was that most nanoparticles do not have a sufficiently long blood half-life and cannot realize deep penetration in tumor tissue. Thus, recent progress in the development of strategies for mimicking or modulating cells offers a highly attractive alternative to drug delivery. [10-17] As natural immune cells and antigenpresenting cells, macrophages [18] have a long blood half-life and can specifically bind to tumor tissue. Therefore, applying macrophages in chemical drug delivery would lead to a significant increase in drug accumulation in tumors. Since macrophages can engulf foreign particles in nature, they can directly phagocytose drugs and then deliver drugs to tumors. [19] Thus, live macrophages may serve as drug carriers. To further increase the tumor-targeting ability of macrophages, they can be engineered with targeting ligands. [20] In addition, learning from red blood cell (RBC) membrane coating technology, [21-23] a macrophage cell membrane coating was developed and it resulted in enhanced tumor uptake of drugs. On the other hand, macrophages play an important role in modulating the tumor immune microenvironment. M1 macrophages inhibit tumor growth, while M2 macrophages promote tumor growth. Inhibition of M2 macrophages and repolarization of M2 macrophages to M1 macrophages are common strategies to treat solid tumors. Furthermore, since these macrophages express SIRPα on their surface, their phagocytic activity against CD47-expressing tumor cells is significantly affected by the CD47-SIRPα pathway. Therefore, blocking the CD47-SIRPα pathway can further enhance the anti-tumor efficacy of macrophages. Herein, to elucidate the importance of macrophages in tumor therapy (Figure 1), we will first discuss the role of macrophages in cancer immunotherapy, including the inhibition, depletion, and repolarization of tumor-associated macrophages (TAMs) and the blocking of the CD47-SIRPα pathway to enhance phagocytosis in tumor therapy. Then, based on the tumor targeting of M1 macrophages, we will discuss the applications of macrophages, macrophage-derived exosomes, and macrophage-coated NPs for drug delivery. We will thus offer a comprehensive understanding of functionalizing macrophages for tumor therapy. Macrophages play an important role in cancer development and metastasis. Proinflammatory M1 macrophages can phagocytose tumor cells, while antiinflammatory M2 macrophages such as tumor-associated macrophages (TAMs) promote tumor growth and invasion. Modulating the tumor immune microenvironment through engineering macrophages is efficacious in tumor therapy. M1 macrophages target cancerous cells and, therefore, can be used as drug carriers for tumor therapy. Herein, the strategies to engineer macrophages for cancer immunotherapy, such as inhibition of macrophage recruitment, depletion of TAMs, reprograming of TAMs, and blocking of the CD47-SIRPα pathway, are discussed. Further, the recent advances in drug delivery using M1 macrophages, macrophage-derived exosomes, and macrophage-membrane-coated nanoparticles are ela...

Lycium barbarum (L. barbarum) fruit or extract has been regarded as a superior-grade Chinese medicine, used to modulate body immunity and for anti-aging purposes. However, the underlying molecular mechanisms behind these effects remain unclear. In the present study, L. barbarum polysaccharides (LBPs), considered a major contributor of L. barbarum effects, were used to elucidate its mechanism of action by phenotypic and senescence associated-β-galactosidase (SA-β-gal) assays, evaluation of survival rates in vivo and expression profiling of genes related to the p53 signaling pathway in a zebrafish model. Zebrafish embryos were continuously exposed to various concentrations of LBPs (1.0, 2.0, 3.0 and 4.0 mg/ml) for 3 days. The results of fluorescent acridine orange and SA-β-gal staining indicated that cell apoptosis and senescence mainly occur in the head at 24 hours post fertilization (hpf) and 72 hpf. In addition, resistance to replicative senescence was observed at low doses of LBPs, especially at the 3.0 mg/ml concentration. Furthermore, the expression of genes that relate to aging, such as p53, p21 and Bax, was decreased, while that of Mdm2 and TERT genes was increased after treatment with LBPs. The results demonstrated that the effects of LBPs on cell apoptosis and aging might be mediated by the p53-mediated pathway.

Aim:The potential for topical delivery of meloxicam was investigated by examining its pharmacokinetic profiles in plasma and synovial fluid following oral and transdermal administration in Beagle dogs. Methods: The experiment was a two-period, crossover design using 6 Beagle dogs. Meloxicam tablets were administered orally at a dose of 0.31 mg/kg, and meloxicam gel was administered transdermally at a dose of 1.25 mg/kg. Drug concentrations in plasma and synovial fluid were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The pharmacokinetic parameters were calculated using the Topfit 2.0 program. Results: The pharmacokinetic results showed that AUC 0-t (23.9±8.26 µg·h·mL -1 ) in plasma after oral administration was significantly higher than after transdermal delivery (1.00±0.43 µg·h·mL -1 ). In contrast, the ratio of the average concentration in synovial fluid to that in plasma following transdermal administration was higher than that for an oral delivery. The synovial fluid concentration in the treated leg was much higher than that in the untreated leg, whereas the synovial fluid concentration in the untreated leg was similar to the plasma concentration. Conclusion: The high concentration ratio of synovial fluid to plasma indicates direct penetration of meloxicam following topical administration to the target tissue. This finding is further supported by the differences observed in meloxicam concentrations in synovial fluid in the treated and untreated joints at the same time point. Our results suggest that transdermal delivery of meloxicam is a promising method for decreasing its adverse systemic effects.

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