10 research outputs found
Magnetic DNA Vector Constructed from PDMAEMA Polycation and PEGylated Brush-Type Polyanion with Cross-Linkable Shell
A novel magnetic-responsive complex composed of polycation,
DNA, and polyanion has been constructed via electrostatic interaction.
The magnetic nanoparticles (MNPs) were first coated with a polycation,
polyÂ[2-(dimethylamino)Âethyl methacrylate] end-capped with cholesterol
moiety (Chol-PDMAEMA<sub>30</sub>), and then binded with DNA through
electrostatic interaction; the complexes were further interacted with
the brush-type polyanion, namely polyÂ[polyÂ(ethylene glycol)Âmethyl
ether methacrylate]-<i>block</i>-polyÂ[methacrylic acid carrying
partial mercapto groups] (PPEGMA-<i>b</i>-PMAA<sub>SH</sub>). The resulting magnetic particle/DNA/polyion complexes could be
stabilized by oxidizing the mercapto groups to form cross-linking
shell with bridging disulfide (SâS) between PPEGMA-<i>b</i>-PMAA<sub>SH</sub> molecular chains. The interactions among
DNA, Chol-PDMAEMA coated MNPs, and PPEGMA-<i>b</i>-PMAA<sub>SH</sub> were studied by agarose gel retardation assay. The complexes
were fully characterized by means of zeta potential, transmission
electron microscopy (TEM), dynamic light scattering (DLS) measurements,
cytotoxicity assay, antinonspecific protein adsorption, and <i>in vitro</i> transfection tests. All these results indicate
that this kind of magnetic-responsive complex has potential applications
for gene vector
Folate-Conjugated Polyphosphoester with Reversible Cross-Linkage and Reduction Sensitivity for Drug Delivery
To improve the therapeutic
efficacy and circulation stability in
vivo, we synthesized a new kind of drug delivery carrier based on
folic acid conjugated polyphosphoester via the combined reactions
of Michael addition polymerization and esterification. The produced
amphiphilic polymer, abbreviated as PÂ(EAEP-AP)-LA-FA, could self-assemble
into nanoparticles (NPs) with core-shell structure in water and reversible
core cross-linked by lipoyl groups. Using the core cross-linked FA-conjugated
nanoparticles (CCL-FA NPs) to encapsulate hydrophobic anticancer drug
doxorubicin (DOX), we studied the stability of NPs, in vitro drug
release, cellular uptake, and targeting intracellular release compared
with both un-cross-linked FA-conjugated nanoparticles (UCL-FA NPs)
and core cross-linked nanoparticles without FA conjugation (CCL NPs).
The results showed that under the condition of pH 7.4, the DOX-loaded
CCL-FA NPs could maintain stable over 72 h, and only a little DOX
release (âź15%) was observed. However, under the reductive condition
(pH 7.4 containing 10 mM GSH), the disulfide-cross-linked core would
be broken up and resulted in 90% of DOX release at the same incubation
period. The study of methyl thiazolyl tetrazolium (MTT) assay indicated
that the DOX-loaded CCL-FA NPs exhibited higher cytotoxicity (IC<sub>50</sub>: 0.33 mg L<sup>â1</sup>) against HeLa cells than
the DOX-loaded CCL NPs without FA. These results indicate that the
core cross-linked FA-conjugated nanoparticles have unique stability
and targetability
One-Pot Synthesis of pH/Redox Responsive Polymeric Prodrug and Fabrication of Shell Cross-Linked Prodrug Micelles for Antitumor Drug Transportation
Shell cross-linked
(SCL) polymeric prodrug micelles have the advantages
of good blood circulation stability and high drug content. Herein,
we report on a new kind of pH/redox responsive dynamic covalent SCL
micelle, which was fabricated by self-assembly of a multifunctional
polymeric prodrug. At first, a macroinitiator PBYP-<i>ss</i>-<i>i</i>BuBr was prepared via ring-opening polymerization
(ROP), wherein PBYP represents polyÂ[2-(but-3-yn-1-yloxy)-2-oxo-1,3,2-dioxaphospholane].
