Bioinspired yeast microcapsules loaded with self-assembled nanotherapies for targeted treatment of cardiovascular disease

Zhang, Xiangjun; Xu, Xiaoqiu; Chen, Yidan; Zhou, Xing; Li, Lanlan; Li, Chenwen; An, Huijie; Tao, Hui; Hu, Houyuan; Li, Xiaohui; Zhang, Jianxiang

doi:10.1016/j.mattod.2017.05.006

Cited by 77 publications

(57 citation statements)

References 60 publications

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“…In addition to the previous evidence of “macrophages in the gut-associated lymphatic tissue may traffic away from the gut and infiltrate other reticuloendothelial and mononuclear phagocyte system tissues 30 , 31 , 51 , 52 ”, we speculate that NPs-mediated gene regulation plays an important role in the treatment of PTOA in this study. To prove this hypothesis, simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) 32 were used to evaluate the mechanism of YCWP-NPs.…”

Section: Discussionsupporting

confidence: 72%

“…Evidence suggests that yeast was engulfed by gut-associated lymphatic tissue macrophages via oral route. And macrophages in the gut-associated lymphatic tissue may traffic away from the gut and infiltrate other reticuloendothelial and mononuclear phagocyte system tissues 30 , 31 , 51 , 52 . It has been reported that drugs mediated by yeast microcapsules can be used for atherosclerosis therapy via oral route 30 .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, yeast microcapsule has been shown to be resistant to digestion in the gastrointestinal tract and be used for nanomaterials, gene and protein delivery via oral route 23 , 28 - 31 . It has been reported that drugs mediated by yeast microcapsules can be used for atherosclerosis therapy via oral route 30 . Thus, these characteristics make yeast microcapsule a preferred delivery vehicle for disease treatment via oral route.…”

Section: Introductionmentioning

confidence: 99%

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Yeast Cell wall Particle mediated Nanotube-RNA delivery system loaded with miR365 Antagomir for Post-traumatic Osteoarthritis Therapy via Oral Route

Zhang¹,

Hang²,

Zhang³

et al. 2020

Theranostics

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Post-traumatic osteoarthritis (PTOA) is an acute injury-induced joint inflammation followed by a gradual degradation of articular cartilage. However, there is no FDA-approved Disease-Modifying Osteoarthritis Drug currently. Although gene therapy with microRNA can improve PTOA progression, there is no effective gene delivery vehicle for orally deliver therapeutics due to the harsh environment of the gastrointestinal tract. In this study, we investigated the effect of yeast cell wall particle (YCWP) mediated nanotube-RNA delivery system on PTOA therapy via oral route. Methods: Nontoxic and degradable AAT and miRNA365 antagomir was self-assembled into miR365 antagomir/AAT (NPs). Then NPs-YCWP oral drug delivery system was constructed by using NPs and non-pathogenic YCWP which can be specifically recognized by macrophages. Moreover, surgical destabilization of the medial meniscus induced PTOA mice model was established to evaluate the therapeutic effect of NPs-YCWP via oral route. Results: Compared with control group, NPs showed higher gene inhibition efficiency both in chondrogenic cell line and primary chondrocytes in vitro . Treatment of macrophages with fluorescently labeled NPs-YCWP, the results showed that NPs-YCWP was successfully engulfed by macrophages and participated in the regulation of gene expression in vitro . Under the protection of YCWP, miR365 antagomir/AAT passes through the gastrointestinal tract without degradation after oral administration. After NPs-YCWP therapy, the results of histological staining, gene and protein expression showed that miR365 antagomir/NPs-YCWP improved the symptom of PTOA. Conclusion: Here, we constructed a biodegradable drug delivery system based on non-pathogenic YCWP and nanotubes, which can be used for PTOA therapy via the oral route. It suggests a new gene therapy strategy with YCWP mediated oral nano drug delivery system may serve as a platform for joint degeneration treatment.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Yeast Cell wall Particle mediated Nanotube-RNA delivery system loaded with miR365 Antagomir for Post-traumatic Osteoarthritis Therapy via Oral Route

Zhang¹,

Hang²,

Zhang³

et al. 2020

Theranostics

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“…Compared to the traditional therapies, such as mesalamine, aspirin, and dexamethasone, treatment with Ac2‐26 has few side effects due to its ability to mimic or induce natural pathways mediating the resolution of inflammation. On the other hand, patient‐friendly oral delivery is highly preferred for treatment of gastrointestinal and chronic diseases, owing to its convenience, high patient compliance, desirable cost‐effectiveness, and good safety profile . However, there are still tremendous challenges in the design and development of translational nanovehicles for oral delivery of macromolecular therapeutics, although different nanotherapies have been developed for targeted treatment of IBD .…”

