Ligand‐Installed Nanocarriers toward Precision Therapy

Advanced Materials, Journal Year: 2019, Volume and Issue: 32(13)

Published: July 28, 2019

Development of drug-delivery systems that selectively target neoplastic cells has been a major goal nanomedicine. One strategy for achieving this milestone is to install ligands on the surface nanocarriers enhance delivery tissues, as well internalization by cells, which improves accuracy, efficacy, and ultimately enhances patient outcomes. Herein, recent advances regarding development ligand-installed are introduced effect their design biological performance discussed. Besides academic achievements, progress in clinical trials presented, along with challenges faced these formulations. Lastly, future perspectives discussed, particular emphasis potential emerging precision therapies.

Language: Английский

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Exploration of the Sialic Acid World

Advances in carbohydrate chemistry and biochemistry, Journal Year: 2018, Volume and Issue: unknown, P. 1 - 213

Published: Jan. 1, 2018

Language: Английский

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Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells

Journal of Clinical Investigation, Journal Year: 2018, Volume and Issue: 128(11), P. 4912 - 4923

Published: Aug. 21, 2018

First-generation immune checkpoint inhibitors, including anti-CTLA-4 and anti-programmed death 1 (anti-PD-1) antibodies, have led to major clinical progress, yet resistance frequently leads treatment failure. Thus, new targets acting on T cells are needed. CD33-related sialic acid-binding immunoglobulin-like lectins (Siglecs) pattern-recognition receptors binding a range of sialoglycan ligands, which appear function as self-associated molecular patterns (SAMPs) that suppress autoimmune responses. Siglecs expressed at very low levels normal cells, these were not until recently considered interesting for cancer immunotherapy. Here, we show an upregulation Siglecs, Siglec-9, tumor-infiltrating from non-small cell lung (NSCLC), colorectal, ovarian patients. Siglec-9-expressing coexpressed several inhibitory receptors, PD-1. Targeting the sialoglycan-SAMP/Siglec pathway in vitro vivo resulted increased anticancer immunity. expression Siglec-9 NSCLC patients correlated with reduced survival, polymorphisms showed association risk developing colorectal cancer. Our data identify potential target improving activation

Language: Английский

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Sialic Acid Blockade Suppresses Tumor Growth by Enhancing T-cell–Mediated Tumor Immunity

Cancer Research, Journal Year: 2018, Volume and Issue: 78(13), P. 3574 - 3588

Published: April 27, 2018

Abstract Sialic acid sugars on the surface of cancer cells have emerged as potent immune modulators that contribute to immunosuppressive microenvironment and tumor evasion. However, mechanisms by which these modulate antitumor immunity well therapeutic strategies directed against them are limited. Here we report intratumoral injections with a sialic mimetic Ac53FaxNeu5Ac block expression in vivo suppress growth multiple models. blockade had major impact cell composition tumor, enhancing tumor-infiltrating natural killer CD8+ T-cell numbers while reducing regulatory myeloid numbers. enhanced cytotoxic T-cell–mediated killing part facilitating antigen-specific T-cell–tumor clustering. also synergized adoptive transfer tumor-specific T CpG adjuvant therapy increasing dendritic activation subsequent responses. Collectively, data emphasize crucial role acids evasion provide proof concept creates an immune-permissive for immunity, either single treatment or combination other immune-based intervention strategies. Significance: function important limit immunity. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3574/F1.large.jpg. Cancer Res; 78(13); 3574–88. ©2018 AACR.

Language: Английский

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Altered Cell Adhesion and Glycosylation Promote Cancer Immune Suppression and Metastasis

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Sept. 6, 2019

Cell-cell interactions and cell adhesion are key mediators of cancer progression facilitate hallmarks including immune evasion metastatic dissemination. Many molecules within the tumor microenvironment changed significant alterations glycosylation observed. These changes in alter ability cells to interact with other extracellular matrix proteins. Three families cell-cell interaction selectins, Siglecs, integrins have been associated many pre-clinical studies, yet inhibition as a therapeutic target is just beginning be explored. We review how mediated by glycan-binding receptors selectins Siglec support progression. The discussion focuses on mechanisms during metastasis that can therapeutically targeted blocking these interactions.