Subsequently, PBYP-<i>hyd</i>-DOX-<i>ss</i>-PÂ(DMAEMA-<i>co</i>-FBEMA) prodrug was synthesized by a one-pot method with
a combination of atom transfer radical polymerization (ATRP) and a
CuÂ(I)-catalyzed azideâalkyne cycloaddition (CuAAC) reaction
using a doxorubicin (DOX) derivative containing an azide group to
react with the alkynyl group of the side chain in the PBYP block,
while DMAEMA and FBEMA are the abbriviations of <i>N</i>,<i>N</i>-(2-dimethylamino)Âethyl methacrylate and 2-(4-formylbenzoyloxy)Âethyl
methacrylate, respectively. The chemical structures of the polymer
precursors and the prodrugs have been fully characterized. The SCL
prodrug micelles were obtained by self-assembly of the prodrug and
adding cross-linker dithiol bisÂ(propanoic dihydrazide) (DTP). Compared
with the shell un-cross-linked prodrug micelles, the SCL prodrug micelles
can enhance the stability and prevent the drug from leaking in the
body during blood circulation. The average size and morphology of
the SCL prodrug micelles were measured by dynamic light scattering
(DLS) and transmission electron microscopy (TEM), respectively. The
SCL micelles can be dissociated under a moderately acidic and/or reductive
microenvironment, that is, endosomal/lysosomal pH medium or high GSH
level in the tumorous cytosol. The results of DOX release also confirmed
that the SCL prodrug micelles possessed pH/reduction responsive properties.
Cytotoxicity and cellular uptake analyses further revealed that the
SCL prodrug micelles could be rapidly internalized into tumor cells
through endocytosis and efficiently release DOX into the HeLa and
HepG2 cells, which could efficiently inhibit the cell proliferation.
This study provides a fast and precise synthesis method for preparing
multifunctional polymer prodrugs, which hold great potential for optimal
antitumor therapy
Synthesis of PEGylated Ferrocene Nanoconjugates as the Radiosensitizer of Cancer Cells
Radiation is one of the most widely
used methods for cancer diagnosis
and therapy. Herein, we report a new type of radiation sensitizer
(Fc-PEG) by a facile one-step reaction of conjugating the hydrophilic
PEG chain with hydrophobic ferrocene molecule. The chemical composition
and structure of Fc-PEG have been thoroughly characterized by FT-IR,
NMR, GPC, and MALDI-TOF mass spectrometry. This Fc-PEG conjugate could
self-assemble in aqueous solution into spherical aggregates, and it
was found that the exposure to 4 Gy of X-ray radiation have little
influence on the shape and size of these aggregates. After the chemical
bonding with PEG chains, the uptake level of Fe element could be enhanced
via the formation of aggregates. The live/dead, CCK-8, as well as
apoptosis assays, indicated that the death of cancer cells can be
obviously increased by X-ray radiation after the incubation of these
Fc-based nanoconjugates, which might be served as the radiation sensitizer
toward cancer cells. We suggest that this radiosensitizing effect
comes from the enhancement of reactive oxygen specimen (ROS) level
as denoted by both flow cytometric and fluorescence microscopic analysis.
The enhanced radiation sensitivity of cancer cells is contributed
by the synergic effect of Fe-induced radiation-sensitizing and the
increased uptake of nanoconjugates after polymeric grafting
Janus [3:5] PolystyreneâPolydimethylsiloxane Star Polymers with a Cubic Core
We
describe the precision synthesis and self-assembly of a series
of Janus star polymers with mixed [3:5] heteroarms of polystyrene
(PS) and polydimethylÂsiloxane (PDMS) precisely arranged on a
cubic scaffold of T<sub>8</sub> polyhedral oligomeric silsesquioxane
(POSS) in a spatially segregated fashion. The synthesis begins with
a Janus POSS compound with three 2-hydroxylethyl groups on one face
and five vinyl pendant groups on the rest vertexes. Facilitated by
esterification and a âclickâ adaptor, two types of polymer
arms are attached efficiently by sequential âclickâ
reactions, which constitutes a general approach for modular synthesis
of such Janus star polymers. The Janus feature is thoroughly characterized
using NMR, FT-IR, SEC, and MALDI-TOF mass spectrometry, and the self-assembled
structures are studied by small-angle X-ray scattering (SAXS) experiments.
