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Osteosarcoma, a prevalent primary bone cancer in children, exhibits a poor prognosis due to the high prevalence of drug resistance. The objective of this study was to investigate the potential of fluorescent ultrafine polyethylenimine-coated caged platinum nanoclusters (PEI-Pt NCs) as an antitumor agent in osteosarcoma. The primary focus of this study involved the utilization of osteosarcoma cells (U2-OS and MG-63) and normal control cells (hBMSC) as the primary subjects of investigation. The capacity of PEI-Pt NCs to enter osteosarcoma cells was observed through the implementation of confocal microscopy. The impact of PEI-Pt NCs on migration and proliferation was assessed through the utilization of various methodologies, including the CCK8 assay, Ki-67 immunofluorescence, clone formation assay, transwell assay, and wound healing assay. Furthermore, the influence of PEI-Pt NCs on apoptosis and its underlying mechanism was explored through the implementation of flow cytometry and Western blotting techniques. The PEI-Pt NCs demonstrated the capability to enter osteosarcoma cells, including the nucleus, while also exhibiting fluorescent labeling properties. Furthermore, the PEI-Pt NCs effectively impeded the migration and proliferation of osteosarcoma cells. Additionally, the PEI-Pt NCs facilitated apoptosis by modulating the BAX-Bcl-2/Caspase 3/PARP axis. The novel nanomaterial PEI-Pt NCs possess diverse advantageous capabilities, including the ability to impede cell proliferation and migration, as well as the capacity to modulate the BAX-Bcl-2/Caspase 3/PARP axis, thereby promoting cell apoptosis. Consequently, this nanomaterial exhibits promising potential in addressing the issue of inadequate platinum-based treatment for osteosarcoma.

The contribution of type II alveolar epithelial stem cells (AEC II) to radiation-induced lung fibrosis (RILF) is largely unknown. Cell differentiation phenotypes are determined by the balance between Lin28 and lethal-7 microRNA (let-7 miRNA). Lin28 is activated by β-catenin. The aim of this study was to track AEC II phenotypes at different phases of injury following thoracic irradiation and examine the expression of β-catenin, Lin28 and let-7 to identify their role in AEC II differentiation. Results showed that coexpression of prosurfactant protein C (proSP-C, an AEC II biomarker) and HOPX (homeobox only protein X, an AEC I biomarker) or vimentin (a differentiation marker) was detected in AEC II post-irradiation. The protein expression levels of HOPX and proSP-C were significantly downregulated, but vimentin was significantly upregulated following irradiation. The expression of E-cadherin, which prevents β-catenin from translocating to the nucleus, was downregulated, and the expression of β-catenin and Lin28 was upregulated after irradiation (P < 0.05 to P < 0.001). Four let-7 miRNA members (a, b, c and d) were upregulated in irradiated lungs (P < 0.05 to P < 0.001), but let-7d was significantly downregulated at 5 and 6 months (P < 0.001). The ratios of Lin28 to four let-7 members were low during the early phase of injury and were slightly higher after 2 months. Intriguingly, the Lin28/let-7d ratio was strikingly increased after 4 months. We concluded that β-catenin contributed to RILF by promoting Lin28 expression, which increased the number of AEC II and the transcription of profibrotic molecules. In this study, the downregulation of let-7d miRNA by Lin28 resulted in the inability of AEC II to differentiate into type I alveolar epithelial cells (AEC I).

Platinum (Pt)-based chemotherapy drugs such as cisplatin are the first line and core options for the treatment of ovarian cancer (OC), while cisplatin resistance has a worse prognosis and low 5 year survival rate for patients. Chemotherapeutic drugs synthesized from nanomaterials have shown great potential in biomedicine; however, research into their application for OC resistance is rarely discussed. This study is proposed to elucidate the anti-tumor effects of polyethylenimine (PEI)-caged platinum nanoclusters (Pt NCs) on cisplatin-resistant OC. The results of confocal microscopy showed that Pt NCs entered cisplatin-resistant OC cells dose-dependently and aggregated both in the cytoplasm and inside the nucleus. Subsequently, according to the results of CCK8 assay, wound healing assay, clone formation assay, Transwell assay, Ki-67 immunofluorescence assay, and flow cytometry assay, the proliferation and migration of cisplatin-resistant OC cells were inhibited by Pt NCs, as well as their apoptosis was promoted. In addition, we validated the anti-tumor effect of Pt NCs on regulating autophagy via monodansylcadaverine (MDC) staining, transmission electron microscopy observation of the autophagic ultrastructure, LC3-II-GFP and P62-GFP adenovirus single-label immunofluorescence, and western blotting; meanwhile, the role of Pt NCs in adjusting autophagy through modulation of the PI3K-AKT-mTOR signaling was verified. Based on these results, it appears that cisplatin-resistant OC cells can undergo apoptosis when Pt NCs activate autophagy by inhibiting the PI3K/AKT/mTOR pathway, exhibiting a promising potential of Pt NCs in the development of a novel chemotherapeutic agent for patients suffering from cisplatin-resistant OC.