This PDF file contains the front matter associated with SPIE Proceedings Volume 10879, including the Title Page, Copyright information, Table of Contents, Author and Conference Committee lists.

In addition to direct killing of tumor cells, PDT can enhance anti-tumor immune responses in the host. It is well known that PDT-induced acute inflammation facilitates PDT-enhanced anti-tumor immunity. Our studies in murine colon carcinoma model demonstrates that PDT induces a short-lived burst of PGE2 in tumor draining lymph node which is critical for ability of PDT to induce acute inflammation. Using a selective COX2 inhibitor NS398, we demonstrate that this short-lived PGE2 burst regulates PDT-enhanced anti-tumor immunity and overall PDT efficacy. These results bring to light a beneficial role of PDT-induced acute expression of PGE2 on PDT-enhanced anti-tumor immunity. Although long term administration of NSAIDS is the current clinical practice for PDT, our research emphasizes on delaying the timing of NSAID administration to after acute inflammation is resolved for optimal response.

Human squamous cell carcinoma is the major type of oral cancer. Traditional methods for human oral cancers treatments are surgery, chemotherapy and radiotherapy. Because photodynamic therapy is a noninvasive alternative for oral cancer therapy. A novel photosensitizer was first constructed in nanoparticles, for photodynamic therapy. Oncogene silencing RNA was encapsulated into nanoparticles to silence oncogene expression. Two treatments were combined for cancer treatment.Results suggest that the combination therapy could be a potential treatment to develop for human oral cancer in the future.

NIR-triggered photodynamic therapy via antigen-capturing upconversion nanoparticle enhances cancer immunotherapy Meng Wang,a,b Lu Wang,a Benqing, Zhou,a,b Feifan Zhou,b Wei R. Chen*a a Biophotonics Research Laboratory, Center of Interdisciplinary Biomedical Education and Research, College of Mathematics and Science, University of Central Oklahoma, Oklahoma, 73034, USA b Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, P. R. China Abstract Photodynamic therapy (PDT) as a promising cancer treatment strategy has the ability to induce antitumor immune responses. However, conventional PDT using photosensitizers activated by visible light has limited penetration depth, which attenuates severely the effectiveness of induced immune responses. We developed an NIR-triggered antigen-capturing nano-photosensitizer, using upconversion nanoparticles (NPs), indocyanine green (ICG), Rose Bangel (RB), a photosensitizer, and maleimides (mal) for cancer treatment. NP/ICG/RB-mal can be used not only for photodynamic therapy, but also for cancer immunotherapy though in situ tumor-associated antigens capturing. With ICG, NP/ICG/RB-mal increases the UCNP emission intensity to achieve higher PDT efficiency and, at the same time, enhances photothermal therapy (PTT). Tumor-associated antigens arising from the PDT/PTT can further be captured by NP/ICG/RB-mal in situ, and delivered to antigen-presenting cells (APCs) to induce a tumor-specific immune response. As a result, a remarkable in vivo synergistic therapeutic effect is achieved using NP/ICG/RB-mal under laser irradiation in treating metastatic tumors.

Vascular targeted photodynamic therapy (V-PDT) has shown satisfied efficiency in treating vascular-related diseases including age-related macular degeneration, port-wine stains (PWS), and prostate cancer. Its efficacy is a complex function of photosensitizer (PS) uptake, oxygen concentration, PS-activating light dose and tissue optical properties. In order to non -invasively monitor PS distribution and photobleaching, blood vessel contraction and blood flow velocity for V-PDT response, a multimode optical imaging (MOI) system was developed to capture PS fluorescence image, narrow band image and laser speckle image, respectively. V-PDT in vivo studies were performed, which suggests that our MOI system is capable of monitoring dynamic response during V-PDT treatment.

Pancreatic cancer is one of the most challenging diseases. Patients with metastatic pancreatic cancer has a poor prognosis with a 3% five-year survival rate. The high mortality rate is largely due to two major factors: the severely limited resectability and extremely high rate of metastasis. We applied laser immunotherapy (LIT) to treat a highly metastatic, poorly immunogenic pancreatic tumor model (Panc02-H7) in mice. Subcutaneous tumors were irradiated by a near-infrared laser non-invasively and orthotopic tumors were irradiated by the laser interstitially, followed by intratumoral injection of glycated chitosan, an immunoadjuvant. Long-term survival and tumor-specific immunity were observed after LIT treatment. The effectiveness of LIT in treating pancreatic tumors demonstrated in this study could lead to a feasible modality for this deadly disease.

