ABSTRACT: Nanoparticles Destabilizing the Cell Membranes Triggered by NIR Light for NIR-II Fluorescence Bio-Imaging, Photodynamic Therapy, and Photo-Immunotherapy
Project description:Safe and efficient antibacterial materials are urgently needed to combat drug-resistant bacteria and biofilm-associated infections. The rational design of nanoparticles for flexible elimination of biofilms by alternative strategies remains challenging. Herein, we propose the fabrication of Janus-structured nanoparticles targeting extracellular polymeric substance to achieve dispersion or near-infrared (NIR) light-activated photothermal elimination of drug-resistant biofilms, respectively. Asymmetrical Janus-structured dextran-bismuth selenide (Dex-BSe) nanoparticles are fabricated by a facile strategy to exploit synergistic effects of both components. The biocompatible dextran domain with the maximum exposure endows the Janus nanoparticles with biofilm penetration, targeting, and dispersion functions. Interestingly, Janus Dex-BSe nanoparticles realize enhanced dispersal of biofilms over time compared with dextran nanoparticles while the underlying molecular mechanisms are further revealed by RNA-sequencing transcriptomics analysis. Alternatively, taking advantage of the preferential accumulation of nanoparticles at infection sites, the self-propelled active motion induced by the unique Janus structure enhances the photothermal killing effect under NIR light irradiation, thereby eradicating the biofilm. Given these favorable features, the antibiofilm activity of Janus Dex-BSe against methicillin-resistant Staphylococcus aureus (MRSA) was first validated in vitro. More importantly, the flexible application of Janus Dex-BSe nanoparticles for biofilm removal or NIR-triggered eradication in vivo was demonstrated by MRSA-infected mouse excisional wound model and abscess model, respectively. The currently developed Janus nanoplatform holds great promise for the efficient elimination of drug-resistant biofilms in diverse antibacterial scenarios.
Project description:we present an aggregation-induced emission (AIE) - bacteria hybrid bionic robot to address the above issues. This bionic robot is composed of a multifunctional AIE molecule, INX-2 and Escherichia coli Nissle 1917 (EcN), i.e. EcN@INX-2. The robot is characterized by NIR-II fluorescence emission with efficient photodynamic and photothermal effects and tumor targeting, which was realized by INX-2 and EcN respectively, EcN@INX-2 achieved in vivo multimodal imaging and therapy of the tumors through multiple mechanisms including the activation of anti-tumor immunity, photodynamic and photothermal therapy in CT26 tumor-bearing female mice.
Project description:We describe the novel synthesis Ag2S nanoparticles (NPs) by using a sonochemical method and reveal the effects of NIR irradiation on the enhancement of the production of collagen through NIR-emitting Ag2S NPs. We also synthesized Li-doped Ag2S NPs that exhibited significantly increased emission intensity because of their enhanced absorption ability in the UV - NIR region.
Project description:We developed a microscopy-based approach, which we name optical enrichment, to select cells displaying a particular CRISPR-induced phenotype by automated imaging-based computation, mark them by photo-activation of an expressed photo-activatable fluorescent protein, and then isolate the fluorescent cells using fluorescence-activated cell sorting (FACS). One proof-of-principle screen, a nuclear size screen, a FSC screen and a H2B-mGFP screen were performed to validate the method.
Project description:Interventions: After general anesthesia, prior to incision, ICG;NanoColl will be injected endoscopically around the tumor. During surgery, fluorescence imaging will be performed to visualize tumor border and lymph nodes.
Primary outcome(s): 1. Percentage of patients in whom SLN identification was possible using NIR fluorescence imaging
2. Percentage of patients in whom intraopertive detection of the tumor border was possible by NIR fluorescence imaging
Study Design: N/A: single arm study, Open (masking not used), N/A , unknown, Parallel
Project description:Acidic tumor microenvironment (TME)-evoked MRC nanoparticles (MRC NPs) co-delivering immune agonist RGX-104 and photosensitizer chlorine e6 (Ce6) are reported for pyroptosis-mediated immunotherapy. RGX-104 remodels TME by transcriptional activation of ApoE to regress myeloid-derived suppressor cells’ (MDSCs) activity, which neatly creates foreshadowing for intensifying pyroptosis. Considering Ce6-triggered photodynamic therapy (PDT) can strengthen oxidative stress and organelles destruction to increase immunogenicity, immunomodulatory-photodynamic MRC nanodrugs will implement an aforementioned two-pronged strategy to enhance gasdermin E (GSDME)-dependent pyroptosis. RNA-seq analysis of MRC at the cellular level is introduced to first elucidate the intimate relationship between RGX-104 acting on LXR/ApoE axis and pyroptosis, where RGX-104 provides the prerequisite for pyroptosis participating in antitumor therapy. Briefly, MRC with favorable biocompatibility tackles the obstacle of hydrophobic drugs delivery, and becomes a powerful pyroptosis inducer to reinforce immune efficacy. MRC-elicited pyroptosis in combination with anti-PD-1 blockade therapy boosts immune response in solid tumors, successfully arresting invasive metastasis and extending survival based on remarkable antitumor immunity. MRC may initiate a new window for immuno-photo pyroptosis stimulators augmenting pyroptosis-based immunotherapy. Owing to the transcriptome sequencing on 4T1 cells exposed to various treatment, pyroptosis mechanism of MRC was thoroughly analyzed via comparing the expression discrepancy among PBS, MRC, and MRC+L groups.
Project description:Two-dimensional (2D) molybdenum disulfide (MoS2) nanomaterials are an emerging class of biomaterials that are photo-responsive at near-infrared wavelengths (NIR). Here, we demonstrate for the first time the ability of 2D MoS2 to modulate cellular functions of human stem cells through photothermal mechanisms. The interaction of MoS2 with human stem cells is investigated using whole transcriptome sequencing (RNA-seq). Global gene expression profile of stem cells reveals significant influence by NIR stimulation of MoS2 on integrins, cellular migration and wound healing. Overall, the combination of MoS2 and NIR light may provide new approach to control and regulate cellular migration and functions.
Project description:Polydopamine (PDA) is a polymer obtained from the self-polymerization of dopamine monomers; during the synthesis process, spherical nanoparticles are formed (PDA NPs), presenting several interesting properties such as high drug encapsulation capacity, easy and versatile surface modification, ability to convert near-infrared radiation (NIR) into heat, and strong antioxidant properties. In this work, PDA NPs have been proposed as an anti-cancer tool through the combination of NIR-mediated hyperthermia loading with a chemotherapeutic agent, sorafenib (SRF), specifically effective on liver cancer. Cell membranes isolated from hepatocarcinoma cancer cells (HepG2) have been exploited for the coating of the nanoparticles (thus obtaining CM-SRF-PDA NPs), in order to achieve homotypic targeting. The selective targeting capacity, photothermal, and chemotherapeutic activity of CM-SRF-PDA NPs have been evaluated on cell cultures in static and dynamic conditions, besides on 3D culture models. Eventually, the therapeutic effectiveness of the proposed approach has also been tested ex-ovo on a HepG2 spheroids-grafted chorioallantoic membrane model of quail embryos. This comprehensive investigation, supported by proteomic analysis, strongly suggest the developed nanoplatform for further pre-clinical investigations in the treatment of liver cancer.
Project description:Human hepatocellular carcinoma cells were subcutaneously implanted into nude mice and treated with photodynamic nanoparticles (NP3) with laser, followed by tissue collection and proteomic analysis.