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1.
J Colloid Interface Sci ; 581(Pt A): 185-194, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771730

RESUMO

Biomimetic nanomaterials have attracted tremendous research interest in the past decade. We recently developed biomimetic core-shell nanoparticles - silica nanocapsules, using a designer dual-functional peptide SurSi under room temperature, neutral pH and without use of any toxic reagents or chemicals. The SurSi peptide is designed capable of not only stabilizing nanoemulsions because of its excellent surface activity, but also inducing the formation of silica through biosilicification at an oil-water interface. However, it remains challenging to precisely control the peptide-induced nucleation and biosilicification specifically at the oil-water interface, thus forming oil-core silica-shell nanocapsules with uniform size and monodispersity. In this study, the fundamental mechanism of silica formation through a peptide catalyzed biosilicification was systematically investigated, so that the formation of oil-core silica-shell nanocapsules can be precisely controlled. The SurSi peptide induced hydrolysis and nucleation of biomineralized silica particles were monitored to study the biosilicification kinetics. Effects of pH, SurSi peptide concentration and pre-hydrolysis of silica precursors were also studied to optimize the formation of biomimetic silica nanocapsules. The fundamental understanding achieved through these systematic studies provides valuable insights for making core-shell nanoparticles via controlling nucleation and reaction at interfaces.

2.
Pharm Res ; 37(10): 211, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009588

RESUMO

PURPOSE: For patients with intractable cancer-related pain, administration of strong opioid analgesics and adjuvant agents by the intrathecal (i.t.) route in close proximity to the target receptors/ion channels, may restore pain relief. Hence, the aim of this study was to use bioerodable polymers to encapsulate an opioid analgesic (hydromorphone) and an adjuvant drug (ketamine) to produce prolonged-release formulations for i.t. injection. METHODS: A two-stage microfluidic method was used to fabricate nanoparticles (NPs). The physical properties were characterised using dynamic light scattering and transmission electron microscopy. A pilot in vivo study was conducted in a rat model of peripheral neuropathic pain. RESULTS: The in vitro release of encapsulated payload from NPs produced with a polymer mixture (CPP-SA/PLGA 50:50) was sustained for 28 days. In a pilot in vivo study, analgesia was maintained over a three day period following i.t. injection of hydromorphone-loaded NPs at 50 µg. Co-administration of ketamine-loaded NPs at 340 µg did not increase the duration of analgesia significantly. CONCLUSIONS: The two-stage microfluidic method allowed efficient production of analgesic/adjuvant drug-loaded NPs. Our proof-of-principle in vivo study shows prolonged hydromorphone analgesic for 78 h after single i.t. injection. At the i.t. dose administered, ketamine released from NPs was insufficient to augment hydromorphone analgesia.

3.
Small ; 16(31): e2002115, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32608187

RESUMO

Nanotheranostics have been actively sought in precision nanomedicine in recent years. However, insufficient tumor accumulation and limited cell uptake often impede the nanotheranostic efficacy. Herein, pH-sensitive charge-reversible polymer-coated layered double hydroxide (LDH) nanohybrids are devised to possess long circulation in blood but reserve surface charges in the weakly acidic tumor tissue to re-expose therapeutic LDH nanoparticles for enhanced tumor accumulation and cell uptake. In vitro experimental data demonstrate that charge-reversible nanohybrids mitigate the cell uptake in physiological conditions (pH 7.4), but remarkably facilitate internalization by tumor cells after charge reversion in the weakly acidic environment (pH 6.8). More significantly, about 6.0% of injected charge-reversible nanohybrids accumulate in the tumor tissue at 24 h post injection, far higher than the average accumulation (0.7%) reported elsewhere for nanoparticles. This high tumor accumulation clearly shows the tumor tissues in T1 -weighted magnetic resonance imaging. As a consequence, >95% inhibition of tumor growth in the B16F0-bearing mouse model is achieved via only one treatment combining RNAi and photothermal therapy under very mild irradiation (808 nm laser, 0.3 W cm-2 for 180 s). The current research thus demonstrates a new strategy to functionalize nanoparticles and simultaneously enhance their tumor accumulation and cell internalization for effective cancer theranostics.