Current treatment of advanced (stage III, IV) melanoma utilizes immunotherapy (for BRAF mutation negative tumors), and immunotherapy and/or targeted therapy for BRAF mutation positive tumors. This has significantly improved prognosis in advanced melanoma. However, the technology is far from ideal. Significant cost and morbidity from immunotherapy are problems as it is currently constituted (blind use of high-dose T-cell stimulating drugs such as ipilimumab, pembrolizumab and nivolumab for prolonged periods of administration). A typical course of these drugs for one individual may exceed a half a million dollars over a two-year period; cost alone may limit further deployment of this technology to other tumor types. Another serious limitation of this excessive use of T-cell stimulation drugs are autoimmune side effects, which are increased by higher dosages and prolonged periods of administration. Pretreatment with adjuvant immunotherapy techniques such as laser immunotherapy (LIT), which combines laser irradiation and topical application of imiquimod, an immunoadjuvant, may provide a solution. LIT could potentiate the effectiveness of checkpoint inhibitors, thus significantly lowering the dose required and shortening the necessary period of administration. This, in turn, leads to a significant cost savings as well as dramatic reductions in morbidity from side effects, while simultaneously enhancing the effectiveness of treatment. Anecdotal evidence of these effects will be introduced and the further development of laser immunotherapy plus checkpoint inhibitors in the near future will be discussed.

Nasopharyngeal carcinoma (NPC) is a high incidence cancer in southern China and southeast Asia. For the growth and recurrence are in the concealed pharynx and larynx, NPC is difficult to be early diagnosed and effectively treated. Therefore, it is an ideal way to develop strategy for early targeted diagnosis and treatment. R4FLTV, a peptide which can specifically target human nasopharyngeal carcinoma tumor 5-8F, combined with nanoparticle could realize combination of diagnosis and treatment for subcutaneous 5-8F tumor model and lung metastasis in nude mice. By using pull down technology and protein spectrum analysis technique, we found that the ALDH3A2 could be a receptor and molecular marker in the 5-8F cells which targeted by R4FLTV peptide.

Stroke and traumatic brain injury are often associated with formation of brain edema, which is a potentially fatal pathological state provoking extensive accumulation of fluid in the brain tissues resulting in elevation of intracranial pressure and leading to impaired nerve function. There is only symptomatic anti-edema therapy is currently available. Therefore, the development of novel strategies to remove edema fluid is required. The brain edema is classified as vasogenic or cytotoxic edema, which associated with excess accumulation of fluid (edema) around capillaries resulting from disruption of the blood-brain barrier (BBB) or intracellular spaces (cell swelling) of the brain, respectively. In this brief review, we discuss possible mechanisms underlying brain edema formation and new strategies in development of novel of anti-edema drugs.

By adopting a lipoprotein-mimicking peptide self-assembly principle, we created the high density lipoprotein (HDL)-liked peptide-phospholipid scaffold (HPPS), a sub-30 nm core-shell lipid nanoparticle stabilized by apoA-1 mimetic peptides. The HPPS nanocarrier adds a new dimension to the core-shell nanoparticle families particularly valuable for the intracellular delivery of imaging agents, therapeutic peptides or immunomodulators to tumor cells (e.g., melanoma) and immune cells (e.g., dendritic cell and tumor-associated macrophage) in vivo. Recently, we developed HPPS as a carrier to deliver antigen peptides (Aps) to mature dendritic cells (mDCs) in lymph node, which successful elicited desiring anti-tumor immune response. The injection of Ap-HPPS allowed long-term tracking of its flow into lymph nodes using NIR imaging. More importantly, Ap-HPPS exhibited the ability to activate immature DCs and could be directly used as an effective targeting vaccine for in vivo cancer prevention without the need of immunologic adjuvants. We also developed a dual-targeting nanoparticles (M2NPs) for melanoma immunotherapy via delivering small interfering RNA to M2-like tumor-associated macrophages (TAMs). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, it specifically blocked the survival signal of M2-like TAMs and deplete them from tumors. Meanwhile, it also inhibited immunosuppressive IL-10 and TGF-β production, and increased immuno-stimulatory cytokinesexpression and CD8+ T cell infiltration in tumor microenvironment. Thus, the dual-targeting property of M2NPs combined with RNA interference provide a potential strategy of molecular-targeted cancer immunotherapy for clinical application.

