Photobiomodulation (PBM), utilizing the low power light in visible or near-infrared (NIR) spectrum to trigger biological responses in the cells and tissues, has been considered as a possible therapeutic strategy for Alzheimer’s disease (AD), while its specific mechanism has remained elusive. Here, we provide evidences that the cognition and memory impairment of AD mouse model can be ameliorated by 1070-nm light via reducing cerebral Aβ burden, the hallmark of AD. Our study suggests the important roles of microglia and cerebral vessels in the treatment of 1070-nm light to AD mice, and provide a framework for developing novel therapeutic approach for AD.

Photobiomodulation (PBM) using near-infrared (NIR)-II light has been shown to enhance anti-cancer immunity by reducing oxidative stress, promoting proliferation, and reducing PD-1 expression in tumor-infiltrating CD8+ T cells, ultimately suppressing tumor progression. Meanwhile, photoimmunotherapy (PIT) using NIR light has also shown promise in cancer treatment, inducing a strong anti-cancer immune response. Combining PBM with laser-based phototherapy, including PIT, could have the potential to amplify their therapeutic effects maximally, offering a promising avenue for developing safe and effective cancer therapies.

We investigated the “laser adjuvant” that improved vaccine efficacy, via combining non-invasive near-infrared red (NIR) light irradiation and intradermal influenza vaccine and discovered the crucial role of reactive oxygen species (ROS) and mast cells. This study elucidates the effects of a new wavelength (1270 nm) of NIR light that exhibits a similar adjuvant effect at lower energy on mast cells and mouse skin, revealing ROS and ATP production via mitochondrial photoreception, increased chemokine mRNA expression, and durable antibody titers in immunized mice. These findings highlight the clinical potential of 1270 nm NIR light, demonstrating the wavelength-specific effect of laser adjuvants.

Photodynamic therapy is now recognized for an unique potential for use as a form of clinical cancer immunotherapy.

Investigating myeloid cells' role during cancer therapy is critical to developing novel strategies, as they shape the tumor microenvironment and modulate anti-tumor immune responses. Using single-cell RNA sequencing (scRNAseq), we examined the impact of the immunostimulant N-dihydrogalactochitosan (GC) on myeloid cells within MMTV-PyMT tumors. We discovered unique myeloid cell clusters with varied responses to GC, showing increased proportions of certain cell types, such as G-MDSC, monocytes, and DCs. Importantly, we observed significant upregulation of STING signaling-associated genes, indicative of conventional STING signaling and canonical NFkB signaling activation. Furthermore, our analysis showed an upregulation of proinflammatory cytokines in cDCs, and a significant reduction in M2-like macrophages post-GC treatment. This supports GC's potent immunostimulatory properties, activating key cells within the tumor microenvironment to enhance antitumor immunity.

Pancreatic cancer is one of the lethal types of cancer due to its ability to metastasize throughout the body. Despite recent advances in pancreatic cancer research, all the current cancer therapies have severe limitations in treating metastatic pancreatic cancer. Therefore, there is a need for a treatment regimen that can both break the immunosuppressive nature of the tumor and control cancer metastasis. We used a novel localized ablative immunotherapy, a combination of interstitial photothermal therapy (iPTT) and intratumoral administration of immunostimulant, to treat pancreatic tumors in mouse model. Here, we investigated the effects of iPTT on the tumor microenvironment or orthotopic mouse model to determine the optimal ablative effects. This treatment regimen will later be combined with an immunostimulant for a synergistic approach to provide an effective treatment modality for metastatic pancreatic cancers.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia which is considered to be a primary cause of treatment resistance observed in these tumors. Desmoplasia also plays a major role in mediating an immunosuppressive microenvironment and restricting immune cell infiltration in PDAC. In this study, using a syngeneic orthotopic immunocompetent KPC PDAC model, we demonstrate that PDT using Visudyne® can alter the tumor microenvironment, enhances immune cell infiltration, significantly reducing tumor growth and increasing survival in combination with anti-PD1.

Melanoma is the most serious kind of skin cancer. Circulating melanoma cells, the prognosis marker for metastasis, are present in the circulation at the early stage. Thus, quantitative detection of rare circulating melanoma cells is essential for monitoring tumor metastasis and prognosis evaluation. Compared with in vitro assays, in vivo flow cytometry is able to identify circulating tumor cells without drawing blood. Here, we have built in vivo photoacoustic flow cytometry based on the high absorption coefficient and monitoring circulating melanoma cells, which is useful for evaluating cancer stage and monitoring therapeutic effects.

