Controlling the behavior of stem cells through the supramolecular architecture of the extracellular matrix remains an important challenge in the culture of stem cells. Herein, we report on a new ...generation of low‐molecular‐weight gelators (LMWG) for the culture of isolated stem cells. The bola‐amphiphile structures derived from nucleolipids feature unique rheological and biological properties suitable for tissue engineering applications. The bola‐amphiphile‐based hydrogel scaffold exhibits the following essential properties: it is nontoxic, easy to handle, injectable, and features a biocompatible rheology. The reported glycosyl‐nucleoside bola‐amphiphiles (GNBA) are the first examples of LMWG that allow the culture of isolated stem cells in a gel matrix. The results (TEM observations and rheology) suggest that the supramolecular organizations of the matrix play a role in the behavior of stem cells in 3D environments.
Culture medium: Glycosyl‐nucleoside bola‐amphiphiles (GNBAs) are low‐molecular‐weight gelators that allow the culture of isolated stem cells in a gel matrix. The reported results highlight the role of the supramolecular organization of the matrix on the behavior of stem cells in 3D environments.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although the application of sorafenib, a small inhibitor of tyrosine protein kinases, to cancer treatments remains a worldwide option in chemotherapy, novel strategies are needed to address the low ...water solubility (< 5 μM), toxicity, and side effects issues of this drug. In this context, the use of nanocarriers is currently investigated in order to overcome these drawbacks. In this contribution, we report a new type of sorafenib-based nanoparticles stabilized by hybrid nucleoside-lipids. The solid lipid nanoparticles (SLNs) showed negative or positive zeta potential values depending on the nucleoside-lipid charge. Transmission electron microscopy of sorafenib-loaded SLNs revealed parallelepiped nanoparticles of about 200 nm. Biological studies achieved on four different cell lines, including liver and breast cancers, revealed enhanced anticancer activities of Sorafenib-based SLNs compared to the free drug. Importantly, contrast phase microscopy images recorded after incubation of cancer cells in the presence of SLNs at high concentration in sorafenib (> 80 μM) revealed a total cancer cell death in all cases. These results highlight the potential of nucleoside-lipid-based SLNs as drug delivery systems.
Heat shock protein 27 (Hsp27) has an established role in tumor progression and chemo-resistance of castration-resistant prostate cancer (CRPC). Hsp27 protects eukaryotic translation initiation factor ...4E (eIF4E) from degradation, thereby maintaining survival during treatment. Phenazine derivative compound #14 was demonstrated to specifically disrupt Hsp27/eIF4E interaction and significantly delay castration-resistant tumor progression in prostate cancer xenografts. In the present work, various strategies of encapsulation of phenazine #14 with either DOTAU (N-5'-(2',3'-dioleoyl)uridine-N',N',N'-trimethylammonium tosylate) and DOU-PEG
(5'-PEG2000-2',3'-dioleoyluridine) nucleolipids (NLs) were developed in order to improve its solubilization, biological activity, and bioavailability. We observed that NLs-encapsulated phenazine #14-driven Hsp27-eIF4E interaction disruption increased cytotoxic effects on castration-resistant prostate cancer cell line and inhibited tumor growth in castration-resistant prostate cancer cell xenografted mice compared to phenazine #14 and NLs alone. Phenazine #14 NL encapsulation might represent an interesting nanostrategy for CRPC therapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Hydrogels formed by the self‐assembly of low‐molecular‐weight gelators (LMWGs) are promising scaffolds for drug‐delivery applications. A new biocompatible hydrogel, resulting from the self‐assembly ...of nucleotide‐lipid salts can be safely injected in vivo. The resulting hydrogel provides sustained‐release of protein for more than a week.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Controlling the behavior of stem cells through the supramolecular architecture of the extracellular matrix remains an important challenge in the culture of stem cells. Herein, we report on a new ...generation of low‐molecular‐weight gelators (LMWG) for the culture of isolated stem cells. The bola‐amphiphile structures derived from nucleolipids feature unique rheological and biological properties suitable for tissue engineering applications. The bola‐amphiphile‐based hydrogel scaffold exhibits the following essential properties: it is nontoxic, easy to handle, injectable, and features a biocompatible rheology. The reported glycosyl‐nucleoside bola‐amphiphiles (GNBA) are the first examples of LMWG that allow the culture of isolated stem cells in a gel matrix. The results (TEM observations and rheology) suggest that the supramolecular organizations of the matrix play a role in the behavior of stem cells in 3D environments.
Kulturmedium: Glycosylnukleosid‐Bolaamphiphile (GNBAs) sind Gelbildner mit niedrigem Molekulargewicht, in deren Gelmatrix die Kultivierung isolierter Stammzellen möglich ist. Die erzielten Ergebnisse unterstreichen die Rolle der supramolekularen Organisation der Matrix für das Verhalten von Stammzellen in 3D‐Umgebungen.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Lipid‐based delivery systems are an established technology with considerable clinical acceptance and several applications in human. Herein, we report the design, synthesis and evaluation of novel ...orthoester nucleoside lipids (ONLs) for the modulation of liposome stability. The ONLs contain head groups with 3′‐orthoester nucleoside derivatives featuring positive or negative charges. The insertion of the orthoester function in the NL structures allows the formation of pH‐sensitive liposomes. ONL‐based liposomes can be hydrolyzed to provide nontoxic products, including nucleoside derivatives and hexadecanol. To allow the release to be tunable at different hydrolysis rates, the charge of the polar head structure is modulated, and the head group can be released at a biologically relevant pH. Crucially, when ONLs are mixed with natural phosphocholine lipids (PC), the resultant liposome evolves toward the formation of a hexadecanol/PC lamellar system. Biological evaluation shows that stable nucleic acid lipid particles (SNALPs) formulated with ONLs and siRNAs can effectively enter into tumor cells and release their nucleic acid payload in response to an intracellular acidic environment. This results in a much higher antitumor activity than conventional SNALPs. The ability to use pH‐cleavable nucleolipids to control the stability of lipid‐based delivery systems represents a promising approach for the intracellular delivery of drug cargos.
Orthoester nucleoside lipids (ONLs) reported here are the first examples of pH‐cleavable lipids that generate hexadecanol in the bilayers resulting in destabilization of vesicles under weak acidic conditions. Stable nucleic acid lipid particles (SNALPs) formulated with ONLs and siRNAs can effectively release their nucleic acid payload in response to an intracellular acidic environment. pH‐cleavable ONLs releasing fatty alcohols represent a promising approach for the intracellular delivery of drug cargos.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The back cover picture shows Orthoester Nucleoside Lipids (ONLs) allowing the formation of pH‐cleavable liposomes. These hybrid nucleolipids can be hydrolyzed at a biologically relevant pH to provide ...nontoxic nucleoside derivatives and hexadecanol. When ONLs are mixed with natural phosphocholine lipids, the liposomes evolve towards the formation of lamellar systems. Stable Nucleic Acid Lipid Particles (SNALPs) formulated with siRNAs and ONLs were able to release their nucleic acid payload in response to an intracellular acidic environment. More details can be found in the Communication by Philippe Barthélémy et al. on page 1797 in Issue 11, 2015 (DOI: 10.1002/cmdc.201500381).
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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