Malignant melanoma, developing from melanocytes, is a kind of high metastatic tumor. Circulating melanoma cells, as a marker for metastasis development, are found in blood or lymphatic system at the early stage. Thus, quantitative detection of circulating melanoma cells has great significance to diagnose carcinoma and monitor tumor metastasis. In contrast to in vitro detection methods and in vivo fluorescence-based flow cytometry (IVFC), the in vivo photoacoustic flow cytometry (PAFC) utilizes melanoma cells’ predominant optical absorption in the near-infrared range over other absorbers to receive the photoacoustic (PA) signals without fluorescent dye labeling in a non-invasive way. The sensitivity of the PAFC system was verified by in vitro and in vivo experiments. Besides, we solves the technical problem that blood vessels cannot be positioned in the process of in vivo detection by designing the laser signal positioning navigation system using frequency doubling technique. PAFC provides a new tool for in vivo, label-free, and noninvasive detection of circulating tumor cells (CTCs) and has strong practicality and favorable clinical prospects.

At the present time a new direction of theranostics associated with using of nanostructured multifunctional carriers is developed rapidly. Appreciative examples of such carriers are core-shell nanoparticles, liposomes, polymer micelles, capsules produced by Layer by Layer assembly (LbL) method. Every type of nanostructured carriers has its own advantages and disadvantages. Undoubted advantages of LbL capsules are high loading capacity, wide range of possible internal payloads and wide possibilities of controlling physical and chemical properties of nanostructured carriers by variation of shell structure, thickness and its chemical composition [М.Delcea, et al, Adv. drug delivery reviews, 2011, 63(9), 730, A.S.Timin, et al, Adv. Mater. Interfaces,2016, 4, 1600338]. Application of nanostructured carriers is limited by absence of methods for its in vivo visualization with sufficient spatial resolution and significant tissue penetration depth [A.S.Timin, et al, Adv. Mater. Interfaces, 2016, 4,1600338]. One of the method that allows to visualize and to detect the nanostructured carriers efficiently is a photoacoustic (PA) method. PA approach allows to use the photoacoustic cytometry in vivo [E.I. Galanzha et al, Cancer Res. 2009, 69, 7926]. It is also very important for detection and killing of free circulating cancer cells required for early cancer diagnostics and decreasing the metastases probability [E.I. Galanzha, et al, J. Biophotonics, 2009, 2, 725]. Unique combination of photoacoustic cytometry and nanostructured carriers prepared by LbL assembly approach gives clinicians and researchers significant advantages in the developing of new therapy method based on delivery of nanostructured carriers loaded by bioactive substances into lesion focus and also their visualization and remote controlled release of encapsulated bioactive substances using PA approach. Visualization of two types of nanostructured carriers produced by LbL assembly method was demonstrated recently in diluted and undiluted blood [E.I. Galanzha, et al, J. Biophotonics, 2009, 2, 725]. It was established that hollow microcapsules exhibited greater photoacoustic signal comparing to core-shell type of microparticles with the same composition of polymeric shell [E.I. Galanzha, et al, J. Biophotonics, 2009, 2, 725]. Nevertheless, there are no known examples of in vivo photoacoustic detection of LbL nanostructured carriers, therefore the main goal of present study is formation of biocompatible nanostructured carriers (BNCs) that will exhibit giant photoacoustic signal allowing in vivo detection of such structures. It was demonstrated for the first time, the super (giant) PA contrast of BNCs both in vitro and in vivo. It was verified the unique PA characteristics of these advanced contrast agents using PA flow cytometry diagnostic platform. The obtained data suggest the high PA contrast of BNCs that can be associated with synergistic plasmonic, thermal and acoustic effects, especially in nonlinear mode with nanobubble formation in overheated absorbing layers, in particular gold nanoclusters between two light transparent shells. This work was partly supported by RFBR (project №18-29-08046), the Government of the Russian Federation (grant no. 14.Z50.31.0044 to support scientific research projects implemented under the supervision of leading scientists at Russian institutions and Russian institutions of higher education) and Saratov State University.

