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  • Li, Xueping  (3)
  • Yi, Kaikai  (3)
  • 1
    Online Resource
    Online Resource
    Phosphatidylcholine‐Engineered Exosomes for Enhanced Tumor Cell Uptake and Intracellular Antitumor Drug Delivery
    Wiley ; 2021
    In:  Macromolecular Bioscience Vol. 21, No. 8 ( 2021-08)
    Details
    In: Macromolecular Bioscience, Wiley, Vol. 21, No. 8 ( 2021-08)
    Abstract: Exosomes derived from non‐tumor cells hold great potential as drug delivery vehicles because of their good biosafety and natural transference of bioactive cargo between cells. However, compared to tumor‐derived exosomes, efficient delivery is limited by their weak interactions with tumor cells. It is essential to engineer exosomes that improve tumor cellular internalization efficiency. A simple and effective strategy to enhance tumor cell uptake by engineering the exosome membrane lipids can be established by drawing on the role of lipids in tumor exosomes interacting with tumor cells. Amphiphilic phosphatidylcholine (PC) molecules are inserted into the membrane lipid layer of reticulocyte‐derived exosomes (Exos) by simple incubation to construct PC‐engineered exosomes (PC‐Exos). It is demonstrated that PC‐Exos showed significantly enhanced tumor cell internalization and uptake rate compared to native Exos, up to a twofold increase. After therapeutic agent loading, PC‐Exos remarkably promotes intracellular drug or RNA accumulation in cancer cells, thus showing enhanced in vitro anti‐tumor activity. This work demonstrates the crucial role of engineering exosomal lipids in modulating cancer cellular uptake, which may shed light on the design of high‐efficiency exosome‐based drug delivery carriers.
    Type of Medium: Online Resource
    ISSN: 1616-5187 , 1616-5195
    URL: Issue
    URL: Article
    DOI: 10.1002/mabi.v21.8
    DOI: 10.1002/mabi.202100042
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2039130-4
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Blood exosomes-based targeted delivery of cPLA2 siRNA and metformin to modulate glioblastoma energy metabolism for tailoring personalized therapy
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. 11 ( 2022-11-02), p. 1871-1883
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. 11 ( 2022-11-02), p. 1871-1883
    Abstract: Targeting glioblastoma (GBM) energy metabolism through multiple metabolic pathways has emerged as an effective therapeutic approach. Dual inhibition of phospholipid and mitochondrial metabolism with cytoplasmic phospholipase A2 (cPLA2) knockdown and metformin treatment could be a potential strategy. However, the strategic prerequisite is to explore a carrier capable of co-delivering the therapeutic combination to cross the blood-brain barrier (BBB) and preferentially accumulate at the GBM site. Methods Blood exosomes (Exos) were selected as the combination delivery carriers. The cellular uptake of Exos and the therapeutic effects of the combination strategy were evaluated in primary GBM cells. In vivo GBM-targeted delivery efficiency and anti-GBM efficacy were tested in a patient-derived xenograft (PDX) model. Results Here, we showed that the Exos-mediated cPLA2 siRNA/metformin combined strategy could regulate GBM energy metabolism for personalized treatment. Genomic analysis and experiments showed that polymerase 1 and transcript release factor (PTRF, a biomarker of GBM) positively regulated the uptake of Exos by GBM cells, confirming the feasibility of the delivery strategy. Further, Exos could co-load cPLA2 siRNA (sicPLA2) and metformin and co-deliver them across the BBB and into GBM tissue. The mitochondrial energy metabolism of GBM was impaired with this combination treatment (Exos-Met/sicPLA2). In the PDX GBM model, systemic administration of Exos-Met/sicPLA2 reduced tumor growth and prolonged survival. Conclusions Our findings demonstrated that Exos-based combined delivery of sicPLA2 and metformin selectively targeted the GBM energy metabolism to achieve antitumor effects, showing its potential as a personalized therapy for GBM patients.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac071
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2094060-9
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  • 3
    Online Resource
    Online Resource
    Engineering Lipusu with lysophosphatidylcholine for improved tumor cellular uptake and anticancer efficacy
    Royal Society of Chemistry (RSC) ; 2022
    In:  Journal of Materials Chemistry B Vol. 10, No. 11 ( 2022), p. 1833-1842
    Details
    In: Journal of Materials Chemistry B, Royal Society of Chemistry (RSC), Vol. 10, No. 11 ( 2022), p. 1833-1842
    Abstract: Liposomes have been developed as drug delivery carriers to enhance the antitumor efficiency of therapeutic agents. Lipusu® (Lip), a paclitaxel (PTX) liposome, has been widely used in the treatment of breast cancer. Compared with PTX, Lip could change the biodistribution and reduce the systemic toxicity. However, there was no positive effect on the entry of PTX into tumor cells, and thus the therapeutic effect was not significantly improved. Therefore, it is meaningful to engineer Lip for improving tumor cellular uptake efficiency. Here, lysophosphatidylcholine (LPC)-engineered Lip (LPC-Lip) was constructed via inserting single chain lipid tails into liposomal lipid bilayers, which was realized by simple incubation. Compared with Lip, the better cellular uptake of liposomes modified with LPC resulted in enhanced cytotoxic activity of LPC-Lip in 4T1 cells. Furthermore, stronger tumor growth inhibition was observed in LPC-Lip treated 4T1 tumor-bearing mice without significant side effects. In conclusion, by modulating the lipid composition of Lip, the antitumor efficacy can be improved, and LPC engineered Lip may serve as a promising formulation of PTX for future cancer therapy.
    Type of Medium: Online Resource
    ISSN: 2050-750X , 2050-7518
    URL: Article
    DOI: 10.1039/D1TB02823E
    Language: English
    Publisher: Royal Society of Chemistry (RSC)
    Publication Date: 2022
    detail.hit.zdb_id: 2702241-9
    detail.hit.zdb_id: 2705149-3
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