4.
ACS Nano ; 14(6): 7425-7434, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32401485

RESUMO

Incorporation of fluorinated moieties in polymeric nanoparticles has been shown in many instances to increase their uptake by living cells and, hence, has proven to be a useful approach to enhancing delivery to cells. However, it remains unclear how incorporation of fluorine affects critical transport processes, such as interactions with membranes, intracellular transport, and tumor penetration. In this study, we investigate the influence of fluorine on transport properties using a series of rationally designed poly(oligo(ethylene glycol) methyl ether acrylate)-block-perfluoropolyether (poly(OEGA)m-PFPE) copolymers. Copolymers with different fluorine contents were prepared and exhibit aggregate in solution in a manner dependent on the fluorine content. Doxorubicin-conjugated poly(OEGA)20-PFPE nanoparticles with lower fluorine content exist in solution as unimers, leading to greater exposure of hydrophobic PFPE segments to the cell surface. This, in turn, results in greater cellular uptake, deeper tumor penetration, as well as enhanced therapeutic efficacy compared to that with the micelle-state nanoaggregates (poly(OEGA)10-PFPE and poly(OEGA)5-PFPE) with higher fluorine content but with less PFPE exposed to the cell membranes. Our results demonstrate that the aggregation behavior of these fluorinated polymers plays a critical role in internalization and transport in living cells and 3D spheroids, providing important design criteria for the preparation of highly effective delivery agents.

5.
Angew Chem Int Ed Engl ; 59(12): 4729-4735, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-31951063

RESUMO

The conjugation of hydrophilic low-fouling polymers to therapeutic molecules and particles is an effective approach to improving their aqueous stability, solubility, and pharmacokinetics. Recent concerns over the immunogenicity of poly(ethylene glycol) has highlighted the importance of identifying alternative low fouling polymers. Now, a new class of synthetic water-soluble homo-fluoropolymers are reported with a sulfoxide side-chain structure. The incorporation of fluorine enables direct imaging of the homopolymer by 19 F MRI, negating the need for additional synthetic steps to attach an imaging moiety. These self-reporting fluoropolymers show outstanding imaging sensitivity and remarkable hydrophilicity, and as such are a new class of low-fouling polymer for bioconjugation and in vivo tracking.

6.
Small ; 15(36): e1902309, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31328398

RESUMO

19 F magnetic resonance imaging (19 F MRI) agents capable of being activated upon interactions with cancer triggers are attracting increasing attention, although challenges still remain for precise and specific detection of cancer tissues. In this study, a novel hybrid 19 F MRI agent for pH-sensitive detection of breast cancer tissues is reported, a composite system designed by conjugating a perfluoropolyether onto the surface of manganese-incorporated layered double hydroxide (Mn-LDH@PFPE) nanoparticles. The 19 F NMR/MRI signals from aqueous solutions of Mn-LDH@PFPE nanoparticles are quenched at pH 7.4, but "turned on" following a reduction in pH to below 6.5. This is due to partial dissolution of Mn2+ from the Mn-LDH nanoparticles and subsequent reduction in the effect of paramagnetic relaxation. Significantly, in vivo experiments reveal that an intense 19 F MR signal can be detected only in the breast tumor tissue after intravenous injection of Mn-LDH@PFPE nanoparticles due to such a specific activation. Thus pH-activated Mn-LDH@PFPE nanoparticles are a potential "smart" 19 F MRI agent for precise and specific detection of cancer diseases.

7.
Biomacromolecules ; 20(5): 2043-2050, 2019 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-30995836

RESUMO

Imaging agents that can be targeted to specific diseases and respond to the microenvironment of the diseased tissue are of considerable interest due to their potential in diagnosing and managing diseases. Here we report a new class of branched fluorinated glycopolymers as 19F MRI contrast agents that respond to a reductive environment, for targeted imaging of cancer. The fluorinated glycopolymers can be readily prepared by a one-pot RAFT polymerization of glucose- and fluorine-containing monomers in the presence of a disulfide-containing cross-linking monomer. The incorporation of glucose units along the polymer chain enables these fluorinated glycopolymers to effectively target cancer cells due to interactions with the overexpressed sugar transporters present on the cell surface. In addition, the polymers exhibit an enhanced 19F MRI signal in response to a reductive environment, one of the unique hallmarks of many cancer cells, demonstrating their potential as promising candidates for targeted imaging of cancer.