The purpose of this investigation is to verify the feasibility of using deep learning technology to generate an image marker for accurate stratification of cervical cancer patients. For this purpose, a pre-trained deep residual neural network (i.e. ResNet-50) is used as a fixed feature extractor, which is applied to the previously identified cervical tumors depicted on CT images. The features at average pooling layer of the ResNet-50 are collected as initial feature pool. Then discriminant neighborhood embedding (DNE) algorithm is employed to reduce the feature dimension and create an optimal feature cluster. Next, a k-nearest neighbors (k-NN) regression model uses this cluster as input to generate an evaluation score for predicting patient’s response to the planned treatment. In order to assess this new model, we retrospectively assembled the pre-treatment CT images from a number of 97 locally advanced cervical cancer (LACC) patients. The leave one out cross validation (LOOCV) strategy is adopted to train and optimize this new scheme and the receiver operator characteristic curve (ROC) is applied for performance evaluation. The result shows that this new model achieves an area under the ROC curve (AUC) of 0.749 ± 0.064, indicating that the deep neural networks enables to identify the most effective tumor characteristics for therapy response prediction. This investigation initially demonstrates the potential of developing a deep learning based image marker to assist oncologists on categorizing cervical cancer patients for precision treatment.

Flow cytometry is an important technique in biomedical discovery for cell counting, cell sorting and biomarker detection. In vivo flow cytometers based on one-photon or two-photon excited fluorescence have been developed for more than a decade. One drawback of laser beam scanning two-photon flow cytometer is that two-photon excitation volume is very small due to short Rayleigh range of focused Gaussian beam. Hence, the sampling volume is much smaller than one-photon flow cytometer, which makes it challenging to count or detect rare circulating cells in vivo. Non-diffracting beam like Bessel beams and Airy beams have narrow intensity profiles with an effective spot size (FWHM) as small as several wavelengths, making them comparable to Gaussian beams. More significantly, the theoretical depth of field (propagation distance without diffraction) can be infinite, making them an ideal solution as a light source for scanning beam flow cytometry. The trade-off of using Airy beams rather than Gaussian beam is the fact that Airy beams have side lobes that contribute to background noise. Two-photon excitation can reduce this noise as the excitation efficiency is proportional to intensity squared. Therefore, we developed a two-photon flow cytometer using 2D Airy beams to form a light sheet that intersects the blood vessel. The set up can successfully detect and count flowing tumor cells in micro channel.

An essential goal of x-ray phase-sensitive imaging is to provide quantitative information such as tissue’s phase maps and electron densities. Various phase retrieval methods have been developed for this task. One such retrieval method-based phase-attenuation duality (PAD) principle and requires only a single exposure for the phase retrieval. We have developed a multi-material loaded soft tissue phantom that can be used for the investigate the accuracy of the PAD-based method in retrieving the phase maps and electron tissue densities. The phantom consists of five inserts; muscle, lung, breast, adipose and Polymethyl methacrylate (PMMA). Each insert had a diameter of 5 mm and a length of 8.2 mm, respectively. The inserts were fitted in a 3D printed circular disk. An x-ray phase sensitive prototype was used to image a PMMA slab for testing to compare the accuracy of the retrieved phase maps with the theoretically estimated values. With the PAD-based method, the average phase value was about -200 radians while the theoretical estimate was -185 radians. A comprehensive future study will be conducted with the newly design phantom to demonstrate further the potential benefits of using x-ray phase-sensitive imaging for the quantification and identification of tissues.

Nanoparticle-based combination therapy may provide an effective therapeutic strategy. Herein, we show that bovine serum albumin (BSA)-bioinspired gold nanorods (GNRs) loaded with immunoadjuvant for combined photothermal therapy (PTT) and immunotherapy for treatment of melanoma. In this work, cetyltrimethylammonium bromide (CTAB) coated GNRs were successively decorated with polyethylene glycol (PEG) and BSA, and loaded with an immunoadjuvant imiquimod (R837). The synthesized mPEGGNRs@ BSA/R837 nanocomplexes could significantly induce immune response in vitro. Furthermore, under near-infrared (NIR) irradiation could effectively kill tumor cells. The nanocomplex-based PTT in combination with immunotherapy may be potentially employed as an effective strategy for the treatment of melanoma and other metastatic cancers.

