immunity: Influence Factors and Synergistic Enhancement Strategies.

Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity towards tumor cells by activating photosensitizers (PSs) with light exposure to produce reactive oxygen species (ROS). Compared to traditional treatment strategies such as surgery, chemotherapy, and radiation therapy, PDT not only kills the primary tumors, but also effectively suppresses metastatic tumors by activating the immune response. However, the anti-tumor immune effects induced by PDT are influenced by several factors, including the localization of PSs in cells, PSs concentration, fluence rate of light, oxygen concentration, and the integrity of immune function. In this review, we systematically summarize the influence factors of anti-tumor immune effects mediated by PDT. Furthermore, an update on the combination of PDT and other immunotherapy strategies are provided. Finally, the future directions and challenges of anti-tumor immunity induced by PDT are discussed.

The upregulation of immune checkpoints after photodynamic therapy reducing immune effect for treating breast cancer.

The immune effect induced by photodynamic therapy (PDT) has a limited effect on breast tumor. This study hypothesized that suppressive immune checkpoints on T cells might upregulate after PDT, which may reduce the antitumor effect of PDT for treating breast tumor. This study explored the alteration of immune checkpoint for the first time. A bilateral subcutaneous transplanted breast tumor mice model was established, and right tumors imitated primary tumors, and left tumors imitated distant tumors. Primary tumors were treated with PDT mediated by hematoporphyrin derivatives (HpD-PDT). Costimulatory molecules (ICOS, OX40, and 4-1BB) and immune checkpoints (PD1, LAG-3, CTLA-4, TIM-3, TIGIT) on tumor infiltrating T cells after HpD-PDT were analyzed by flow cytometry. Antitumor and immune effects were also assessed after HpD-PDT combined with anti-PD1 and LAG-3 antibodies. Primary tumors were suppressed, but distant tumors could not be inhibited after HpD-PDT. The number of T cells was increased, but function did not enhance after HpD-PDT. Additionally, costimulatory molecules (ICOS, OX40, and 4-1BB) were not elevated, but the suppressive immune checkpoints on tumor infiltrating T cells were upregulated after HpD-PDT. Notably, PD1+ LAG-3+ CD4+ T and PD1+ LAG-3+ CD8+ T cells were significantly increased. When PD1 and LAG-3 blockade combined with HpD-PDT, both primary and distant tumors were significantly suppressed, and antitumor immune effects were significantly enhanced. HpD-PDT could upregulate the PD1+ LAG-3+ CD4+ T and PD1+ LAG-3+ CD8+ T cells. Dual blockade of PD1 and LAG-3 immune checkpoints can enhance the antitumor effect of HpD-PDT.

In situ detection of human glioma based on tissue optical properties using diffuse reflectance spectroscopy.

Safely maximizing brain cancer removal without injuring adjacent healthy tissue is crucial for optimal treatment outcomes. However, it is challenging to distinguish cancer from noncancer intraoperatively. This study aimed to explore the feasibility of diffuse reflectance spectroscopy (DRS) as a label-free and real-time detection technology for discrimination between brain cancer and noncancer tissues. Fifty-five fresh cancer and noncancer specimens from 19 brain surgeries were measured with DRS, and the results were compared with co-registered clinical standard histopathology. Tissue optical properties were quantitatively obtained from the diffuse reflectance spectra and compared among different types of brain tissues. A machine learning-based classifier was trained to differentiate cancerous versus noncancerous tissues. Our method could achieve a sensitivity of 93% and specificity of 95% for discriminating high-grade glioma from normal white matter. Our results showed that DRS has the potential to be used for label-free, real-time in vivo cancer detection during brain surgery.

Preventing Post-Traumatic Stress Disorder (PTSD) in rats with pulsed 810 nm laser transcranial phototherapy.

