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Gather wisdom to overcome barriers: Well-designed nano-drug delivery systems for treating gliomas.

ABSTRACT: Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.

SUBMITTER: Cui J

PROVIDER: S-EPMC9069319 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Gather wisdom to overcome barriers: Well-designed nano-drug delivery systems for treating gliomas.

Cui Jiwei J Xu Yuanxin Y Tu Haiyan H Zhao Huacong H Wang Honglan H Di Liuqing L Wang Ruoning R

Acta pharmaceutica Sinica. B 20210814 3

Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) h ...[more]

PMID: 35530155

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Project description:Mammalian prion diseases are infectious neurodegenerative diseases caused by the self-templating form of the prion protein PrPSc. Much evidence supports the hypothesis that prions exist as a mixture of a dominant strain and minor prion strains. While it is known that prions can infect new species, the relative contribution of the dominant prion strain and minor strains in crossing the species barrier is unknown. We previously identified minor prion strains from a biologically cloned drowsy (DY) strain of hamster-adapted transmissible mink encephalopathy (TME). Here we show that these minor prion strains have increased infection efficiency to rabbit kidney epithelial cells that express hamster PrPC compared to the dominant strain DY TME. Using protein misfolding cyclic amplification (PMCA), we found that the dominant strain DY TME failed to convert mouse PrPC to PrPSc, even after several serial passages. In contrast, the minor prion strains isolated from biologically cloned DY TME robustly converted mouse PrPC to PrPSc in the first round of PMCA. This observation indicates that minor prion strains from the mutant spectra contribute to crossing the species barrier. Additionally, we found that the PMCA conversion efficiency for the minor prion strains tested was significantly different from each other and from the short-incubation period prion strain HY TME. This suggests that minor strain diversity may be greater than previously anticipated. These observations further expand our understanding of the mechanisms underlying the species barrier effect and has implications for assessing the zoonotic potential of prions.ImportancePrions from cattle with bovine spongiform encephalopathy have transmitted to humans, whereas scrapie from sheep and goats likely has not, suggesting that some prions can cross species barriers more easily than others. Prions are composed of a dominant strain and minor strains, and the contribution of each population to adapt to new replicative environments is unknown. Recently, minor prion strains were isolated from the biologically cloned prion strain DY TME, and these minor prion strains differed in properties from the dominant prion strain, DY TME. Here we found that these minor prion strains also differed in conversion efficiency and host range compared to the dominant strain DY TME. These novel findings provide evidence that minor prion strains contribute to interspecies transmission, underscoring the significance of minor strain components in important biological processes.

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Gather wisdom to overcome barriers: Well-designed nano-drug delivery systems for treating gliomas.

Publications

Gather wisdom to overcome barriers: Well-designed nano-drug delivery systems for treating gliomas.

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