Organ-selective drug delivery is expected to maximize the efficacy of various therapeutic modalities while minimizing their systemic toxicity. Lipid nanoparticles and polymersomes can direct the organ-selective delivery of mRNAs or gene editing machineries, but their delivery is limited to mostly liver, spleen, and lung. A platform that enables delivery to these and other target organs is urgently needed. Here, a library of glycocalyx-mimicking nanoparticles (GlyNPs) comprising five randomly combined sugar moieties is generated, and direct in vivo library screening is used to identify GlyNPs with preferential biodistribution in liver, spleen, lung, kidneys, heart, and brain. Each organ-targeting GlyNP hit show cellular tropism within the organ. Liver, kidney, and spleen-targeting GlyNP hits equipped with therapeutics effectively can alleviate the symptoms of acetaminophen-induced liver injury, cisplatin-induced kidney injury, and immune thrombocytopenia in mice, respectively. Furthermore, the differential organ targeting of GlyNP hits is influenced not by the protein corona but by the sugar moieties displayed on their surface. It is envisioned that the GlyNP-based platform may enable the organ- and cell-targeted delivery of therapeutic cargoes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/adma.202311283 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Glycocalyx-Mimicking Nanoparticles with Differential Organ Selectivity for Drug Delivery and Therapy.
Adv Mater
July 2024
Department of Biological Sciences, KAIST Institute of BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141, Republic of Korea.
Organ-selective drug delivery is expected to maximize the efficacy of various therapeutic modalities while minimizing their systemic toxicity. Lipid nanoparticles and polymersomes can direct the organ-selective delivery of mRNAs or gene editing machineries, but their delivery is limited to mostly liver, spleen, and lung. A platform that enables delivery to these and other target organs is urgently needed.
View Article and Find Full Text PDFAnti-inflammatory Glycocalyx-Mimicking Nanoparticles for Colitis Treatment: Construction and In Vivo Evaluation.
Angew Chem Int Ed Engl
August 2023
Department of Biological Sciences, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141, Republic of Korea.
Common medications for treating inflammatory bowel disease (IBD) have limited therapeutic efficacy and severe adverse effects. This underscores the urgent need for novel therapeutic approaches that can effectively target inflamed sites in the gastrointestinal tract upon oral administration, exerting potent therapeutic efficacy while minimizing systemic effects. Here, we report the construction and in vivo therapeutic evaluation of a library of anti-inflammatory glycocalyx-mimicking nanoparticles (designated GlyNPs) in a mouse model of IBD.
View Article and Find Full Text PDFSystematic Screening and Therapeutic Evaluation of Glyconanoparticles with Differential Cancer Affinities for Targeted Cancer Therapy.
Adv Mater
July 2022
Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141, Republic of Korea.
Cancer-targeting ligands used for nanomedicines have been limited mostly to antibodies, peptides, aptamers, and small molecules thus far. Here, a library of glycocalyx-mimicking nanoparticles as a platform to enable screening and identification of cancer-targeting nanomedicines is reported. Specifically, a library of 31 artificial glycopolymers composed of either homogeneous or heterogeneous display of five different sugar moieties (β-glucose, β-galactose, α-mannose, β-N-acetyl glucosamine, and β-N-acetyl galactosamine) is converted to a library of glyconanoparticles (GlyNPs).
View Article and Find Full Text PDFExploring and Controlling the Polymorphism in Supramolecular Assemblies of Carbohydrates and Proteins.
Acc Chem Res
April 2020
The State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200438, P. R. China.
In biology, polymorphism is a well-known phenomenon by which a discrete biomacromolecule can adopt multiple specific conformations in response to its environment. This term can be extended to the ability of biomacromolecules to pack into different ordered patterns. Thus, exploration and control of the polymorphism of biomacromolecules via supramolecular methods have been key steps in achieving bioinspired structures, developing bioinspired functional materials, and exploring the mechanisms of these self-assembly processes, which are models for more complex biological systems.
View Article and Find Full Text PDFGlycocalyx-Mimicking Nanoparticles Improve Anti-PD-L1 Cancer Immunotherapy through Reversion of Tumor-Associated Macrophages.
Biomacromolecules
June 2018
Department of Macromolecular Science, The State Key Laboratory of Molecular Engineering of Polymers , Fudan University, Shanghai , 200438 , China.
Immune checkpoint blockade by anti-PD-L1 monoclonal antibody (αPD-L1) has achieved unprecedented clinical benefits in certain cancers, whereas the therapeutic efficacy is often hindered by immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs), which leads to innate resistance to this approach. To improve checkpoint blockade efficacy, the amphiphilic diblock copolymers poly(mannopyranoside/galactopyranoside methacrylate)- block-polystyrene are prepared by RAFT polymerization, which are sequentially self-assembled into glycocalyx-mimicking nanoparticles (GNPs) to neutralize TAMs. It is shown that GNPs can be specifically internalized by TAMs via lectin receptors, which results in upregulation of immunostimulatory IL-12 and downregulation of immunosuppressive IL-10, arginase 1, and CCL22, indicating functional reversion of protumor TAMs toward antitumor phenotype.
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!