Post-traumatic stress disorder (PTSD) is a debilitating condition that occurs following exposure to traumatic events. Current treatments, such as psychological debriefing and pharmacotherapy, often have limited efficacy and may result in unwanted side effects, making early intervention is a more desirable strategy. In this study, we investigated the efficacy of a single dose of pulsed (10 Hz) 810 nm laser-phototherapy (P-PT) as an early intervention for preventing PTSD-like comorbidities in rats induced by single inescapable electric foot shock following the single prolonged stress (SPS&S). As indicated by the results of the open filed test, elevated plus maze test, and contextual fear conditioning test, P-PT prevented the development of anxiety and freezing behaviors in rats exposed to the SPS&S. We also compared the effects of P-PT and continuous wave 810 nm laser-phototherapy (CW-PT) in preventing PTSD-like comorbidities in rats. The results revealed that P-PT was effective in preventing both freezing and anxiety behavior in stressed rats. In contrast, CW-PT only had a preventive effect on freezing behavior but not anxiety. Additionally, P-PT significantly reduced the c-fos expression in cingulate cortex area 1(Cg1) and infralimbic cortex (IL) of stressed rats, while CW-PT had no significant effects on c-fos expression. Taken together, our results demonstrate that P-PT is a highly effective strategy for preventing the occurrence of PTSD-like comorbidities in rats.

Deep-learning visualization enhancement method for optical coherence tomography angiography in dermatology.

Optical coherence tomography angiography (OCTA) in dermatology usually suffers from low image quality due to the highly scattering property of the skin, the complexity of cutaneous vasculature, and limited acquisition time. Deep-learning methods have achieved great success in many applications. However, the deep learning approach to improve dermatological OCTA images has not been investigated due to the requirement of high-performance OCTA systems and difficulty of obtaining high-quality images as ground truth. This study aims to generate proper datasets and develop a robust deep learning method to enhance the skin OCTA images. A swept-source skin OCTA system was employed to create low-quality and high-quality OCTA images with different scanning protocols. We propose a model named vascular visualization enhancement generative adversarial network and adopt an optimized data augmentation strategy and perceptual content loss function to achieve better image enhancement effect with small amount of training data. We demonstrate the superiority of the proposed method in skin OCTA image enhancement by quantitative and qualitative comparisons.

Mapping port wine stain in vivo by optical coherence tomography angiography and multi-metric characterization.

Port wine stain (PWS) is a congenital cutaneous capillary malformation composed of ecstatic vessels, while the microstructure of these vessels remains largely unknown. Optical coherence tomography angiography (OCTA) serves as a non-invasive, label-free and high-resolution tool to visualize the 3D tissue microvasculature. However, even as the 3D vessel images of PWS become readily accessible, quantitative analysis algorithms for their organization have mainly remained limited to analysis of 2D images. Especially, 3D orientations of vasculature in PWS have not yet been resolved at a voxel-wise basis. In this study, we employed the inverse signal-to-noise ratio (iSNR)-decorrelation (D) OCTA (ID-OCTA) to acquire 3D blood vessel images in vivo from PWS patients, and used the mean-subtraction method for de-shadowing to correct the tail artifacts. We developed algorithms which mapped blood vessels in spatial-angular hyperspace in a 3D context, and obtained orientation-derived metrics including directional variance and waviness for the characterization of vessel alignment and crimping level, respectively. Combining with thickness and local density measures, our method served as a multi-parametric analysis platform which covered a variety of morphological and organizational characteristics at a voxel-wise basis. We found that blood vessels were thicker, denser and less aligned in lesion skin in contrast to normal skin (symmetrical parts of skin lesions on the cheek), and complementary insights from these metrics led to a classification accuracy of ∼90% in identifying PWS. An improvement in sensitivity of 3D analysis was validated over 2D analysis. Our imaging and analysis system provides a clear picture of the microstructure of blood vessels within PWS tissues, which leads to a better understanding of this capillary malformation disease and facilitates improvements in diagnosis and treatment of PWS.

Ultrasonic irradiation enhanced the efficacy of antimicrobial photodynamic therapy against methicillin-resistant Staphylococcus aureus biofilm.

