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All-in-one Engineering Multifunctional Nanoplatforms for Sensitizing Tumor Low-Temperature Photothermal Therapy in vivo

ABSTRACT: To determine the effects of photothermal therapy on regulatory genes and molecular pathways of mouse triple negative breast cancer cells (4T1 cells), we studied the RNA sequences of 4T1 cells treated with medium (control), MoS2 NPs and MoS2 NPs + NIR (808 nm).

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE244922 | GEO | 2023/10/11

REPOSITORIES: GEO

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Photothermal Modulation of Human Stem Cells Using Light-responsive 2D Nanomaterials

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RNA-Seq-guided triple-combination nano-system of gold nanocluster, quercetin, and docetaxel for ultimate synergistic photothermal-chemotherapy against MDR tumor

Project description:For oncological purposes, hyperthermia has increasingly emerged as a good therapeutic option for patients without fitness to undergo surgery, or for those with surgically inaccessible tumors. However, tumor recurrence after photothermal therapy constitutes a significant barrier to achieving good survival outcome. In this study, we used a gold nanocluster (GNC) micelle system capable of multiple NIR laser exposure; RNA-seq analysis revealed that repeated NIR exposure upregulates heat-shock protein and cell-cycle process-related genes that could be associated with tumor recurrence. To prevent recurrence, we presented an RNA-seq-guided drug combination strategy of GNC, docetaxel, and quercetin via a nano-system. Quercetin treatment downregulated heat-shock protein expression and inhibited function of P-gp with mild antitumor activity. Furthermore, docetaxel treatment demonstrated antitumor activity with significant G2-M cell-cycle arrest. When two of GNC, docetaxel, and quercetin were administered together, they showed a synergistic antitumor effect, whereas when the drugs were administered simultaneously in a triple combination, a very strong synergistic effect was achieved, as indicated through increased apoptosis induction and cell-cycle arrest in vitro and in vivo. The data from this study emphasize the benefit of triple combination and outlines potential translational directions for photothermal-chemotherapy.

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Polydopamine nanoparticles-based hyperthermal chemotherapy for the treatment of liver cancer

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.

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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.

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Photothermal Modulation of Human Stem Cells Using Light-responsive 2D Nanomaterials

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A Role for the RNA-Binding Protein MOS2 in MicroRNA Maturation in Arabidopsis

Project description:microRNAs (miRNAs) play important roles in the regulation of gene expression. In Arabidopsis, mature miRNAs are processed from primary miRNA transcripts (pri-miRNAs) by nuclear HYL1/SE/DCL1 complexes that form Dicing bodies (D-bodies). Here we report that a RNA-binding protein MOS2 bound to pri-miRNAs and was required for their efficient processing. MOS2 did not interact with HYL1, SE, and DCL1 and was not localized in D-bodies. Interestingly, in the absence of MOS2, the recruitment of pri-miRNAs by HYL1 was greatly reduced and the localization of HYL1 in D-bodies was compromised. These data suggest that MOS2 facilitates pri-miRNA processing through facilitating the recruitment of pri-miRNAs by the Dicing complexes. Examination of gene expression profiles in Col-0 and mos2-2 plants by deep sequencing

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