Section: Introductionmentioning

confidence: 99%

A Proresolving Peptide Nanotherapy for Site‐Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota

et al. 2019

Self Cite

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The incidence and prevalence of inflammatory bowel disease (IBD) increases steadily worldwide. There is an urgent need for effective and safe IBD therapies. Accelerated resolution of inflammation is a new strategy for the management of inflammatory diseases. For effective and safe IBD treatment, herein a smart nanotherapy (i.e. oxidation‐responsive nanoparticles containing a proresolving annexin A1‐mimetic peptide Ac2‐26, defined as AON) is developed, which can release packaged Ac2‐26, in response to highly expressed reactive oxygen species (ROS) at diseased sites. AON effectively protects Ac2‐26 from degradation in the enzyme‐rich environment of the gastrointestinal tract. By delivering this nanotherapy to the inflamed colons of mice with IBD, site‐specific release and accumulation of Ac2‐26 in response to high levels of ROS at the inflammatory sites are achieved. Mechanistically, the Ac2‐26‐containing, oxidation‐labile nanotherapy AON effectively decreases the expression of proinflammatory mediators, attenuates trafficking and infiltration of inflammatory cells, promotes efferocytosis of apoptotic neutrophils, and increases phenotypic switching of macrophages. Therapeutically, AON reduces symptoms of inflammation, accelerates intestinal mucosal wound healing, reshapes the gut microbiota composition, and increases short‐chain fatty acid production. Additionally, oral delivery of this nanomedicine shows excellent safety profile in a mouse model, conferring the confidence for further development of a targeted precision therapy for IBD and other inflammatory diseases.

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“…A murine macrophage cell line (RAW264.7), which can recognize the β‐glucans of YCs via its Dectin‐1 receptor, was used to evaluate the uptake of as‐prepared OVA@Al‐MOFs/YCs. At 6 h of incubation, the intracellular colocalization of green fluorescence (FITC‐YCs) and red fluorescence (LysoTracker‐stained endo/lysosomes) was clearly visible ( Figure a), indicating that the receptor‐targeted uptake of the packed YCs proceeded via an endo/lysosomal pathway, which is essential for the delivery and processing of antigens . Macrophage cells are known to endocytose large particles with diameters of 1–10 µm …”

Section: Resultsmentioning

confidence: 99%

Engineering a Nanoscale Al‐MOF‐Armored Antigen Carried by a “Trojan Horse”‐Like Platform for Oral Vaccination to Induce Potent and Long‐Lasting Immunity

Miao

Pan

Chen

et al. 2019

Adv Funct Materials

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Vaccination via the oral administration of an antigen faces many challenges, including gastrointestinal (GI) proteolysis and mucosal barriers. To limit GI proteolysis, a biomimetically mineralized aluminum-based metal-organic framework (Al-MOF) system that is resistant to ambient temperature and pH and can act synergistically as a delivery vehicle and an adjuvant is synthesized over a model antigen ovalbumin (OVA) to act as armor. To overcome mucosal barriers, a yeast-derived capsule is used to carry the Al-MOF-armored OVA as a "Trojan Horse"-like transport platform. In vitro experiments reveal that the mineralization of Al-MOFs forms an armor on OVA that protects against highly acidic and degradative GI conditions. However, the mineralized Al-MOFs can gradually disintegrate in a phosphate ioncontaining simulated intracellular fluid, slowly releasing their encapsulated OVA. In vivo studies reveal that the "Trojan Horse"-like transport platform specifically targets intestinal M cells, favoring the transepithelial transport of the Al-MOF-armored OVA, followed by subsequent endocytosis in local macrophages, ultimately accumulating in mesenteric lymph nodes, yielding long-lasting, high-levels of mucosal S-IgA and serum IgG antibodies. Such an engineered delivery platform may represent a promising strategy for the oral administration of prophylactic or therapeutic antigens for vaccination.

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Bioinspired yeast microcapsules loaded with self-assembled nanotherapies for targeted treatment of cardiovascular disease

Cited by 77 publications

References 60 publications

Yeast Cell wall Particle mediated Nanotube-RNA delivery system loaded with miR365 Antagomir for Post-traumatic Osteoarthritis Therapy via Oral Route

Yeast Cell wall Particle mediated Nanotube-RNA delivery system loaded with miR365 Antagomir for Post-traumatic Osteoarthritis Therapy via Oral Route

A Proresolving Peptide Nanotherapy for Site‐Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota

Engineering a Nanoscale Al‐MOF‐Armored Antigen Carried by a “Trojan Horse”‐Like Platform for Oral Vaccination to Induce Potent and Long‐Lasting Immunity

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