Antimicrobial photodynamic therapy (aPDT) is a non-pharmacological antimicrobial regimen based on light, photosensitizer and oxygen. It has become a potential method to inactivate multidrug-resistant bacteria. However, limited by the delivery of photosensitizer (PS) in biofilm, eradicating biofilm-associated infections by aPDT remains challenging. This study aimed to explore the feasibility of combining ultrasonic irradiation with aPDT to enhance the efficacy of aPDT against methicillin-resistant staphylococcus aureus (MRSA) biofilm. A cationic benzylidene cyclopentanone photosensitizer with much higher selectivity to bacterial cells than mammalian cells were applied at the concentration of 10 µM. 532 nm laser (40 mW/cm2, 10 min) and 1 MHz ultrasound (500 mW/cm2, 10 min, simultaneously with aPDT) were employed against MRSA biofilms in vitro. In addition to combined with ultrasonic irradiation and aPDT, MRSA biofilms were treated with laser irradiation only, photosensitizer only, ultrasonic irradiation only, ultrasonic irradiation and photosensitizer, and aPDT respectively. The antibacterial efficacy was determined by XTT assay, and the penetration depth of PS in biofilm was observed using a photoluminescence spectrometer and a confocal laser scanning microscopy (CLSM). In addition, the viability of human dermal fibroblasts (WS-1 cells) after the same treatments mentioned above and the uptake of P3 by WS-1 cells after ultrasonic irradiation were detected by CCK-8 and CLSM in vitro. Results showed that the percent decrease in metabolic activity resulting from the US + aPDT group (75.76%) was higher than the sum of the aPDT group (44.14%) and the US group (9.88%), suggesting synergistic effects. Meanwhile, the diffusion of PS in the biofilm of MRSA was significantly increased by 1 MHz ultrasonic irradiation. Ultrasonic irradiation neither induced the PS uptake by WS-1 cells nor reduced the viability of WS-1 cells. These results suggested that 1 MHz ultrasonic irradiation significantly enhanced the efficacy of aPDT against MRSA biofilm by increasing the penetration depth of PS. In addition, the antibacterial efficacy of aPDT can be enhanced by ultrasonic irradiation, the US + aPDT treatment demonstrated encouraging in vivo antibacterial efficacy (1.73 log10 CFU/mL reduction). In conclusion, the combination of aPDT and 1 MHz ultrasound is a potential and promising strategy to eradicate biofilm-associated infections of MRSA.

M-CSAFN: Multi-Color Space Adaptive Fusion Network for Automated Port-Wine Stains Segmentation.

Automatic segmentation of port-wine stains (PWS) from clinical images is critical for accurate diagnosis and objective assessment of PWS. However, this is a challenging task due to the color heterogeneity, low contrast, and indistinguishable appearance of PWS lesions. To address such challenges, we propose a novel multi-color space adaptive fusion network (M-CSAFN) for PWS segmentation. First, a multi-branch detection model is constructed based on six typical color spaces, which utilizes rich color texture information to highlight the difference between lesions and surrounding tissues. Second, an adaptive fusion strategy is used to fuse complementary predictions, which address the significant differences within the lesions caused by color heterogeneity. Third, a structural similarity loss with color information is proposed to measure the detail error between predicted lesions and truth lesions. Additionally, a PWS clinical dataset consisting of 1413 image pairs was established for the development and evaluation of PWS segmentation algorithms. To verify the effectiveness and superiority of the proposed method, we compared it with other state-of-the-art methods on our collected dataset and four publicly available skin lesion datasets (ISIC 2016, ISIC 2017, ISIC 2018, and PH2). The experimental results show that our method achieves remarkable performance in comparison with other state-of-the-art methods on our collected dataset, achieving 92.29% and 86.14% on Dice and Jaccard metrics, respectively. Comparative experiments on other datasets also confirmed the reliability and potential capability of M-CSAFN in skin lesion segmentation.