With increasing molecular weight of PS arm, the self-assembled phase
transits from lamellae (LAM) to hexagonally packed cylinder (HEX)
and further to inversed HEX structure, even though the molecular weight
of each PDMS arm is as small as 1.4 kDa. Correspondingly, the feature
sizes of these samples are very small. For example, the intercolumnar
distance is only âź6.4 nm in the HEX phase, and the column radius
is as small as 1.8 nm. It is anticipated that diverse nanostructures
can be created from the self-assembly of these Janus star polymers
Rapid and Efficient Anionic Synthesis of Well-Defined Eight-Arm Star Polymers Using OctavinylPOSS and Poly(styryl)lithium
A new approach has been developed for the preparation
of well-defined,
eight-arm star polymers via the addition of polyÂ(styryl)lithium to
octavinylPOSS in benzene. The reaction proceeds rapidly to completion
(within 5 min for molecular weight of each arm up to 33 kg/mol), forming
predominantly eight-arm star polymers. The products were purified
by fractionation and fully characterized by <sup>1</sup>H NMR, <sup>13</sup>C NMR, <sup>29</sup>Si NMR, FT-IR, MALDI-TOF mass spectrometry,
and size exclusion chromatography. Compared to conventional coupling
approaches, this process is found to be less sensitive to the stoichiometry
of the reactants and the molecular weight of each arm. A mechanism
based on cross-association and intra-aggregate addition is invoked
to account for this unusual observation. As evidence, when a polar
solvent, tetrahydrofuran, or a strongly coordinating and disassociating
Lewis base, tetramethylethylenediamine, was used to dissociate the
living polymer chains, star polymers with lower average arm numbers
than those of the products synthesized in pure benzene were formed
at the same stoichiometry of the reactants. The method has general
implications in the understanding of the reactive nature of the living
anionic polymerization and may find practical application in the synthesis
of functional star polymers of diverse compositions and architectures
Injectable and Degradable POSSâPolyphosphateâPolysaccharide Hybrid Hydrogel Scaffold for Cartilage Regeneration
The
limited self-repair capacity of articular cartilage
has motivated
the development of stem cell therapy based on artificial scaffolds
that mimic the extracellular matrix (ECM) of cartilage tissue. In
view of the specificity of articular cartilage, desirable tissue adhesiveness
and stable mechanical properties under cyclic mechanical loads are
critical for cartilage scaffolds. Herein, we developed an injectable
and degradable organicâinorganic hybrid hydrogel as a cartilage
scaffold based on polyhedral oligomeric silsesquioxane (POSS)-cored
polyphosphate and polysaccharide. Specifically, acrylated 8-arm star-shaped
POSS-poly(ethyl ethylene phosphate) (POSS-8PEEP-AC) was synthesized
and cross-linked with thiolated hyaluronic acid (HA-SH) to form a
degradable POSS-PEEP/HA hydrogel. Incorporation of POSS in the hydrogel
increased the mechanical properties. The POSS-PEEP/HA hydrogel showed
enzymatic biodegradability and favorable biocompatibility, supporting
the growth and differentiation of human mesenchymal stem cells (hMSCs).
