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Messenger RNA (mRNA) has drawn much attention in the medical field. Through various treatment approaches including protein replacement therapies, gene editing, and cell engineering, mRNA is becoming a potential therapeutic strategy for cancers. However, delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular uptake. Therefore, in addition to mRNA modification, efforts have been devoted to developing nanoparticles for mRNA delivery. In this review, we introduce four categories of nanoparticle platform systems: lipid, polymer, lipid-polymer hybrid, and protein/peptide-mediated nanoparticles, together with their roles in facilitating mRNA-based cancer immunotherapies. We also highlight promising treatment regimens and their clinical translation.
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Objective: To evaluate the anti-tumor activity of mouse multi-subtype heat shock protein/peptide (mHSP/P) vaccine in combination with a programmed death ligand 1 (PD-L1) inhibitor in mouse sarcoma. Methods: Immunohistochemical staining and en-zyme-linked immunosorbent assay (Elisa) was used to quantitatively identify the expression of heat shock proteins (HSP70, HSP90, Grp94) in the sarcoma cell line MCA207. From the protein suspension prepared, mHSP/P and Grp94/peptide (Grp94/P) sarcoma vac-cines were isolated using chromatography and were identified by Western blot (WB). Flow cytometry was used to determine their cy-totoxic effects. The levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) produced upon mHSP/P and Grp94/P stimulation were measured by Elisa. The effect of sarcoma vaccines on the growth and survival of sarcoma was evaluated in mice. The expression of PD-L1 on the surface of MCA207 sarcoma cells was evaluated by immunofluorescent staining. The effect of IFN-γ treatment on the expression of PD-L1 was determined by WB. Animal experiments explored the effects of PD-L1 inhibitor in combination with mHSP/P treatment on tumors. Results: Tumor tissue carries a variety of HSP subtypes (HSP70, HSP90, Grp94). We successfully isolated sarco-ma tissue-derived mHSP/P and Grp94/P tumor vaccines, which were identified by WB; flow cytometry analysis demonstrated their cy-totoxicity. The levels of IFN-γ and TNF-α cytokines upon mHSP/P stimulation were significantly higher than that observed upon Grp94/P stimulation (P<0.05). The expression of PD-L1 on the surface of sarcoma cells increased with IFN-γ treatment. Animal experiments demonstrated that PD-L1 inhibitor in combination with mHSP/P significantly increased the immune response against tumor (P<0.05). Conclusions: Tumor-derived mHSP/P and Grp94/P can be used as tumor vaccines in animal models. The mHSP/P can elicit a stronger anti-tumor immune response than Grp94/P. IFN-γ stimulates the expression of PD-L1 in sarcoma cells, which results in immune eva-sion. The PD-L1 inhibitor in combination with mHSP/P increased the anti-tumor effect in the tumor microenvironment.
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Dermcidin (DCD) was found in isolated human skin sweat glands with antimicrobial effect, and was defined as a kind of new small molecule antimicrobial peptide. It was a part of human sweat glands in the skin as the immune system's innate defense. With the studies of DCD, its extensive biological functions are gradually discovered. Since 2010, a number of studies have shown that DCD may be a new risk factor for atherosclerosis. And the role of DCD in ischemic heart disease has drawn increasing attention in particular its relationship with insulin secretion and glycemic control, nitric oxide (NO) synthesis and hypertension, platelet aggregation and acute myocardial infarction (AMI). In those experiments, it was also confirmed that aspirin had antagonistic and reverse effects on various biological functions of DCD. Further research on the role of DCD in cardiovascular and cerebrovascular diseases may lead to the prevention, early warning, prognosis evaluation and treatment breakthrough of cardiovascular and cerebrovascular events.
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Objective To assess the efficacy of using four kinds of proteins / peptides to distinguish the tuberculosis patients from healthy people. Methods A, B, C and D were used to represent four proteins /peptides with 1 060, 1 944, 2 081 and 3 954 of mass to charge ratio (m / z) in serum, respectively. Levels A, B, C and D in serum of 57 patients with tuberculosis and 30 healthy people were determined by using the surface-enhanced laser desorption-ionization time of flight mass spectrometry (SELDI-TOF-MS). Then the differences of levels of f A, B, C and D were anlyzed between tuberculosis patients and healthy people. The efficacy of distinguishing tuberculosis patient from healthy people were evaluated by using diagnostic test evaluation method. Results (1) The levels of A, B, C and D were 1 ± 11, 1 597 ± 3 102, 460 ± 765 and 1 208 ± 1 003 in tuberculosis patients, while they were 123 ± 201, 47 ± 98, 36 ± 93 and 397 ± 355 in healthy people. (2) The area under the receiver operator characteristic (ROC) curve was 0.644, 0.848, 0.735 and 0.810 respectively. The serum levels of A, B, C and D could be used to distinguish tuberculosis patient from healthy people and the cut-off values of A, B, C and D were ≤166, ≥318, ≥48 and ≥728, respectively. Conclusions B, C and D have better performances to distinguish tuberculosis patients from healthy people , which may be regarded as new promising candidate markers for diagnosis of tuberculosis.
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Objective To observe the antioxidant activities of whey protein peptides (WPP) in aged mice.Method The subacute aged model mice were made by neck back subcutaneous injection of D-galactose every day.Compared with VE as positive control,the mice were given three different doses of WPP,100,200,400 mg/(kg bw?d) respectively,the effect of WPP on the content of catalase (CAT),malondialdehyde (MDA),superoxide dismutase (SOD),glutathione peroxidase (GSH-PX)in serum,liver and brain were observed after 45 d.Results The CAT,SOD and GSH-PX activities in aged model group were significantly decreased,but MDA was significantly increased as compared to normal mice.While in the aged mice treated with WPP 200 and 400 mg/(kg bw?d),the activity of CAT,SOD and GSH-PX were significantly increased and the content of MDA significantly decreased as compared to aged mice.Conclusion WPP shows dose-dependant antioxidant effect in aged mice.