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Immunosuppression and immune tolerance lead tumor cells to evade immune system surveillance and weaken drug efficacy. The presence of various immunosuppressive cells in the tumor microenvironment, especially tumor-associated macrophages (TAMs), has been shown to be a driving force in tumor initiation and development. Reversion of the TAM phenotype is an effective way to induce a subsequent antitumor immune response. In this study, we developed baicalin-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles containing an antigenic peptide (Hgp 100 25-33 , Hgp) and a toll-like receptor 9 agonist (CpG). The nanoparticles were further coated with a galactose-inserted erythrocyte membrane, which actively targeted the TAMs. The TAM polarization and tumor treatment effectiveness of the nanoparticles were evaluated. The biomimetic nanoparticles showed enhanced cell uptake in vitro and targeted effects in vivo. In addition, compared with baicalin-loaded PLGA-NPs (B@NPs), the biomimetic nanoparticles, such as Hgp/B@NPs-CpG and NPs@RBC-Gala, significantly polarized the TAMs such that they changed from the M2 type to the M1 type both in vitro and in vivo. Subsequently, the infiltration of CD4 + T and CD8 + T cells into tumor sites after being induced by the biomimetic nanoparticles was greatly increased, which suggested a significant enhancement of the immune activation effect and T cell response. In addition, the activation of the T cells and induction of the CTL responses effectively suppressed melanoma tumor growth in vivo. In conclusion, the biomimetic nanoparticles effectively reversed the TAM phenotype from M2 to M1, which further improved the tumor immune microenvironment and promoted tumor immunotherapy. These results suggested that the TAM-targeted biomimetic drug delivery system had the potential to reverse the phenotypes of TAMs contributing to reverse the immunosuppressive tumor microenvironment and promote tumor treatment.

Ultraviolet A (UV-A) radiation is the main component of solar radiation and can elicit a wide range of biochemical responses in plants. In this study, the effects of UV-A radiation on the flavonoid content, composition, and bioactivity in postharvest Scutellaria baicalensis roots were investigated. The total flavonoid content in S. baicalensis roots under postharvest UV-A radiation increased in a time-dependent manner and reached its maximum value (183.64 g kg−1) on the fifth day. Compared with the control group, the contents of four main flavonoids—baicalin, baicalein, wogonoside, and wogonin increased by 1.68 times, 3.00 times, 2.07 times, and 1.57 times, respectively; and new chemicals including pectolinarigenin, puerarin, isokaempferide, and jaceosidin were detected after 5 d of UV-A radiation. In addition, extracts of S. baicalensis roots exposed to postharvest UV-A radiation showed stronger antioxidant and antibacterial activities than control root extracts. Further correlation analysis revealed that baicalin and baicalein contents in the roots of S. baicalensis after postharvest UV-A radiation were positively correlated with antioxidant activity, while the main flavonoids showed different correlations with various bacteria. These results suggest that the appropriate duration of postharvest UV-A radiation is an effective way to enhance bioactive compound contents and their bioactivities in S. baicalensis roots. • UPLC-MS/MS showed that 4 flavonoid compounds newly appeared after UV-A radiation. • The content of flavonoids was significantly increased by UV-A radiation. • The antioxidant and antimicrobial activities were enhanced by UV-A radiation. • The increase of bioactivity was correlated to the flavonoid profile change. [ABSTRACT FROM AUTHOR]

[Display omitted] Hepatocellular carcinoma (HCC) causes the immunosuppressive tumor microenvironment (TME) resistant to current immunotherapy. The immunogenic apoptosis (currently termed immunogenic cell death, ICD) of cancer cells may induce the adaptive immunity against tumors, thereby providing great potential for treating HCC. In this study, we have confirmed the potential of scutellarin (SCU, a flavonoid found in Erigeron breviscapus) for triggering ICD in HCC cells. To facilitate in vivo application of SCU for HCC immunotherapy, an aminoethyl anisamide-targeted polyethylene glycol-modified poly(lactide-co-glycolide) (PLGA-PEG-AEAA) was produced to facilitate SCU delivery in this study. The resultant nanoformulation (PLGA-PEG-AEAA.SCU) remarkably promoted blood circulation and tumor delivery in the orthotopic HCC mouse model. Consequently, PLGA-PEG-AEAA.SCU reversed the immune suppressive TME and achieved the immunotherapeutic efficacy, resulting in significantly longer survival of mice, without inducing toxicity. These findings uncover the ICD potential of SCU and provide a promising strategy for HCC immunotherapy. [ABSTRACT FROM AUTHOR]

Ultraviolet-A (UV-A) can affect plant secondary metabolism, but the flavonoid synthesis in Scutellaria baicalensis Georgi aerial parts in response to UV-A radiation was not clear. Therefore, the effects of UV-A radiation on flavonoid synthesis in S. baicalensis aerial parts were investigated in this study. The results showed that the total flavonoid content in aerial parts of S. baicalensis reached the maximum value (41.86 mg g−1) after 7 d of UV-A radiation. Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) analysis showed that the composition of flavonoids was not changed, but the contents of different components were changed according to High-Performance Liquid Chromatography (HPLC) analysis. Compared with the control treatment, the contents of scutellarin, baicalin and wogonoside were increased by 2.70-fold, 2.22-fold and 2.31-fold, respectively. However, scutellarein and baicalein decreased by 1.80-fold and 1.91-fold respectively. Meanwhile, UV-A radiation significantly increased the contents of nitric oxide (NO) and hydrogen peroxide (H 2 O 2), and enhanced the activities of Phenylalanine ammonia lyase (PAL), Cinnamic acid 4-hydroxylase (C4H), and 4-coumarate CoA ligase (4CL). In addition, the antioxidant activity of S. baicalensis aerial part extracts after UV-A radiation was stronger than that of the control treatment. Further correlation analysis showed that there was a significant correlation between total flavonoid content and NO, H 2 O 2 , PAL, C4H, and 4CL. The enhancement of the antioxidant activity of S. baicalensis aerial part extracts was significantly correlated with total flavonoid, baicalin, wogonin and scutellarin content. This study shows that UV-A radiation can be used as an effective and economic way to increase the flavonoid contents in S. baicalensis aerial parts and promote the antioxidant activity of its extracts. [Display omitted] • The composition of flavonoids did not change after UV-A radiation. • The content of flavonoids was significantly affected by UV-A radiation. • Signal molecules and key enzyme activities were increased by UV-A radiation. • The antioxidant activity was enhanced by UV-A radiation. • The increase in bioactivity was correlated with the flavonoid profile change. [ABSTRACT FROM AUTHOR]