The chondrogenic differentiation of encapsulated hMSCs was promoted
by loading transforming growth factor-β3 (TGF-β3) in the hydrogel. In addition, the injectable POSS-PEEP/HA
hydrogel was capable of adhering to rat cartilage tissue and resisting
cyclic compression. Furthermore, in vivo results revealed that the
transplanted hMSCs encapsulated in the POSS-PEEP/HA hydrogel scaffold
significantly improved cartilage regeneration in rats, while the conjugation
of TGF-β3 achieved a better therapeutic effect. The
present work demonstrated the potential of the injectable, biodegradable,
and mechanically enhanced POSS-PEEP/HA hybrid hydrogel as a scaffold
biomaterial for cartilage regeneration
Influence of Regio-Configuration on the Phase Diagrams of Double-Chain Giant Surfactants
It has been established
that a minute difference of the primary
chemical and topological structures influences the self-assembly behaviors
of giant surfactants; however, the regio-configuration effect has
been rarely reported. Herein, we report a systematic study on the
self-assembly behaviors of a series of double-chain giant surfactant
regio-isomers, which consist of a hydrophilic polyhedral oligomeric
silsesquioxane (POSS) head and two identical hydrophobic polystyrene
(PS) tails with various molecular weights tethered in <i>para</i>-, <i>meta</i>-, and <i>ortho</i>-configurations,
respectively. Small-angle X-ray scattering and transmission electron
microscopy characterizations have been combined to investigate the
phase behaviors of each sample and construct the phase diagrams for
the three isomers with respect to the molecular weights of PS tails.
It is observed that the regio-configuration significantly impacts
the self-assembly behaviors of the giant surfactant isomers, including
order-to-disorder (ODT) and order-to-order (OOT) transitions. In each
isomer system, the order-to-disorder transition temperature (<i>T</i><sub>ODT</sub>) changes nonmonotonically with the length
of PS tails, which is generally similar to the variation of <i>T</i><sub>ODT</sub> for block copolymers but also exhibits some
peculiar features associated with the rigid conformation of headgroup.
With equal length of PS tails, <i>T</i><sub>ODT</sub> of
the three isomers is in the descending order of <i>ortho</i> > <i>meta</i> > <i>para</i>. There is
a pronounced
and systematic phase boundary shift to lower volume fraction of PS
(<i>f</i><sub>PS</sub>) and to lower temperatures from <i>para</i> to <i>meta</i> to <i>ortho</i>.
This is closely related to the compoundsâ regio-configuration
and rigid 3D conformation of the headgroup and may be understood through
the lower effective <i>f</i><sub>PS</sub> as two tails get
further apart. These findings elucidate the sophisticated effect of
the regio-configuration on self-assembly behaviors. It suggests regio-configuration
as an additional factor in tuning the self-assembly of giant surfactants
at sub-10 nm or even sub-5 nm length scales, which is of significant
technical importance
Precision Synthesis and Distinct Assembly of Double-Chain Giant Surfactant Regioisomers
The delicate influence of minute
structural difference, such as
regiochemistry, on self-assembly and phase behaviors has been commonly
observed in small molecules but rarely in synthetic polymers. Herein,
we report the precision synthesis of a series of double-chain giant
surfactant regioisomers and their distinct phase structures and phase
behaviors. These giant surfactants possess a hydroxyl-functionalized
cubic T<sub>8</sub> polyhedral oligomeric silsesquioxane head and
two polystyrene tails tethered at <i>para</i>-, <i>meta</i>-, and <i>ortho</i>-configurations and were
prepared following the sequential âclickâ method. As
revealed by temperature-dependent small-angle X-ray scattering and
bright-field transmission electron microscopy, their orderâdisorder
transition temperatures decrease in the order of <i>ortho</i>-, <i>meta</i>-, and <i>para</i>-isomers, while
orderâorder transitions were observed in the <i>meta</i>-isomer from lamellae to double gyroids and in the <i>ortho</i>-isomer from double gyroids to hexagonal cylinders upon increasing
temperature. The mechanisms are elucidated by the influence of the
tethering positions on the different free energy contributions, i.e.,
the interfacial energy, the head-to-head interaction, and the entropic
energy of the tails. The distinct assembly behaviors of the three
regioisomers are unusual in macromolecules yet resemble small molecules.
It opens an avenue to fine-tune the macromolecular assembly at the
level of molecular precision