ABSTRACT
Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.
ABSTRACT
Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) is well-known as one of the main challenges for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart the drug efficacy. Herein, a therapeutic nanosystem (SPP-ARV-825) is constructed by incorporating the BRD4-degrading proteolytic targeting chimera (PROTAC) ARV-825 into the complex micelle (SPP) composed of substance P (SP) peptide-modified poly(ethylene glycol)-poly(d,l-lactic acid)(SP-PEG-PDLLA) and methoxy poly(ethylene glycol)-poly(d,l-lactic acid) (mPEG-PDLLA, PP), which could penetrate BBB and target brain tumor. Subsequently, released drug engenders antitumor effect via attenuating cells proliferation, inducing cells apoptosis and suppressing M2 macrophages polarization through the inhibition of IRF4 promoter transcription and phosphorylation of STAT6, STAT3 and AKT. Taken together, our work demonstrates the versatile role and therapeutic efficacy of SPP-ARV-825 micelle against glioma, which may provide a novel strategy for glioma therapy in future.
ABSTRACT
Objective To develop SPE - HPLC method for the assay of paeonol in Liuwei Dihuang Pill (LDP). Methods Separation was performed on a Hypersil ODS(2) column (250 mm?4. 6 mm, 5?m) . The mobile phase consist of methanol - 2 % acetic acid (55 :45, v/v) . The flow rate was 1 mL/min. The UV detection was set at 275 nm. Results Paeonol had a good linear relation in the range of 0. 03998 ~ 0. 7996 ug, the average recovery of honeyed bolus of LDP was 102. 9 % and the RSD was 1.2%; the average recovery of concentrated bolus of LDP was 101. 5 % and the RSD was 1.8%. Conclusion The method is simple, sensitive and rapid and it can be used to determine the paeonol content of LDP.
ABSTRACT
Objective: To provide an easy and feasible algorithm of the similarity between chromatographic fingerprints of herbs. Methods: To calculate similarity by combining the chromatographic overlap rate with relative area or height of mutual peaks of chromatographic fingerprints. Results: The algorithm was applied to the chromatographic fingerprints of samples in two references and the result is consistent with the fact. Conclusion: The calculated similarity with the proposed method can be sensitive to indicate the difference between fingerprints of herbs and the provided algorithm is simple and easy to be used.