T lymphocytes play a vital role in immune response, and as a result, their dysregulation is linked to numerous disease states. Imbalances of helper T cell subsets often precede symptomatic disease, indicating their potential as marker for disease detection and monitoring. Two-photon optical metabolic imaging (2P-OMI) offers advantages over conventional assays, as it can assess cellular metabolism on a single-cell level in a label-free manner. Preliminary data suggests 2P-OMI can identify helper T subtypes based solely on autofluorescence intensity and lifetime imaging of metabolic co-factors, potentially enabling rapid screening of patient immune cells to improve diagnoses and prognoses.

Intense research effort in low-temperature (or cold) atmospheric plasma application in bioengineering led to foundation of a new field, plasma medicine. Cold atmospheric plasmas (CAP) produce chemically reactive species including reactive oxygen species (ROS) and reactive nitrogen species (RNS). These species are known to have biological effects on prokaryotic and eukaryotic cells, such as the peroxidation of lipids and proteins. The most recent research area of plasma medicine is the interaction of CAP with cancer cells. It has been demonstrated by several investigators that CAP can induce apoptosis (programmed cell death) in various cancer cell lines. In addition, CAP treatment affects preferentially the cell cycle of cancer cells. This opened up the possibility that CAP could be the basis of a new cancer therapy. The uniqueness of low-temperature plasma is in its ability to change composition in situ. The above mentioned biomedical applications seem to usher a new transformational approach to healthcare based on CAP technology. In this presentation a review of the research achievements accomplished in the last decade will be presented.

Nanotheranostics combining photodynamic and photothermal therapies (PDT and PTT) with other therapeutic modalities has been shown to result in synergistically enhanced cancer treatment with minimal adverse effects. This talk will present our results on synergistically enhanced cancer phototheranostics delivered with tumor microenvironment or external stimuli responsive multifunctional nanoplatforms. Three different nanoplatforms involve protein nanocrystals, nanoliposomes and silica-based hybrid nanoparticles. All the nanoplatforms incorporate contrast agents for optical/multimodal imaging and therapeutic agents allowing to combine PDT/PTT with chemo and chemodynamic therapies. An application of these imaging guided nanoplatforms allowed us to achieve a synergistic combination of photodynamic and/or photothermal therapies with chemo- and chemodynamic treatments, resulting in an efficient diagnostics and enhanced therapy of cancer cells in vitro and in animal model in vivo.

Localized ablative immunotherapy (LAIT) combines targeted photothermal therapy (PTT) and immunotherapy to ablate the primary tumor site using laser irradiation while inducing systemic and specific anti-tumor immune responses for the treatment of metastatic cancers. The therapeutic efficiency of LAIT synergized with nanomedicine has been proven to be safe and effective for cancer treatment. Here, graphene oxide (GO) is used as a light-absorbing agent to enhance the generation of heat caused by PTT and increase its tumoricidal effect. GO is also a nanocarrier for drug delivery of the immune-stimulating biopolymer N-dihydrogalactochitosan (GC). GC is an innovative and effective immunostimulant/adjuvant with surfactant properties that was used to functionalize GO nanosheets. This work was designed to determine the main properties of GO/GC nanoparticles (NPs) when used in combination with PTT. The therapeutic efficacy of the treatment is being assessed on a highly aggressive and poorly immunogenic pancreatic tumor model in mice. Overall, GO/GC shows promising properties as a stable, safe, and effective photothermal agent and immunostimulant for nano-ablative immunotherapy for cancer.

Meningeal lymphatic vessels (mLVs) have been confirmed to scavenge amyloid beta (Aβ) from brain and might been damaged early on by deleterious processes implicated in AD, which is considered as a novel target for Alzheimer’s disease (AD) treatment. However, whether modulation of mLVs in the early stage could delay pathological progression of AD remains unknown. In this study, based on the superficial distribution of mLVs in dura, a near-infrared light was utilized to modulate lymphatic drainage of 3-month AD mice, and the therapeutic effect and potential mechanism were investigated on the mice at 6 months of age. The results showed that light ameliorates cognitive deficits and AD-associated pathology of 6-month-old AD mice by preserving transport ability of mLVs since the early stage. This study provides a novel strategy for AD prevention and intervention via mLVs modulation in early time.