Cyclodextrin-based supramolecular systems for drug delivery: recent progress and future perspective.
TL;DR: This review focuses on state of the art and recent advances in the construction of cyclodextrin-based assemblies and their applications for controlled drug delivery and the future directions of this field are discussed.
About: This article is published in Advanced Drug Delivery Reviews.The article was published on 2013-08-01 and is currently open access. It has received 673 citations till now.
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TL;DR: This review focuses on various potential applications of supramolecular hydrogels as molecular biomaterials, classified by their applications in cell cultures, tissue engineering, cell behavior, imaging, and unique applications of hydrogelators.
Abstract: In this review we intend to provide a relatively comprehensive summary of the work of supramolecular hydrogelators after 2004 and to put emphasis particularly on the applications of supramolecular hydrogels/hydrogelators as molecular biomaterials. After a brief introduction of methods for generating supramolecular hydrogels, we discuss supramolecular hydrogelators on the basis of their categories, such as small organic molecules, coordination complexes, peptides, nucleobases, and saccharides. Following molecular design, we focus on various potential applications of supramolecular hydrogels as molecular biomaterials, classified by their applications in cell cultures, tissue engineering, cell behavior, imaging, and unique applications of hydrogelators. Particularly, we discuss the applications of supramolecular hydrogelators after they form supramolecular assemblies but prior to reaching the critical gelation concentration because this subject is less explored but may hold equally great promise for helping ...
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TL;DR: Host−Guest Supramolecular Chemistry A 1.1.1: Aims to explore the role of “ghostly” particles in the determination of chiral stationary phases and their role in the “spatially modified” states.
Abstract: 1. Host−Guest Supramolecular Chemistry A 1.
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TL;DR: A historical overview of the developments in hydrogel research from simple networks to smart materials is provided to overcome several challenges to overcome for clinical translation.
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TL;DR: The ability of rationally engineered drug–nanoparticle combinations to efficiently modulate tumour-associated macrophages for cancer immunotherapy is demonstrated and R848, an agonist of the toll-like receptors TLR7 and TLR8 identified in a morphometric-based screen, is a potent driver of the M1 phenotype in vitro.
Abstract: Tumour-associated macrophages are abundant in many cancers, and often display an immune-suppressive M2-like phenotype that fosters tumour growth and promotes resistance to therapy. Yet, macrophages are highly plastic and can also acquire an anti-tumorigenic M1-like phenotype. Here, we show that R848, an agonist of the toll-like receptors TLR7 and TLR8 identified in a morphometric-based screen, is a potent driver of the M1 phenotype in vitro and that R848-loaded β-cyclodextrin nanoparticles (CDNP-R848) lead to efficient drug delivery to tumour-associated macrophages in vivo. As a monotherapy, the administration of CDNP-R848 in multiple tumour models in mice altered the functional orientation of the tumour immune microenvironment towards an M1 phenotype, leading to controlled tumour growth and protecting the animals against tumour rechallenge. When used in combination with the immune checkpoint inhibitor anti-PD-1, we observed improved immunotherapy response rates, including in a tumour model resistant to anti-PD-1 therapy alone. Our findings demonstrate the ability of rationally engineered drug-nanoparticle combinations to efficiently modulate tumour-associated macrophages for cancer immunotherapy.
601 citations
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TL;DR: How PEGylation can result in drugs that are often more effective and safer, and which show improved patient convenience and compliance are reviewed.
Abstract: Protein and peptide drugs hold great promise as therapeutic agents. However, many are degraded by proteolytic enzymes, can be rapidly cleared by the kidneys, generate neutralizing antibodies and have a short circulating half-life. Pegylation, the process by which polyethylene glycol chains are attached to protein and peptide drugs, can overcome these and other shortcomings. By increasing the molecular mass of proteins and peptides and shielding them from proteolytic enzymes, pegylation improves pharmacokinetics. This article will review how PEGylation can result in drugs that are often more effective and safer, and which show improved patient convenience and compliance.
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TL;DR: Evidence is provided of inducing an RNAi mechanism of action in a human from the delivered siRNA and the presence of an mRNA fragment that demonstrates that siRNA-mediated mRNA cleavage occurs specifically at the site predicted for anRNAi mechanism from a patient who received the highest dose of the nanoparticles.
Abstract: Therapeutics that are designed to engage RNA interference (RNAi) pathways have the potential to provide new, major ways of imparting therapy to patients. Long, double-stranded RNAs were first shown to mediate RNAi in Caenorhabditis elegans, and the potential use of RNAi for human therapy has been demonstrated by the finding that small interfering RNAs (siRNAs; approximately 21-base-pair double-stranded RNA) can elicit RNAi in mammalian cells without producing an interferon response. We are at present conducting the first in-human phase I clinical trial involving the systemic administration of siRNA to patients with solid cancers using a targeted, nanoparticle delivery system. Here we provide evidence of inducing an RNAi mechanism of action in a human from the delivered siRNA. Tumour biopsies from melanoma patients obtained after treatment show the presence of intracellularly localized nanoparticles in amounts that correlate with dose levels of the nanoparticles administered (this is, to our knowledge, a first for systemically delivered nanoparticles of any kind). Furthermore, a reduction was found in both the specific messenger RNA (M2 subunit of ribonucleotide reductase (RRM2)) and the protein (RRM2) levels when compared to pre-dosing tissue. Most notably, we detect the presence of an mRNA fragment that demonstrates that siRNA-mediated mRNA cleavage occurs specifically at the site predicted for an RNAi mechanism from a patient who received the highest dose of the nanoparticles. Together, these data demonstrate that siRNA administered systemically to a human can produce a specific gene inhibition (reduction in mRNA and protein) by an RNAi mechanism of action.
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TL;DR: The Exocytic Pathway and the CharacTERISTICS of PROTON ATPases are reviewed.
Abstract: AND PERSPECTIVES 664 THE ORGANEL L ES OF THE EXOAND ENDOCYTIC PATHWAyS . . . . . . . . . . . . . ..... 665 The Endocytic Pathway . . . . . . . . . . . . . . . . . . . . . . . . .. . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 665 The Exocytic Pathways. . . . . . . . . . . . . . . .. . . . .. . . . . . . . ...... . . . . . . . . . . . . . .. . . . . . . . . ... . . . .. . . ... . ... 667 CHARACTERISTICS OF PROTON ATPases 667
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