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The combination of an antigen and adjuvant has synergistic effects on an immune response. Coadministration of an antigen and a granulocyte-macrophage colony-stimulating factor (GM-CSF) hydrogel delivery system will afford a novel strategy for enhancement of an immune response because of the dual role of the hydrogel as a vaccine carrier with a sustained release and a platform for recruiting dendritic cells (DCs). Herein, an injectable poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) thermosensitive hydrogel coencapsulating GM-CSF and ovalbumin nanoparticles was developed to enhance antigen uptake efficiency. The GM-CSF released from the hydrogel ensured accumulation of DCs; this effect improved the antigen uptake efficiency with the targeted delivery to antigen-presenting cells. Furthermore, the dual delivery system induced a stronger immune effect, including higher CD8 T proportion, interferon γ secretion, and a greater cytotoxic T lymphocyte response, which may benefit from the recruitment of DCs, increasing antigen residence time, and the controllable antigen release owing to the combined effect of the hydrogel and nanoparticles. Meanwhile, the real-time antigen delivery process in vivo was revealed by a noninvasive fluorescence imaging method. All of the results indicated that the visible dual delivery system may have a greater potential for the efficient and trackable vaccine delivery.

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The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) indicates poor prognosis and promotes EMT and metastasis. EMT, a crucial cellular process that occurs during cancer progression and metastasis, has been reported to promote drug resistance in several previous studies. Consequently, ongoing research has been focused on exploring therapeutic options for preventing EMT to delay or reverse drug resistance. Polyphyllin I (PPI) is a natural component extracted from Paris polyphylla that displays anti-cancer properties. In the present study, we investigated whether PPI can be used in the cisplatin (DDP)-resistant human gastric cancer cell line SGC7901/DDP. The results demonstrated that PPI treatment significantly inhibited cell proliferation, invasion and EMT. TGF-β1 is known to promote EMT-induced metastasis in numerous tumor types. PPI inhibited the invasion of TGFβ1-induced SGC7901/DDP cells in vitro. PPI also increased the mRNA and protein expression levels of E-cadherin but decreased the expression levels of vimentin. Further examination of the mechanism revealed that the CIP2A/PP2A/Akt pathway is partially involved in this regulation of EMT-related biomarkers and invasion. Furthermore, xenograft tests also confirmed the antitumor effects of PPI in vivo. We propose that PPI could be developed as a candidate drug for treating cancer invasion and migration.

Photodynamic therapy (PDT) is promising for clinical cancer therapy; however, the efficacy was limited as an individual treatment regimen. Here, an approach synergistically combining PDT and nitric oxide (NO) gas therapy along with destruction of the tumor extracellular matrix (ECM) was presented to eliminate cancer. Specifically, the NO donor L-arginine (L-Arg) and the photosensitizer indocyanine green (ICG) were co-encapsulated in poly(lactic-glycolic acid) (PLGA) nanoparticles and then loaded into the poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL−PEG−PCL) hydrogel to develop an injectable, thermosensitive dual drug delivery system