Inspired by the amino acid composition of natural protein surfaces, we developed a zwitterionic cloak containing multi-layers of short alternating glutamic acid and lysine (EK) peptides as a facile, highly effective and low-immunogenicity approach for the protection and delivery of biotherapeutics. Each EK layer grafted to proteins provides multiple times of new lysine reaction sites for the growth of subsequent EK layers. This unique design allows EK peptides to achieve high coating density on proteins, overcoming the limitation of traditional conjugation strategies that rely on the number of innate lysine groups. A triple-layer EK cloak manifests to successfully eliminate the specific and non-specific interactions of protected asparaginase with biological media while prolong the drug circulation time and significantly mitigate its immunogenicity in vivo, suggesting an EK peptide cloak as a promising approach to improve the safety and efficacy of biotherapeutics.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/anie.202004995 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Poxin-deficient poxviruses are sensed by cGAS prior to genome replication.
J Gen Virol
October 2024
Department of Microbial Sciences, University of Surrey, Guildford, GU2 7XH, UK.
Poxviruses are dsDNA viruses infecting a wide range of cell types, where they need to contend with multiple host antiviral pathways, including DNA and RNA sensing. Accordingly, poxviruses encode a variety of immune antagonists, most of which are expressed early during infection from within virus cores before uncoating and genome release take place. Amongst these antagonists, the poxvirus immune nuclease (poxin) counteracts the cyclic 2'3'-GMP-AMP (2'3'-cGAMP) synthase (cGAS)/stimulator of interferon genes DNA sensing pathway by degrading the immunomodulatory cyclic dinucleotide 2'3'-cGAMP, the product of activated cGAS.
View Article and Find Full Text PDFBrain targeted biomimetic siRNA nanoparticles for drug resistance glioblastoma treatment.
J Control Release
December 2024
Department of Radiotherapy and Translational Medicine Center, Huaihe Hospital of Henan University, Henan University, Kaifeng, Henan 475004, China; Henan-Macquarie Uni Joint Centre for Biomedical Innovation, Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, Henan International Joint Laboratory of Nanobiomedicine, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China. Electronic address:
Glioblastoma multiforme (GBM), the most aggressive intracranial neoplasm, remains incurable at present, primarily due to drug resistance, which significantly contributes to elevated recurrence rates and dismal prognosis. Signal transducer and activator of transcription 3 (STAT3) is a critical gene closely associated with GBM drug resistance and the progression of GBM stem cells (GSCs), making it a promising therapeutic target. In this study, we developed cancer cell membrane-cloaked biomimetic nanoparticles to deliver STAT3 siRNA to reverse drug resistance in homologous GBM.
View Article and Find Full Text PDFNanoenabled IL-15 Superagonist via Conditionally Stabilized Protein-Protein Interactions Eradicates Solid Tumors by Precise Immunomodulation.
J Am Chem Soc
November 2024
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Protein complexes are crucial structures that control many biological processes. Harnessing these structures could be valuable for therapeutic therapy. However, their instability and short lifespans need to be addressed for effective use.
View Article and Find Full Text PDFTwo-pronged anti-cancer nanovaccines enpowered by exogenous/endogenous tumor-associated antigens.
J Control Release
September 2024
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou 215123, China. Electronic address:
Cancer vaccines based on single-source (exogenous or endogenous) tumor-associated antigens (TAAs) are often challenged by the insufficient T cell response and the immunosuppressive tumor microenvironment (TME). Herein, a dual TAAs-boosted nanovaccine based on cancer cell (4T1) membrane-cloaked, CO-immobilized Prussian blue nanoparticles (4T1-PB-CO NPs) is developed and coupled with anti-interleukin (IL)-10 therapy to maximize the efficacy of antitumor immunotherapy. 4T1 cell membrane not only endows NPs with tumor targeting ability, but also serves as exogenous TAAs to trigger CD4 T cell response and M1-phenotype polarization of tumor-associated macrophages.
View Article and Find Full Text PDFMacrophage membrane-reversibly camouflaged nanotherapeutics accelerate fracture healing by fostering MSCs recruitment and osteogenic differentiation.
J Nanobiotechnology
July 2024
Department of Gastroenterology, The Second Affiliated Hospital, Soochow University, Suzhou, 215004, China.
The fracture healing outcome is largely dependent on the quantities as well as osteogenic differentiation capacities of mesenchymal stem cells (MSCs) at the lesion site. Herein, macrophage membrane (MM)-reversibly cloaked nanocomplexes (NCs) are engineered for the lesion-targeted and hierarchical co-delivery of short stromal derived factor-1α peptide (sSDF-1α) and Ckip-1 small interfering RNA (Ckip-1 siRNA, siCkip-1) to promote bone repair by concurrently fostering recruitment and osteogenic differentiation of endogenous MSCs. To construct the NCs, a membrane-penetrating α-helical polypeptide first assembles with siCkip-1, and the cationic NCs are sequentially coated with catalase and an outer shell of sSDF-1α-anchored MM.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!