Melatonin protects against developmental PBDE-47 neurotoxicity by targeting the AMPK/mitophagy axis.

The neurotoxicity of 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) is closely linked to mitochondrial abnormalities while mitophagy is vital for mitochondrial homeostasis. However, whether PBDE-47 disrupts mitophagy contributing to impaired neurodevelopment remain elusive. Here, this study showed that neonatal PBDE-47 exposure caused learning and memory deficits in adult rats, accompanied with striatal mitochondrial abnormalities, neuronal apoptosis and the resultant neuronal loss. Mechanistically, PBDE-47 suppressed PINK1/Parkin-mediated mitophagy induction and degradation, inducing mitophagosome accumulation and mitochondrial dysfunction in vivo and in vitro. Additionally, stimulation of mitophagy by adenovirus-mediated Parkin or Autophagy-related protein 7 (Atg7) overexpression aggravated PBDE-47-induced mitophagosome accumulation, mitochondrial dysfunction, neuronal apoptosis and death. Conversely, suppression of mitophagy by the siRNA knockdown of Atg7 rescued PBDE-47-induced detrimental consequences. Importantly, melatonin, a hormone secreted rhythmically by the pineal, improved PBDE-47-caused neurotoxicity via preventing neuronal apoptosis and loss by restoring mitophagic activity and mitochondrial function. These neuroprotective effects of melatonin depended on activation of the AMP-activated protein kinase (AMPK)/Unc-51-like kinase 1 (ULK1) signaling. Collectively, these data indicate that PBDE-47 impairs mitophagy to perturb mitochondrial homeostasis, thus triggering apoptosis, leading to neuronal loss and consequent neurobehavioral deficits. Manipulation of the AMPK-mitophagy axis via melatonin could be a novel therapeutic strategy against developmental PBDE-47 neurotoxicity.

A water-dependent reversible photoacidity strategy for cancer treatment.

In the reported mechanisms of reversible photoacidity, protons were dissociated from compounds which contained hydroxyl, indazole or formed hydroxyl via intramolecular hydrogen abstraction under irradiation. Herein, a water-dependent reversible photoacidity (W-RPA) mechanism mediated by a thiadiazoloquinoxaline compound (TQs-Th-PEG5) has been found, in which the proton is not dissociated from TQs-Th-PEG5 itself but from a water locked by TQs-Th-PEG5 under the irradiation of a 660 nm laser. After turning off the laser, the produced acid will disappear quickly. This process is repeatable with no consumption of TQs-Th-PEG5. More importantly, water is indispensable. Furthermore, it is confirmed that there is no other element involved in the process except TQs-Th-PEG5, light and water. Excitingly, W-RPA therapy mediated by TQs-Th-PEG5 nanoparticle exhibits remarkable antitumor effect both in vitro and in vivo, especially in hypoxic tumors with diameter larger than 10 mm owing to its oxygen-independent feature. This study not only discovers a W-RPA mechanism but also provides a novel phototherapy strategy for cancer treatment.

A Novel Pyroptotic and Inflammatory Gene Signature Predicts the Prognosis of Cutaneous Melanoma and the Effect of Anticancer Therapies.

