Quantitative proteomic analysis of exosomes from umbilical cord mesenchymal stem cells and rat bone marrow stem cells.

Exosomes derived from mesenchymal stem cells (MSCs) have been used for cancer treatment, however, an in-depth analysis of the exosomal proteomes is lacking. In this manuscript, we use the diaPASEF (parallel accumulation serial fragmentation combined with the data-independent acquisition) method to quantify exosomes derived from human umbilical cord mesenchymal stem cells (UCMSCs) and rat bone marrow stem cells (BMSCs), resulting in identification of 4200 human proteins and 5362 rat proteins. Comparison of human exosomal proteins and total cellular proteins reveals that some proteins exist in the exosomes exclusively that can be served as potential markers for exosomes. Quantitative proteomic analysis of exosomes from different passages of BMSCs shows that the proteins involved in TGF-ß signaling pathway are regulated in abundance, which could be markers for the therapeutic ability of BMSC exosomes. Collectively, the data presented by this study can be a resource for further study of exosome research.

Bcl-2 hijacks the arsenic trioxide resistance in SH-SY5Y cells.

Aresenic trioxide (ATO) is proven to be active against leukaemia cells by inducing apoptosis and differentiation. Even though ATO could effectively induce remissions of leukaemia cells, the drug resistance was observed occasionally. To further dissect the mechanism of ATO resistance, we selected the ATO-resistant SH-SY5Y cells and found that Bcl-2 controlled the sensitivity of ATO in SH-SY5Y cells. We report that necroptosis, autophagy, NF-ƘB and MAPK signalling pathway are not involved in ATO-induced apoptosis. Moreover, the ATO-resistant cells showed distinct mitochondrial morphology compared with that of ATO-sensitive cells. Intriguingly, nude mice-bearing ATO-sensitive cells derived xenograft tumours are more sensitive to ATO treatment compared with that of ATO-resistant cells. These data demonstrate that cancer cells can acquire the ATO-resistance ability by increasing the Bcl-2 expression.

Cuproptosis: Mechanism and Application in Lymphoma.

The cell death field has profited from the increasing attention of the scientific community and has been shown to lie at the very basis of cancer initiation and progression. Cuproptosis is a recently proposed method of cell death in 2022, and it is different from any previously reported method. The principle is that copper ions lead to aggregation and instability of intracellular proteins. An increasing number of researchers are dedicated to enriching the mechanism of cuproptosis and exploring its relationship with cancer. Studies have found that intracellular copper levels have an impact on the occurrence and development of lymphoma. The complexity of lymphoma and the limitations of treatment necessitate in-depth studies of the disease. We will review the mechanism of cuproptosis and its potential in lymphoma therapy.

DSPE-PEG2000-methotrexate nanoparticles encapsulating phenobarbital sodium kill cancer cells by inducing pyroptosis.

Cancer is a life-threatening disease worldwide. Nanomedicine and nanodelivery systems are recently developed scientific field that employs specific materials in the nanoscale range to deliver drugs. Lipid-based nanoparticles are an ideal delivery system since they exhibit many advantages, including high bioavailability, self-assembly, formulation simplicity, and the ability to exhibit a plethora of physicochemical properties. Herein, we report that phenobarbital sodium can kill cancer cells by using the DSPE-PEG2000-methotrexate nanoparticle delivery system, which can target folate receptors that are usually overexpressed on a variety of cancer cells. The released phenobarbital then executes cancer cells by inducing pyroptosis. Results from our animal model further indicate that the nanomedicine of nanoparticle-encapsulated phenobarbital sodium is a promising anticancer therapy.

Targeted pH-responsive biomimetic nanoparticle-mediated starvation-enhanced chemodynamic therapy combined with chemotherapy for ovarian cancer treatment.

In recent years, the use of arsenic trioxide (ATO) in the context of ovarian cancer chemotherapy has attracted significant attention. However, ATO's limited biocompatibility and the occurrence of severe toxic side effects hinder its clinical application. A nanoparticle (NP) drug delivery system using ATO as a therapeutic agent is reported in this study. Achieving a synergistic effect by combining starvation therapy, chemodynamic therapy, and chemotherapy for the treatment of ovarian cancer was the ultimate goal of this system. This nanotechnology-based drug delivery system (NDDS) introduced arsenic-manganese complexes into cancer cells, leading to the subsequent release of lethal arsenic ions (As3+) and manganese ions (Mn2+). The acidic microenvironment of the tumor facilitated this process, and MR imaging offered real-time monitoring of the ATO dose distribution. Simultaneously, to produce reactive oxygen species that induced cell death through a Fenton-like reaction, Mn2+ exploited the surplus of hydrogen peroxide (H2O2) within tumor cells. Glucose oxidase-based starvation therapy further supported this mechanism, which restored H2O2 and lowered the cellular acidity. Consequently, this approach achieved self-enhanced chemodynamic therapy. Homologous targeting of the NPs was facilitated through the use of SKOV3 cell membranes that encapsulated the NPs. Hence, the use of a multimodal NDDS that integrated ATO delivery, therapy, and monitoring exhibited superior efficacy and biocompatibility compared with the nonspecific administration of ATO. This approach presents a novel concept for the diagnosis and treatment of ovarian cancer.

Cancer Cell-Mimicking Prussian Blue Nanoplatform for Synergistic Mild Photothermal/Chemotherapy via Heat Shock Protein Inhibition.

Combined mild-temperature photothermal/chemotherapy has emerged as a highly promising modality for tumor therapy. However, its therapeutic efficacy is drastically compromised by the heat-induced overexpression of heat shock proteins (HSPs) by the cells, which resist heat stress and apoptosis. The purpose of this study was to downregulate HSPs and enhance the mild-temperature photothermal/chemotherapy effect. In detail, the colon cancer cell membrane (CT26M)-camouflaged HSP90 inhibitor ganetespib and the chemotherapeutic agent doxorubicin (DOX)-coloaded hollow mesoporous Prussian blue (HMPB) nanoplatform (named PGDM) were designed for synergistic mild photothermal/chemotherapy via HSP inhibition. In addition to being a photothermal agent with a high efficiency of photothermal conversion (24.13%), HMPB offers a hollow hole that can be filled with drugs. Concurrently, the cancer cell membrane camouflaging enhances tumor accumulation through a homologous targeting mechanism and gives the nanoplatform the potential to evade the immune system. When exposed to NIR radiation, HMPB's photothermal action (44 °C) not only causes tumor cells to undergo apoptosis but also causes ganetespib to be released on demand. This inhibits the formation of HSP90, which enhances the mild photothermal/chemotherapy effect. The results confirmed that the combined treatment regimen of mild photothermal therapy (PTT) and chemotherapy showed a better therapeutic efficacy than the individual treatment methods. Therefore, this multimodal nanoparticle can advance the development of drugs for the treatment of malignancies, such as colon cancer, and has prospects for clinical application.