A manual controlled theranostic nanoplatform with real-time photoacoustic quantification of drug release for chemophotothermal therapy.

The development of intelligent nanodrug delivery systems that can visually guide the on-demand quantitative control of drug release has received extensive attention. Herein, two chemotherapeutic drugs, gallic acid and 5-fluorouracil, and Fe(III) were selected to prepare nanomedicine GF-Fe via polyphenol-metal self-assembly and infinite coordination of drug-metal. GF-Fe has good biocompatibility, photothermal properties and photoacoustic (PA) signals. When deferoxamine (DFO) was artificially applied and interacted with GF-Fe, GF-Fe began to disassemble, gallic acid and 5-fluorouracil were gradually released, while the PA signal of the nanomedicine decayed synchronously. Based on this, the relationship between the intensity of the PA signal and the drug release amount was established, so as to realize the precise quantitative control of the drug release in real-time under the guidance of PA imaging. Besides, the combined effect of the two therapeutic drugs in combination with photothermal therapy (PTT) can improve the therapeutic effect, resulting in significant superadditiveness. This nanoplatform constructed by facile synthesis provided good clinical translation potential for the implementation of precise multimodal combination therapy strategies for tumors.

Construction of Artificial Controllable Aggregation Trojan Horse-Like Nanoplatform for Enhanced NIR-II Photothermal Therapy.

Promoting the aggregation of nanoprobes at tumor sites and realizing precise imaging and treatment of tumors is still one of the important problems to be solved in the field of nanomedicine. Poly-2-phenylbenzobisthiazole (PB) is a novel conjugated polymer with good biocompatibility, excellent photothermal properties in the second near-infrared region (NIR-II), but poor water dispersibility. Herein, a novel self-assembly/polymerization two-in-one strategy was proposed to prepare a new family of poly-2-phenyl-benzobisthiazole-based nanoparticles. Because the hydrophobic polymer PB was well "camouflaged" in the hydrophilic polyphenol-metal networks, the prepared "Trojan horse-like" nanoparticle TF-PB exhibited good water dispersibility. Besides, TF-PB can play a role as a contrast agent for photoacoustic and magnetic resonance dual-modality imaging. When deferoxamine was artificially applied and interacted with TF-PB, the polyphenol-metal networks disintegrated and the hydrophobic material PB was exposed and started hydrophobic aggregation. Thus, it can be applied for precise enhanced photothermal therapy (PTT) in the NIR-II. Meanwhile, the aggregation process enabled non-invasive, fast, and accurate real-time monitoring by self-enhancing photoacoustic imaging. This work has realized the artificially controllable aggregation of photothermal materials in the tumor site, solved the limitations of traditional PTT, and also has good application prospects in clinical therapy.

Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorate collagen-induced arthritis via immunomodulatory T lymphocytes.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease for which there are currently no effective therapies. Although mesenchymal stem cells (MSCs) can prevent arthritis through immunomodulatory mechanisms, there are several associated risks. Alternatively, MSC-derived small extracellular vesicles (sEVs) can mimic the effects of MSCs, while reducing the risk of adverse events. However, few studies have examined sEVs in the context of RA. Here, we evaluate the immunomodulatory effects of human umbilical cord MSC (hUCMSC)-derived sEVs on T lymphocytes in a collagen-induced arthritis (CIA) rat model to elucidate the possible mechanism of sEVs in RA treatment. We then compare these mechanisms to those of MSCs and methotrexate (MTX). METHODS: The arthritis index and synovial pathology were assessed. T lymphocyte proliferation and apoptosis, Th17 and Treg proportions, and interleukin (IL)-17, IL-10, and transforming growth factor (TGF)-ß expression were detected using flow cytometry. Retinoic acid receptor-related orphan receptor gamma t (RORγt) and forkhead box P3 (FOXP3), which are master transcriptional regulators of Th17 and Treg differentiation, were also assessed using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: sEV treatment ameliorated arthritis and inhibited synovial hyperplasia in a dose-dependent manner. These effects were mediated by inhibiting T lymphocyte proliferation and promoting their apoptosis, while decreasing Th17 cell proportion and increasing that of Treg cells in the spleen, resulting in decreased serum IL-17, and enhanced IL-10 and TGF-ß expression. Transcriptionally, sEVs decreased RORγt and increased FOXP3 expression in the spleen, and decreased RORγt and FOXP3 expression in the joints. In some aspects sEVs were more effective than MSCs and MTX in treating CIA. CONCLUSIONS: hUCMSC-derived sEVs ameliorate CIA via immunomodulatory T lymphocytes, and might serve as a new therapy for RA.

Synovial membrane mesenchymal stem cells: past life, current situation, and application in bone and joint diseases.

Mesenchymal stem cells (MSCs) can be isolated from not only bone marrow, but also various adult mesenchymal tissues such as periosteum, skeletal muscle, and adipose tissue. MSCs from different tissue sources have different molecular phenotypes and differentiation potential. Synovial membrane (SM) is an important and highly specific component of synovial joints. Previous studies have suggested that the synovium is a structure with a few cell layers thick and consists mainly of fibroblast-like synoviocytes (FLS), which forms a layer that lining the synovial membrane on the joint cavity and synovial fluid through cell-cell contact. In recent years, studies have found that there are also mesenchymal stem cells in the synovium, and as an important part of the mesenchymal stem cell family, it has strong capabilities of cartilage forming and tissue repairing. This article reviews the sources, surface markers, subtypes, influencing factors, and applications in inflammatory joints of synovial membrane mesenchymal stem cells (SM-MSCs) in recent years, aiming to clarify the research status and existing problems of SM-MSCs.