We here report on the synthesis and characterization of two nanoparticles focused on cancer treatment via laser immunotherapy (LIT), which is a novel cancer treatment modality with the ability to eradicate primary tumors directly and induce an immune response to destroy distant metastases. This method makes use of a photosensitizing agent and an immunoadjuvant to aide in the efficacy and targeting of a laser treatment. In consideration of ways to bring those materials to the tumor site, we investigated the use of various nanoparticles as targeted delivery agents. Due to the tendency of cancerous cells to overexpress low-density lipoprotein receptors (LDLR) to fulfill their heightened need for cholesterol, as well as due to the previously documented ability of low-density lipoproteins (LDL) to be reconstituted with other materials, these naturally occurring nanoparticles served as the base to be combined with reduced graphene oxide (rGO) and form a therapeutic nanocompound dubbed rGO-LDL. (R)-9bMS, a small molecule inhibitor, is known to significantly hinder the proliferation of triple-negative breast cancer cells—a tumor model particularly resistant to treatment. For this reason, (R)-9bMS was selected, and the photosensitizing agent, indocyanine green (ICG) was combined with it into a nanoparticle geared towards use in LIT.

Photothermal therapy is a tumor target therapy, which can induce temperature increase by laser in tumor tissue to eliminate cancer cells, without affecting surrounding healthy tissue. The temperature distribution in the tumor tissue directly determine the therapeutic efficacy. Therefore, real-time temperature monitoring is particularly important during photothermal therapy. However, accurate real-time temperature measurements in deep tissue still face many obstacles. This paper shows the feasibility of photoacoustic technology for real-time temperature monitoring with or without nanomaterials as photoacoustic contrast agents.

To minimize thermal injury, the temperature monitoring with a proportional-integrative-derivative (PID) controller was applied for photothermal treatment of tumors. The thermocouple was used to estimate the temperature. However, it is impossible for thermocouple to measure the spatio-temporal developments of the temperature in tissue. In this work, we present temperature feedback-controlled photothermal treatment based on thermal infrared imager. Experiments demonstrated comparable thermal behaviors in temperature distribution and the degree of irreversible tissue denaturation for the different PID-controlled applications. Integration of temperature feedback with thermal infrared imager-assisted photothermal treatments can provide a feasible therapeutic modality to treat tumors in an effective manner.

Mulberry, as medicinal and edible traditional Chinese herb， has many physiological functions. The present study aims to evaluating the antioxidant activity in vitro and immune modulation of mulberry extracts (ME). The antioxidant ability of ME was comprehensively evaluated by different systems, including the scavenging rates of DPPH and ABTS radical. The mice spleen lymphocyte transformation experiment and the mice peritoneal macrophage phagocytosis chicken red blood cells test were used to observe the effects of ME on specific cellular immunity and nonspecific immunity. The results showed that the IC₅₀ of ME on DPPH and ABTS radical were 521.10 and 1049.44 μg/mL, respectively. In addition, ME can promote the proliferation of spleen lymphocytes and strengthen the phagocytic function of monocyte macrophages. Mulberry has antioxidant benefit and immune boosting effect, which provide a reference for more adequate development and utilization of mulberry resources.

Ulcerative colitis (UC) is a chronic and refractory inflammatory disorder of the colon and rectum with increasing morbidity in recent years. Lian-ai jian (LAJ), a Chinese medicinal herb decoction, including two herbs: Coptidis Rhizoma and Artemisiae Argyi Folium. We group them according to the ancient Chinese medical books "Songfengshuoyi", and investigate the anti-inflammatory, antioxidant activity and protective effect on UC of this compound. Dextran sulfate sodium salt (DSS)-induced colitis mice were used to assess its protective effect on UC. We also determined the anti-inflammatory ability of LAJ by measuring the inhibition of IL-1β, IL-6 and TNF-α expression in LPS stimulated RAW 264.7 macrophages. The inhibition of Nitric oxide (NO) production, iNOS expression in RAW 264.7 macrophages and extracellular NO scavenging ability were used as indicators to evaluate the antioxidant activity of LAJ. The results showed that LAJ had strong anti-inflammatory, antioxidant activity and reduced the disease activity index and colon shortening of mice.