Purpose: The purpose of this study was to construct a gene signature comprising genes related to both inflammation and pyroptosis (GRIPs) to predict the prognosis of patients with cutaneous melanoma patients and the efficacy of immunotherapy, chemotherapy, and targeted therapy in these patients. Methods: Gene expression profiles were collected from The Cancer Genome Atlas. Weighted gene co-expression network analysis was performed to identify GRIPs. Univariable Cox regression and Lasso regression further selected key prognostic genes. Multivariable Cox regression was used to construct a risk score, which stratified patients into high- and low-risk groups. Areas under the ROC curves (AUCs) were calculated, and Kaplan-Meier analyses were performed for the two groups, following validation in an external cohort from Gene Expression Omnibus (GEO). A nomogram including the GRIP signature and clinicopathological characteristics was developed for clinical use. Gene set enrichment analysis illustrated differentially enriched pathways. Differences in the tumor microenvironment (TME) between the two groups were assessed. The efficacies of immune checkpoint inhibitors (ICIs), chemotherapeutic agents, and targeted agents were predicted for both groups. Immunohistochemical analyses of the GRIPs between the normal and CM tissues were performed using the Human Protein Atlas data. The qRT-PCR experiments validated the expression of genes in CM cell lines, Hacat, and PIG1 cell lines. Results: A total of 185 GRIPs were identified. A novel gene signature comprising eight GRIPs (TLR1, CCL8, EMP3, IFNGR2, CCL25, IL15, RTP4, and NLRP6) was constructed. The signature had AUCs of 0.714 and 0.659 for predicting 3-year overall survival (OS) in the TCGA entire and GEO validation cohorts, respectively. Kaplan-Meier analyses revealed that the high-risk group had a poorer prognosis. Multivariable Cox regression showed that the GRIP signature was an independent predictor of OS with higher accuracy than traditional clinicopathological features. The nomogram showed good accuracy and reliability in predicting 3-year OS (AUC = 0.810). GSEA and TME analyses showed that the high-risk group had lower levels of pyroptosis, inflammation, and immune response, such as lower levels of CD8+ T-cell infiltration, CD4+ memory-activated T-cell infiltration, and ICI. In addition, low-risk patients whose disease expressed PD-1 or CTLA-4 were likely to respond better to ICIs, and several chemotherapeutic and targeted agents. Immunohistochemical analysis confirmed the distinct expression of five out of the eight GRIPs between normal and CM tissues. Conclusion: Our novel 8-GRIP signature can accurately predict the prognosis of patients with CM and the efficacies of multiple anticancer therapies. These GRIPs might be potential prognostic biomarkers and therapeutic targets for CM.

Multiscale confocal photoacoustic dermoscopy to evaluate skin health.

Background: Photoacoustic dermoscopy (PAD) is a promising branch of photoacoustic microscopy (PAM) that can provide a range of functional and morphologic information for clinical assessment and diagnosis of dermatological conditions. However, most PAM setups are unsuitable for clinical dermatology because their single-scale mode and narrow frequency band result in insufficient imaging depth or poor spatiotemporal resolution when visualizing the internal texture of the skin. Methods: We developed a multiscale confocal photoacoustic dermoscopy (MC-PAD) with a multifunction opto-sono objective that could achieve high quality dermatological imaging. Using the objective to coordinate the spatial resolution and penetration depth, the MC-PAD was used to visualize pathophysiological biomarkers and vascular morphology from the epidermis (EP) to the dermis, which enabled us to quantify skin abnormalities without using exogenous contrast agents for human skin. Results: The MC-PAD was shown to have the ability to differentiate between different types of cells (such as red blood cells and melanoma cells), image and quantify pigment of the skin, and visualize skin morphology and blood capillary landmarks. The MC-PAD detected a significant difference in the structures of some pigmented and vascular lesions of skin diseases compared with that of healthy skin (P<0.01). The café au lait macule (CALM) skin type was found to have a relatively higher melanin concentration and thicker stratum basale (SB) in the EP than healthy skin. The dermal vascular network of skin that had a port wine stain (PWS) had greater diameters and a denser distribution than healthy skin, as reported in clinical trials. Conclusions: The MC-PAD has a broad range of applications for the diagnosis of human skin diseases and evaluation of the curative effect of treatments, and it can offer new perspectives in biomedical sciences.

Optimization of photo-biomodulation therapy for wound healing of diabetic foot ulcers in vitro and in vivo.

Unclear optical parameters make photo-biomodulation (PBM) difficult to implement in diabetic foot ulcer (DFU) clinically. Here, 12 wavelengths (400-900 nm) were used to conduct PBM to heal DFU wounds in vitro and in vivo. PBM at 10 mW/cm2 and 0.5-4 J/cm2 with all 12 wavelengths promoted proliferation of diabetic wound cells. In a mimic DFU (mDFU) rat model, PBM (425, 630, 730, and 850 nm, and a combination light strategy) promoted mDFU healing. The positive cell proliferation, re-epithelialization, angiogenesis, collagen synthesis, and inflammation were possible mechanisms. The combination strategy had the best effect, which can be applied clinically.