8.
Biomacromolecules ; 20(1): 365-374, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30495941

RESUMO

An understanding of thermally induced aggregation and consequent 19F magnetic resonance imaging (MRI) performance is essential for improved design of thermoresponsive 19F MRI contrast agents. Herein we describe a series of novel thermoresponsive perfluoropolyether (PFPE)-based comb-shaped poly(2-oxazoline)s (POxs) with different side-chain structures (2-methyl- (MeOx), 2-ethyl- (EtOx), and 2-( n-propyl)-2-oxazoline (nPrOx)). The comb polymers were prepared through reversible addition-fragmentation chain transfer (RAFT) polymerization of the respective oligo(2-oxazoline)acrylates using a perfluoropolyether macro-RAFT agent. The fluoropolyether chain end drives aggregation of the polymers, with small aggregates forming at 300 K for both poly(OMeOx5A)9-PFPE and poly(OEtOx4A)9-PFPE. The aggregates decrease in size and display increases in 19F MRI intensity with temperature, and at 350 K the MeOx polymers are in the form of unimers in solution, similar to the oligoethylene glycol (OEG)-based PFPE polymer. Above the TCP of poly(OEtOx4A)9-PFPE, the polymer forms large aggregates, and the 19F MR imaging performance is degraded. Likewise, poly(OnPrOx4A)-PFPE is above the LCST at all temperatures studied (300-350 K), and so weak imaging intensity is obtained. This report of novel thermoresponsive POx-based PFPE polymers highlights the importance of understanding self-association of polymers in solution and provides important insights for the development of "smart" thermoresponsive 19F MRI contrast agents.


Assuntos
Éteres/química , Fluorcarbonetos/química , Oxazóis/química , Polímeros Responsivos a Estímulos/síntese química , Flúor/química , Imagem por Ressonância Magnética/métodos , Polimerização , Temperatura
9.
Biomacromolecules ; 19(11): 4423-4429, 2018 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-30350948

RESUMO

Iron oxide nanoparticles have been widely applied in biomedical applications for their unique physical properties. Despite the relatively mature synthetic approaches for iron oxide nanoparticles, surface modification strategies for obtaining particles with satisfactory biofunctionality are still urgently needed to meet the challenge of nanomedicine. Herein, we report a surface modification and biofunctionalization strategy for iron oxide-based magnetic nanoparticles based on a dibromomaleimide (DBM)-terminated polymer with brushed polyethylene glycol (PEG) chains. PEG acrylate and phosphonate monomers, serving as antibiofouling and surface anchoring compartments for iron oxide nanoparticles, were incorporated utilizing a novel DBM containing reversible addition-fragmentation chain transfer (RAFT) agent. The particles prepared through this new surface architecture possessed high colloidal stability in a physiological buffer and the capacity of covalent conjugation with biomolecules for targeting. Cell tracking of the molecular probes was achieved concomitantly by exploiting DBM conjugation-induced fluorescence of the nanoparticles.


Assuntos
Rastreamento de Células/métodos , Compostos Férricos/química , Fluorescência , Maleimidas/química , Nanopartículas/química , Polietilenoglicóis/química , Polímeros/química , Bromo/química , Sobrevivência Celular , Células HEK293 , Humanos , Células MCF-7 , Nanomedicina
10.
Angew Chem Int Ed Engl ; 56(29): 8376-8383, 2017 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-27925363

RESUMO

Uniform synthetic polymers with precisely defined molar mass and monomer sequence (primary structure) have many potential high-value applications. However, a robust and versatile synthetic strategy for these materials remains one of the great challenges in polymer synthesis. Herein we describe proof-of-principle experiments for a modular strategy to produce discrete oligomers by a visible-light-mediated radical chain process. We utilize the high selectivity provided by photo-induced electron/energy transfer (PET) activation to develop efficient single unit monomer insertion (SUMI) into reversible addition-fragmentation chain-transfer (RAFT) agents. A variety of discrete oligomers (single unit species, dimers, and, for the first time, trimers) have been synthesized by sequential SUMI in very high yield under mild reaction conditions. The trimers were used as building blocks for the construction of uniform hexamers and graft copolymers with precisely defined branches.

11.
Chem Commun (Camb) ; 52(44): 7126-9, 2016 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-27167862

RESUMO

A novel methodology of visible light regulated ring opening polymerization in the presence of reversible merocyanine-based photoacid was reported for the first time. In combination with a photoinduced radical polymerization technique, a dual wavelength light controlled orthogonal polymerization system was investigated to switch the polymerization between two different monomers and for the preparation of block and graft copolymers in one pot.

