Background: Endoplasmic reticulum (ER) stress has been found to foster the escape of cancer cells from immune surveillance and upregulate PD-L1 expression. However, the underlying mechanisms are unknown. Methods: While analyzing the protein levels using immunofluorescence and Western blotting, the RNA levels were measured using qRT-PCR. Ten injection of exosomes into six-week-old nude mice was made through the tail vein once every other day in total. Results: The expression of certain ER stress markers such as PERK (PKR-like endoplasmic reticulum kinase), ATF6 (activating transcription factor 6), and GRP78 (glucose-regulated protein 78), was found to be upregulated in the oral squamous cell carcinoma (OSCC) tissues and related to poor overall survival. There is a positive relationship between the extent of ER stress-related proteins and a cluster of PD-L1 expression and macrophage infiltration among the OSCC tissues. Further, incubation with exosomes derived from ER-stressed HN4 cells (Exo-ER) was found to upregulate PD-L1 extents in macrophages in vitro and in vivo, and macrophage polarization toward the M2 subtype was promoted by upregulating PD-L1. Conclusions: ER stress causes OSCC cells to secrete exosomal PD-L1 and upregulates PD-L1 expression in macrophages to drive M2 macrophage polarization. The delineation of a new exosome-modulated mechanism was made for OSCC–macrophage crosstalk driving tumor development and to be examined for its therapeutic use. Graphical Exosomal PD-L1 secreted by ER-stressed OSCC cells promoted M2 macrophage polarization.

Nano drugs have attracted increased attention due to their unique mode of action that offers tumor-inhibiting effects. Therefore, we have previously explored functionalized and drug-loaded graphene-gold nanocomposites that induced cancer cell apoptosis. In the present study, we developed a combination of monoclonal P-glycoprotein (P-gp) antibodies, folic acid (FA) and miR-122-loaded gold nanoparticles on graphene nanocomposites (GGMPN), which promoted drug-resistant HepG2 cell apoptosis with drug targeting and controlled release properties. We also investigated related apoptosis proteins and apoptosis signal pathways by GGMPN treatment in vitro and in vivo. Moreover, we further demonstrated the inhibition of tumor growth and the apoptosis-inducing effect by means of GGMPN with a semiconductor laser in a xenograft tumor model. In conclusion, our results collectively suggested that GGMPN could serve as a novel therapeutic approach to control tumor cell apoptosis and growth.

Currently, graphene oxide has attracted growing attention as a drug delivery system due to its unique characteristics. Furthermore, utilization of microRNAs as biomarkers and therapeutic strategies would be particularly attractive because of their biological mechanisms and relatively low toxicity. Therefore, we have developed functionalized nanocompounds consisted of graphene oxide, quantum dots and microRNA, which induced cancer cells apoptosis along with targeted imaging. In the present study, we synthesized a kind of graphene-P-gp loaded with miR-122-InP@ZnS quantum dots nanocomposites (GPMQNs) that, in the presence of glutathione, provides controlled release of miR-122. The miR-122 actively targeted liver tumor cells and induced their apoptosis, including drug-resistant liver tumor cells. We also explored the near-infrared fluorescence and potential utility for targeting imaging of InP@ZnS quantum dots. To further understand the molecular mechanism of GPMQNs-induced apoptosis of drug-resistant HepG2/ADM hepatoma cells, the relevant apoptosis proteins and signal pathways were explored in vitro and in vivo. Furthermore, near-infrared GPMQNs, which exhibited reduced photon scattering and auto-fluorescence, were applied for tumor imaging in vivo to allow for deep tissue penetration and three-dimensional imaging. In conclusion, techniques using GPMQNs could provide a novel targeted treatment for liver cancer, which possessed properties of targeted imaging, low toxicity, and controlled release.

Verbascoside (VB) has attracted a great deal of attention due to ITS pharmacological properties. In our study, we synthesized a multifunctional verbascoside coated Ni nanoparticles (VB‐Ni). Transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) display the characteristics of VB‐Ni nanoparticles. Compared with VB, VB‐Ni has been proven to induce apoptosis and resist the growth of doxorubicin‐resistant K562 cells in vitro and in vivo. Thus, VB‐Ni nanoparticles can be thought of as an ideal mode of cancer treatment.

Nanoparticles, especially gold nanoparticles (AuNPs), have been shown to be an efficient carrier to deliver small RNAs into cancer cells. In this study, we used cysteamine-functionalized AuNPs to effectively deliver TGF-β1 siRNA into hepatoma HepG₂ cells in vitro and in vivo. We found that, compared with AuNPs-mediated NC siRNA (AuNP-siNC), AuNPs-delivered TGF-β1 siRNA (AuNP-siTGFβ1) efficiently decreased the level of TGF-β1, increased cell apoptosis, and significantly inhibited the proliferation of recipient tumour cells. Systemic administration of the AuNP-siTGFβ1 complexes into human HepG₂ xenografted mice likewise reduced TGF-β1 expression and downstream TGF-β1 signalling. Functionally, AuNP-siTGFβ1 strongly inhibited tumour growth and improved the survival rate of tumour-bearing mice compared with the control groups. In conclusion, our results demonstrate that the siRNA delivery system with AuNP described here appears to be a highly effective method to deliver RNAi therapeutics into tumour cells for oncotherapy.