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A Strategy for Prompt Phase Transfer of Upconverting Nanoparticles Through Surface Oleate-Mediated Supramolecular Assembly of Amino-?-Cyclodextrin.

ABSTRACT: Lanthanide-doped upconverting nanoparticles (UCNPs) are promising for applications as wide as biosensing, bioimaging, controlled drug release, and cancer therapy. These applications require surface engineering of as-prepared nanocrystals, commonly coated with hydrophobic ligand of oleic acid, to enable an aqueous dispersion. However, literature-reported approaches often require a long time and/or multiple step treatment, along with several fold upconversion luminescence (UCL) intensity decrease. Here, we describe a strategy allowing oleate-capped UCNPs to become water-soluble and open-modified, with almost undiminished UCL, through ultrasonication of minutes. The prompt phase transfer was enabled by oleate-mediated supramolecular self-assembly of amino modified ?-cyclodextrin (amino-?-CD) onto UCNPs surface. We showed that this method is valid for a wide range of UCNPs with quite different sizes (6-400 nm), various dopant types (Er, Tm, and Ho), and hierarchical structures (core, core-shell). Importantly, the amino group of amino-?-CD on the surface of treated UCNPs provide possibilities to introduce entities for biotargeting or functionalization, as exemplified here, a carboxylic-containing near infrared dye (Cy 7.5) that sensitizes UCNPs to enhance their UCL by ~4,820 fold when excited at ~808 nm. The described method has implications for all types of oleate-capped inorganic nanocrystals, facilitating their myriad bioapplications.

SUBMITTER: Wang X

PROVIDER: S-EPMC6445860 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A Strategy for Prompt Phase Transfer of Upconverting Nanoparticles Through Surface Oleate-Mediated Supramolecular Assembly of Amino-β-Cyclodextrin.

Wang Xindong X Chen Guanying G

Frontiers in chemistry 20190327

Lanthanide-doped upconverting nanoparticles (UCNPs) are promising for applications as wide as biosensing, bioimaging, controlled drug release, and cancer therapy. These applications require surface engineering of as-prepared nanocrystals, commonly coated with hydrophobic ligand of oleic acid, to enable an aqueous dispersion. However, literature-reported approaches often require a long time and/or multiple step treatment, along with several fold upconversion luminescence (UCL) intensity decrease. ...[more]

PMID: 30972327

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Project description:Therapeutic development of histone deacetylase inhibitors (HDACi) has been hampered by a number of barriers to drug delivery, including poor solubility and inadequate tissue penetration. Nanoparticle encapsulation could be one approach to improve the delivery of HDACi to target tissues; however, effective and generalizable loading of HDACi within nanoparticle systems remains a long-term challenge. We hypothesized that the common terminally ionizable moiety on many HDACi molecules could be capitalized upon for loading in polymeric nanoparticles. Here, we describe the simple, efficient formulation of a novel library of β-cyclodextrin-poly (β-amino ester) networks (CDN) to achieve this goal. We observed that network architecture was a critical determinant of CDN encapsulation of candidate molecules, with a more hydrophobic core enabling effective self-assembly and a PEGylated surface enabling high loading (up to ∼30% w/w), effective self-assembly of the nanoparticle, and slow release of drug into aqueous media (up to 24 days) for the model HDACi panobinostat. We next constructed a library of CDNs to encapsulate various small, hydrophobic, terminally ionizable molecules (panobinostat, quisinostat, dacinostat, givinostat, bortezomib, camptothecin, nile red, and cytarabine), which yielded important insights into the structural requirements for effective drug loading and CDN self-assembly. Optimized CDN nanoparticles were taken up by GL261 cells in culture and a released panobinostat was confirmed to be bioactive. Panobinostat-loaded CDNs were next administered by convection-enhanced delivery (CED) to mice bearing intracranial GL261 tumors. These studies confirm that CDN encapsulation enables a higher deliverable dose of drug to effectively slow tumor growth. Matrix-assisted laser desorption/ionization (MALDI) analysis on tissue sections confirms higher exposure of tumor to drug, which likely accounts for the therapeutic effects. Taken in sum, these studies present a novel nanocarrier platform for encapsulation of HDACi via both ionic and hydrophobic interactions, which is an important step toward better treatment of disease via HDACi therapy.

Dataset Information

A Strategy for Prompt Phase Transfer of Upconverting Nanoparticles Through Surface Oleate-Mediated Supramolecular Assembly of Amino-?-Cyclodextrin.

Publications

A Strategy for Prompt Phase Transfer of Upconverting Nanoparticles Through Surface Oleate-Mediated Supramolecular Assembly of Amino-β-Cyclodextrin.

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