Language: Английский

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Carbohydrate-Based Macromolecular Biomaterials

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(18), P. 10950 - 11029

Published: Aug. 2, 2021

Carbohydrates are the most abundant and one of important biomacromolecules in Nature. Except for energy-related compounds, carbohydrates can be roughly divided into two categories: as matter information. As matter, abundantly present extracellular matrix animals cell walls various plants, bacteria, fungi, etc., serving scaffolds. Some commonly found polysaccharides featured biocompatible materials with controllable rigidity functionality, forming polymeric biomaterials which widely used drug delivery, tissue engineering, etc. information, usually referred to glycans from glycoproteins, glycolipids, proteoglycans, bind proteins or other carbohydrates, thereby meditating cell–cell cell–matrix interactions. These could simplified synthetic glycopolymers, afforded through polymerization, multistep synthesis, a semisynthetic strategy. The information role demonstrated not only targeting reagents but also immune antigens adjuvants. latter included this review they always macromolecular formulation. In review, we intend provide relatively comprehensive summary carbohydrate-based since 2010 while emphasizing fundamental understanding guide rational design biomaterials. Carbohydrate-based macromolecules on basis their resources chemical structures will discussed, including naturally occurring polysaccharides, derived glycopolymers/glycodendrimers, supramolecular glycolipids/glycoproteins. Multiscale structure–function relationships several major application areas, delivery systems, immunology, detailed. We hope valuable development build bridge between promote new biomaterial near future.

Language: Английский

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Sialylation of N-glycans: mechanism, cellular compartmentalization and function

Histochemistry and Cell Biology, Journal Year: 2016, Volume and Issue: 147(2), P. 149 - 174

Published: Dec. 14, 2016

Language: Английский

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The Chemistry of Boronic Acids in Nanomaterials for Drug Delivery

Accounts of Chemical Research, Journal Year: 2019, Volume and Issue: 52(11), P. 3108 - 3119

Published: Oct. 10, 2019

ConspectusInterest in increasing drug delivery efficiency has risen over the past decade both as a means to improve efficacy of already clinically available drugs and due increased difficulties approving new drugs. As functional group for targeted delivery, boronic acids (BAs) have been incorporated polymeric particles stimuli-responsive targeting ligand. Here, BA chemistry presents wealth opportunities biological applications. It not only reacts with several chemical markers disease such reactive oxygen species (ROS), adenosine triphosphate (ATP), glucose, reduced pH, but it also acts ligands diols sialic acid. These systems optimize therapeutics based on rational design precise molecular engineering. When designing materials containing BA, unique properties are important take into consideration its vacant p-orbital, geometry, designed acid's pKa. Instead behaving most carboxylic that donate protons, BAs instead primarily act Lewis accept electrons. In aqueous solution, polymers exist an equilibrium between their triangular hydrophobic form tetrahedral hydrophilic form. The common pKa's nonphysiological range 8–10, much ongoing research focuses modifying sensitive more physiologically relevant pH range. So far, moieties stunning array materials, ranging from small molecules can self-assemble higher order structures micelles micelles, via larger assemblies, large scale hydrogels. With abundance polyhydroxy motifs, BA-containing proven valuable biomedical applications treatment cancer, diabetes, obesity, bacterial infections. Both functionalized esters display good safety profiles vitro vivo; thus, represent promising carriers responsive great potential clinical translation.The intention this Account is showcase versatility We first discuss what consider when materials. Further, we review how recently applied nanomaterials enhanced efficiency, Lastly, current limitations further perspectives biomaterials, benefits come utilizing enhance efficiency.

Language: Английский

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Hypersialylation in Cancer: Modulation of Inflammation and Therapeutic Opportunities

Cancers, Journal Year: 2018, Volume and Issue: 10(6), P. 207 - 207

Published: June 18, 2018

Cell surface glycosylation is dynamic and often changes in response to cellular differentiation under physiological or pathophysiological conditions. Altered on cancers cells gaining attention due its wide-spread occurrence across a variety of cancer types recent studies that have documented functional roles for aberrant driving progression at various stages. One change can correlate with stage disease prognosis hypersialylation. Increased levels sialic acid are pervasive growing body evidence demonstrates how hypersialylation advantageous cells, particularly from the perspective modulating immune cell responses. Sialic acid-binding receptors, such as Siglecs Selectins, well-positioned be exploited by Evidence also mounting modulate key tumor microenvironment, those responsible maintaining appropriate inflammatory environment. From these come new innovative ways block effects directly reducing blocking interactions between Selectins. Here we review works examining become hypersialylated, benefits tumors, proposed therapies abrogate cancer.

Language: Английский

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Lectin-conjugated pH-responsive mesoporous silica nanoparticles for targeted bone cancer treatment

Acta Biomaterialia, Journal Year: 2017, Volume and Issue: 65, P. 393 - 404

Published: Nov. 8, 2017

Language: Английский

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