Enhanced antimicrobial activity through the combination of antimicrobial photodynamic therapy and low-frequency ultrasonic irradiation.

The rapid increase of antibiotic resistance in pathogenic microorganisms has become one of the most severe threats to human health. Antimicrobial photodynamic therapy (aPDT), a light-based regimen, has offered a compelling nonpharmacological alternative to conventional antibiotics. The activity of aPDT is based on cytotoxic effect of reactive oxygen species (ROS), which are generated through the photosensitized reaction between photon, oxygen and photosensitizer. However, limited by the penetration of light and photosensitizers in human tissues and/or the infiltration of oxygen and photosensitizers in biofilms, the eradication of deeply located or biofilm-associated infections by aPDT remains challenging. Ultrasound irradiation bears a deeper penetration in human tissues than light and, sequentially, can promote drug delivery through cavitation effect. As such, the combination of ultrasound and aPDT represents a potent antimicrobial strategy. In this review, we summarized the recent progresses in the area of the combination therapy using ultrasound and aPDT, and discussed the potential mechanisms underlying enhanced antimicrobial effect by this combination therapy. The future research directions are also highlighted.

Optothermophoretic flipping method for biomolecule interaction enhancement.

The widely used surface-based biomolecule sensing scheme has greatly facilitated the investigation of protein-protein interactions in lab-on-a-chip microfluidic systems. However, in most biosensing schemes, the interactions are driven in a passive way: The overall sensing time and sensitivity are totally dependent on the Brownian diffusion process, which has greatly hindered their efficiency, especially at low concentration levels or single-molecule analysis. To break this limitation, we developed an all-optical active method termed optothermophoretic flipping (OTF). It is the first temporal modulated method that biomolecules were enriched and pushed to their counterparts for effective contact via a flipped thermophoresis. As a proof-of-concept experiment, we tested its performance via antibody-antigen binding on a surface plasmon resonance imaging (SPRi) platform. Compared with the interaction solely based on Brownian diffusion, we achieved a 23.6-fold sensitivity increment in biomolecule interactions sensing. This method has opened new opportunities for various biosensing platforms that require high-sensitivity in colloidal sciences and biochemical studies.

In vitro and in vivo evaluation of a chlorin-based photosensitizer KAE® for cancer treatment.

BACKGROUND: Photodynamic therapy (PDT) has been approved for the clinical treatment of cancers. Photosensitizer (PS) is a crucial element of PDT. In the current study, in vitro and in vivo evaluation of a chlorin-based photosensitizer KAE® was performed. METHODS: The physicochemical characteristics of KAE® were compared with chlorin e6. The intracellular distribution of KAE® in HeLa cells was observed by laser scanning confocal microscopy. Reactive oxygen species (ROS) generation was detected through a 2', 7-dichlorodihydrofluorescein diacetate probe. The pharmacokinetics of KAE® was studied in mice. The photodynamic activities of KAE® and porphyrin based PSs were compared both in vitro and in vivo. The biosafety of KAE® in mice was evaluated by pathological section observation, blood routine examination and biochemistry assays. RESULTS: KAE® was readily dissolved in an aqueous solvent in a clinically acceptable concentration and showed a strong absorption at around 660 nm. Most of KAE® was located in the mitochondria of the tumor cells. Compared with hematoporphyrin derivative and 5-aminolevulinic acid, KAE® displayed a higher efficiency in cell killing. Furthermore, it could be completely eliminated from mouse body in 2 days. KAE® had no toxicity to mice under the tested dosage. CONCLUSIONS: Our results suggested that KAE® is an effective and safe PS for PDT in cancer therapy and has a promising prospect for clinical application.