Rationally designed nanostructured materials can produce improved drug carriers that play an increasingly important role in cancer treatment. In comparison with conventional drug combination approaches, using co-delivery systems of multiple drugs achieves sophisticated targeting strategies and multifunctionality. First, a nano-co-delivery of chitosan/tripolyphosphate (CS-TPP) was synthesized and characterized combining 5-aminolevulinic acid photodynamic therapy (ALA-PDT) with methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) shRNA. In this report, we investigated the efficacy of the simultaneous delivery of shRNA/photosensitizer on the gene expression of oral squamous cell carcinoma (OSCC) cells. The efficacy of CS-TPP-(shMTHFD1L-ALA)-PDT in inducing apoptosis and in generating of reactive oxygen species (ROS) in vitro was then assessed by Annexin V-PI and DCFH-DA assays respectively. In vivo therapeutic experiments were conducted in well-established orthotopic animal models of HNSCC. The results showed that the CS-TPP-(shMTHFD1L-ALA) nanoparticles (NPs) were approximately 145 nm in size. The cytotoxicity of OSCC cells was significantly increased by co-delivery of MTHFD1L shRNA and ALA-PDT compared with other groups. Furthermore, individual and combined therapies revealed remarkable pro-apoptotic, ROS and anti-tumorigenesis effects, and CS-TPP-(shMTHFD1L-ALA)-PDT had additive effects in vitro and in vivo. These observations indicate that CS-TPP-(shMTHFD1L-ALA) NPs may be an ideal candidate for gene/photosensitizer delivery.

Compared with mesenchymal stem cells (MSCs) obtained from other tissue sources, those derived from umbilical cord (UC) tissue exhibit numerous advantages and vast potential for therapeutic applications. However, MSCs from different tissue sources are heterogeneous, and therefore, the therapeutic efficacy of UC-derived MSCs as a replacement for other tissue-derived MSCs needs to be studied. To better understand the distinctions between UC-derived MSCs and MSCs derived from other tissues, we conducted a transcriptome analysis of MSCs obtained from UC and three other tissues. Correlation analysis revealed the strongest correlation between UC-MSCs (UC-MSCs) and bone marrow-MSCs (BM-MSCs). Compared with UC-MSCs, the lower differentially expressed genes of BM-MSCs, dental pulp-MSCs (DP-MSCs), and adipose tissue-MSCs (AP-MSCs) were predominantly enriched in actin-related terms, while higher differentially expressed genes were predominantly enriched in immunological processes. We also analyzed the distribution of 34 frequently or highly expressed cell characterization molecules in BM-MSCs, DP-MSCs, AP-MSCs, and UC-MSCs. CD200 (FPKM >10) was only detected in UC-MSCs, while CD106 was detected in AD-MSCs and DP-MSCs (FPKM >10). The reliability of transcriptomic data analysis was verified by quantitative real-time PCR. Finally, we recommend the use of CD200, CD106, and other similar markers with unstable expression as benchmark molecules to monitor the proliferation and differentiation potential of MSCs. This study provides comprehensive insights into the heterogeneity between UC-MSCs and MSCs derived from other tissues, which can guide the therapeutic application of UC-MSCs.

Oral squamous cell carcinoma (OSCC) can be characterized by severe functional impairment and a poor prognosis. The epidermal growth factor receptor (EGFR) is highly expressed in OSCC and is a promising target for cancer therapy. In addition, aminolevulinic acid-induced photodynamic therapy (ALA-PDT) has produced robust clinical effects in oral cancer. Here, an EGFR inhibitor, nimotuzumab, was administered to 2 OSCC cell lines, CAL-27 and SCC-25, treated with ALA-PDT. Cell growth, apoptosis, and reactive oxygen species (ROS) generation were used to measure the antitumor activity of the combination therapy. The in vivo effect of nimotuzumab plus ALA-PDT was done using a mouse OSCC xenograft model (SCC-25). EGFR expression was further compared by Western blotting in different groups. We observed that nimotuzumab combined with ALA-PDT could enhance inhibition of OSCC cell growth in vitro and in vivo. We also observed an enhanced effect after combination on cell apoptosis in CAL-27 and SCC-25 cells. Furthermore, combined therapy significantly reduced the protein expression levels of EGFR in vitro. However, we observed that nimotuzumab plus ALA-PDT did not increase ROS generation substantially in OSCC cells compared to the ALA-PDT group alone. These observations indicate that nimotuzumab combined with ALA-PDT has valuable applications for OSCC treatment.

Local electrical stimulation (LES) is a widely used clinical method to treat peripheral nerve injury. However, existing plate electrodes (PE) usually suffer from low electronic transport efficiency, whereas acupuncture electrical stimulation may cause damage to normal tissues. There is an urgent need to develop an innovative LES technique with efficient electronic transport, minimal tissue injury and enhanced biosafety. Here, we present a new stretchable transcutaneous electrical stimulation system (STESS) that integrates dissolvable conductive microneedles (DCMN) for optimal skin penetration and electronic transport, along with snake-like electrodes that offer superior flexibility, which can effectively penetrate the stratum corneum, enabling deep tissue electrostimulation with minimal injury. In vitro studies and 3D finite-element analysis demonstrate that the DCMN-based electrotherapy significantly enhances subcutaneous nerve stimulation compared to the conventional PE-based technique. By diminishing the electrical resistance of the stratum corneum, the DCMN-based electrotherapy has shown remarkable in vivo therapeutic efficacy in a rat facial nerve crush injury model. This will pave the way for innovative physiotherapeutic methodologies in the realm of neurological rehabilitation.