Huzhentongfeng (HZTF) is a compound extract developed by Guangzhou (Jinan) Biomedical Research and Development Center for treating gout. To investigate the antioxidative activity and anti-inflammatory activity of HZTF, the scavenging activity of hydroxyl radical, ferrous ions chelating ability and ferric reducing antioxidant power (FRAP) were used as indicators to evaluate the antioxidant activity and the lipopolysaccharide(LPS)-induced RAW264.7 macrophages were used to assess its anti-inflammatory activity. The results showed that HZTF had certain antioxidant activity, the IC50 values of HZTF in hydroxyl radical scavenging activity and ferrous ions chelating ability are 163.83 ± 10.49 and 899.72 ± 20.98 μg/mL, respectively and the FRAP value of HZTF are 8.97 ± 0.63 mol FeSO4/g. Moreover, HZTF significantly reduced IL-1β, IL-6, TNF-α, iNOS expression and NO production in LPS-induced RAW264.7 macrophages (P < 0.05), which demonstrate that HZTF have good potential to be developed as antioxidant or anti-inflammatory medicines.

As the traditional Chinese medicine, artemisiae argyi folium has various functions such as analgesia, antitumor, and anti-hypertension. To study antioxidant activity of artemisiae argyi folium (AAF) in vitro. The antioxidant activity of AAF was evaluated by ABTS assay, DPPH experiment, OH test and lipid peroxidation. The hydrogen peroxide-induced RAW264.7 cell oxidative damage model was established to assess its antioxidant activity. The results showed that the AAF had strong antioxidant activity and the IC50 on ABTS radicals, DPPH radicals and hydroxyl radicals were 80.88, 813.63, 2458.67 and 94.86μg/ml. MTT experiments showed that AAF was not cytotoxic. The quantitative polymerase chain reaction demonstrate the antioxidant activity of AAF. AAF has great potential for development.

Laser Immunotherapy is a recently-developed treatment for metastatic cancers that synergistically applies photothermal laser irradiation in conjunction with a local immunoadjuvant to induce a host anti-cancer immune response. We have used laser immunotherapy to treat orthotopic pancreatic tumors in mice. In this study, we used magnetic resonance imaging to guide laser immunotherapy for interstitial treatment of metastatic pancreatic tumors in mice. Furthermore, we used MRI to investigate tumor location, guide laser treatment, and monitor the photothermal effects using proton resonance frequency shift thermometry. Our results indicate that laser immunotherapy could be an effective modality for late-stage pancreatic cancer patients, and that MRI thermometry can effectively monitor treatment for guidance.

Gold nanorods (GNRs) have the potential for cancer treatment as tumor-targeting photosensitizers due to their strong absorption of near-infrared light. The purpose of this project was to study the subcellular localization of GNRs in cancerous to optimize cancer treatment using irradiation at appropriate wavelength. Subcellular localization of gold nanorods has been shown to have a significant impact on the retention or exclusion of GNRs within the cells as well as cell viability and morphology. GNRs were functionalized with a fluorescent dye, incubated with cells, and then imaged using a fluorescent microscope. Our results demonstrated the localization of GNRs in cancer cell mitochondria and lysosomes, which corroborates the findings of other studies. Further studies will determine the functions of the subcellular GNRs under irradiation of laser of appropriate wavelengths. Our research could lead to a targeted, effective nanotechnology based laser immunotherapy.

Alzheimer's disease (AD) is a chronic neurodegenerative disease. It is generally believed that there are some connections between AD and amyloid protein plaques in the brain. The typical symptoms of AD are memory and spatial learning difficulties, language disorders, loss of motivation and behavioral issues. Currently, the main therapeutic method is pharmacotherapy, which temporarily relieves symptoms, and yet brings with some side effects. Near infrared (NIR) light therapy has been studied in a range of single and multiple irradiation protocols in previous studies and was found beneficial for neuropathology. In our research, we demonstrated the effect of NIR light on AD through transgenic mouse model. We designed an experimental apparatus consisted of a box with a LED array emitting NIR light inside. After the treatment, we assessed the effects of infrared light by testing cognitive performance of mice in Morris water maze, and detecting plaque load by immunofluorescence analysis. Our results show that NIR therapy is able to attenuate the Aβ burden and cognitive deficits in the mouse model. It might provide a novel and safe way to treat AD.