Easy and effective method to produce functionalized particles for cellular uptake

Collette, Floraine; Delatouche, Régis; Blanquart, Christophe; Gueugnon, Fabien; Grégoire, Marc; Bertrand, Philìppe; Héroguez, Valérie

doi:10.1002/pola.26357

Cited by 21 publications

(21 citation statements)

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“…Similar results were observed in the intraperitoneal model of diffuse mesothelioma after fluorescent imaging of isolated organs at different times post-injection (Figure 4) [29]. This specific passive targeting of tumor tissues by nanovectors was unusual.…”

Section: Biological Effects In Vitro and In Vivosupporting

confidence: 83%

The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy

2019

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Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. This paper deals with the synthesis of the polymeric nanoparticle platform, which was produced by Ring-Opening Metathesis Polymerization (ROMP), able to release anti-cancer drugs in dispersion, such as histone deacetylase inhibitors, into mesothelioma tumors. The core-shell nanoparticles (NPs) have stealth properties due to their poly(ethylene oxide) shell and can be viewed as universal nano-carriers on which any alkyne-modified anti-cancer molecule can be grafted by click chemistry. A cleavage reaction of the chemical bond between NPs and drugs through the contact of NPs with a medium presenting an acidic pH, which is typically a cancer tumor environment or an acidic intracellular compartment, induces a controlled release of the bioactive molecule in its native form. In our in vivo syngeneic model of mesothelioma, a highly selective accumulation of the particles in the tumor was obtained. The release of the drugs led to an 80% reduction of tumor weight for the best compound without toxicity. Our work demonstrates that the use of theranostic nanovectors leads to an optimized delivery of epigenetic inhibitors in tumors, which improves their anti-tumor properties in vivo.

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Section: Biological Effects In Vitro and In Vivosupporting

confidence: 83%

The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy

2019

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“…26,27 Blanquart described a norbornenyl-poly(ethylene oxide) nanoparticle ligand-free generic platform, made uorescent with straightforward preparation by ROMP and easily obtained a drug delivery system with facilitated functionalization by means of subsequent click chemistry. 28,29 Binder synthesized the functionalized poly-(oxanorbornene) block copolymers via a combination of ROMP and click chemistry. 30,31 Grubbs reported the preparation of well-dened liquid crystal networks by controlled "click" crosslinking of telechelic polymers produced via ROMP.…”

Section: Introductionmentioning

confidence: 99%

A “click” approach to facile synthesis of long-chain highly branched ROMP polymers

Ding

Zhu

2014

Polym. Chem.

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The click chemistry strategy was successfully applied for the preparation of long-chain highly branched ringopening metathesis polymers (LCHBPs). The hydroxyl-functionalized monotelechelic polymers with various molecular weights were synthesized first via ring-opening metathesis polymerization of N-azidopentyl oxanorbornene imide in the presence of a symmetrical functional terminating agent, and then transformed into alkynyl-monotelechelic polymers, which acted as AB n -type macromonomers for subsequent click reaction to finally produce LCHBPs as the reaction time prolonged. All intermediates, macromonomer, and the resultant LCHBPs were characterized in detail by mass spectroscopy, elemental analysis, FTIR, GPC, and NMR measurements. The experimental results showed that polymerization has a two-step feature, that is, a fast and a slow increase of the average degree of polymerization at the initial and the subsequent stages, respectively. The final LCHBPs have high molecular weight up to M n,NMR ¼ 210 600, and relatively moderate molecular weight distributions (M w /M n ¼ 2.12-1.67).

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“…0.1% N,N-diethylalanine, Alfa Aesar), Trizma®base (99.9%, Aldrich) were used without further purification. CuBr (98%, Aldrich) was purified in acetic acid and stored under inert atmosphere (glovebox), α-norbornenyl-ω-azide-poly(ethylene oxide) macromonomer 6 bare nanoparticles 10 33 and Rhodamine B labeled nanoparticles 11 26 were prepared as previously described. ACN: acetonitrile, DCM: dichloromethane, DMF: dimethyl formamide, EA: ethyl acetate, TEA: trimethylamine, THF: tetrahydrofuran, PE: petroleum ether.…”

Section: Methodsmentioning

confidence: 99%

Histone Deacetylase Inhibitors Delivery using Nanoparticles with Intrinsic Passive Tumor Targeting Properties for Tumor Therapy

Bahhaj¹,

Denis²,

Pichavant³

et al. 2016

Theranostics

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Fast clearance, metabolism and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo model of cancers. Specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. In this work, we describe a simple and flexible polymeric nanoparticle platform highly targeting the tumor in vivo and triggering impressive tumor weight reduction when functionalized with HDACi. Our nanoparticles were produced by Ring-Opening Metathesis Polymerization of azido-polyethylene oxide-norbornene macromonomers and functionalized using click chemistry. Using an orthotopic model of peritoneal invasive cancer, a highly selective accumulation of the particles in the tumor was obtained. A combination of epigenetic drugs involving a pH-responsive histone deacetylase inhibitor (HDACi) polymer conjugated to these particles gave 80% reduction of tumor weight without toxicity whereas the free HDACi has no effect. Our work demonstrates that the use of a nanovector with theranostic properties leads to an optimized delivery of potent HDACi in tumor and then, to an improvement of their anti-tumor properties in vivo.

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Easy and effective method to produce functionalized particles for cellular uptake

Cited by 21 publications

References 50 publications

The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy

The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy

A “click” approach to facile synthesis of long-chain highly branched ROMP polymers

Histone Deacetylase Inhibitors Delivery using Nanoparticles with Intrinsic Passive Tumor Targeting Properties for Tumor Therapy

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