12.
J Am Chem Soc ; 138(9): 3094-106, 2016 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-26914442

RESUMO

Here, we exploit the selectivity of photoactivation of thiocarbonylthio compounds to implement two distinct organic and polymer synthetic methodologies: (1) a single unit monomer insertion (SUMI) reaction and (2) selective, controlled radical polymerization via a visible-light-mediated photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) process. In the first method, precise single unit monomer insertion into a dithiobenzoate with a high reaction yield (>97%) is reported using an organic photoredox catalyst, pheophorbide a (PheoA), under red light irradiation (λmax = 635 nm, 0.4 mW/cm(2)). The exceptional selectivity of PheoA toward dithiobenzoate was utilized in combination with another catalyst, zinc tetraphenylporphine (ZnTPP), for the preparation of a complex macromolecular architecture. PheoA was first employed to selectively activate a dithiobenzoate, 4-cyanopentanoic acid dithiobenzoate, for the polymerization of a methacrylate backbone under red light irradiation. Subsequently, metalloporphyrin ZnTPP was utilized to selectively activate pendant trithiocarbonate moieties for the polymerization of acrylates under green light (λmax = 530 nm, 0.6 mW/cm(2)) to yield well-defined graft co-polymers.

13.
ACS Appl Mater Interfaces ; 6(3): 2026-30, 2014 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-24397710

RESUMO

Thermo and pH dual-controllable oil/water separation materials are successfully fabricated by photo initiated free radical polymerization of dimethylamino ethyl methacrylate (DMAEMA). The PDMAEMA hydrogel coated mesh shows superhydrophilicity and underwater superoleophobicity at certain temperature and pH. Due to the double responsiveness of PDMAEMA hydrogel, the as-prepared mesh can selectively separate water from oil/water mixtures and make water and oil permeate through the mesh orderly and be collected separately by adjusting the temperature or pH. Water can pass through the as-prepared mesh under 55 °C (pH 7) and pH less than 13 (T = 25 °C) while oil is kept on the mesh. When the temperature is above 55 °C or pH is larger than 13, the water retention capacity of PDMAEMA hydrogel is significantly reduced and the swelling volume is decreased. Therefore, oil can permeate through the mesh and be collected in situ. Additionally, this material has excellent potential to be used in practical applications and has created a new field for water/oil separation in which the process can be diversified and more intelligent.

14.
J Biomater Sci Polym Ed ; 24(13): 1564-74, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23560850

RESUMO

A straightforward method to prepare nonionic polymer (polyacrylamide, PAM) cross-linked chitosan hydrogel has been developed. The chitosan-polyacrylamide (CS-PAM) hydrogel could be quickly obtained by simply mixing of chitosan and polyacrylamide solutions under very benign condition (room temperature, <30 s). The cytotoxicity and hemocompatibility of the CS-PAM hydrogel were subsequently investigated. Cells retained normal morphology even when the concentration of CS-PAM hydrogel in culture system was as high as 640 µg mL(-1), indicating the CS-PAM hydrogel has minimal cytotoxicity to A549 and HeLa cells. Meanwhile, no hemolysis was observed after incubating the CS-PAM hydrogel with red blood cells for 6 h, further suggesting excellent biocompatibility of the hydrogel. Scanning electron microscopy images illustrated that the CS-PAM hydrogel can absorb red blood cells through the interaction between the protonated amine groups on chitosan and the negative charged residues on red blood cell membranes. Given its low cost, simple preparation, and excellent biocompatibility, this CS-PAM hydrogel might be a potential biomaterial for future healthcare and biomedical applications.


Assuntos
Resinas Acrílicas/química , Materiais Biocompatíveis/química , Quitosana/química , Resinas Acrílicas/isolamento & purificação , Resinas Acrílicas/toxicidade , Adsorção , Animais , Materiais Biocompatíveis/isolamento & purificação , Materiais Biocompatíveis/toxicidade , Linhagem Celular , Quitosana/isolamento & purificação , Quitosana/toxicidade , Reagentes para Ligações Cruzadas , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Masculino , Teste de Materiais , Ratos , Ratos Wistar , Reologia
16.
Chem Commun (Camb) ; 48(72): 9062-4, 2012 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-22864118

RESUMO

A facile "one-pot" chemoenzymatic-ATRP has been successfully developed through the combination of copper-catalytic ATRP and enzyme-catalytic monomer transformation reactions.


Assuntos
Polimerização , Polímeros/química , Biocatálise , Cobre/química , Proteínas Fúngicas/metabolismo , Lipase/metabolismo , Peso Molecular
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