4 research outputs found
Thermoresponsive Polymeric Nanoparticles: Nucleation from Cooperative Polymerization Driven by Dative Bonds
Cooperative polymerization, aided
by the nucleationâelongation mechanism, has the promise of
providing polymers and nanostructures that are otherwise inaccessible.
The molecular origin of the cooperative growth of polymers is driven
by a secondary interaction, often based on polarization, electrostatics,
or sterics-driven secondary structure. Here, we demonstrate that covalent
dative interactions can be used to achieve cooperative polymerization.
Our results suggest that the initial polymer formation serves as the
nucleus for monodisperse nanoparticle assembly. The dynamic nature
of the dative interaction in this equilibrium self-assembly has been
shown to endow these nanoparticles with thermal responsive characteristics
A Simple Dual-pH Responsive Prodrug-Based Polymeric Micelles for Drug Delivery
To
precisely deliver drug molecules at a targeted site and in a controllable
manner, there has been great interest in designing a synergistical
drug delivery system that can achieve both surface charge-conversion
and controlled release of a drug in response to different stimuli.
Here we outline a simple method to construct an intelligent drug carrier,
which can respond to two different pH values, therefore achieving
charge conversion and chemical-bond-cleavage-induced drug release
in a stepwise fashion. This drug carrier comes from the self-assembly
of a block copolymer-DOX conjugate synthesized through a Schiff base
reaction between polyÂ(2-(diisopropylamino)Âethyl methacrylate-<i>b</i>-polyÂ(4-formylphenyl methacrylate-<i>co</i>-polyethylene
glycol monomethyl ether methacrylate) (PDPA-<i>b</i>-PÂ(FPMA-<i>co</i>-OEGMA)) and DOX. The surface charge of the BCP-DOX micelles
reversed from negative to positive when encountering a weakly acidic
environment due to the protonation of PDPA segments. <i>In vitro</i> cellular uptake measurement shows that the cellular uptake and internalization
of the BCP-DOX micelles can be significantly enhanced at pH âŒ
6.5. Moreover, this drug carrier exhibits a pH-dependent drug release
owing to the cleavage of the imine bond at pH < 5.5. With this
dual-pH responsive feature, these micelles may have the ability to
precisely deliver DOX to the cancer cells
Orthogonally Functionalized Nanoscale Micelles for Active Targeted Codelivery of Methotrexate and Mitomycin C with Synergistic Anticancer Effect
The design of nanoscale drug delivery
systems for the targeted
codelivery of multiple therapeutic drugs still remains a formidable
challenge (<i>ACS Nano</i>, <b>2013</b>, <i>7</i>, 9558â9570; <i>ACS Nano</i>, <b>2013</b>, <i>7</i>, 9518â9525). In this article, both mitomycin C
(MMC) and methotrexate (MTX) loaded DSPE-PEG micelles (MTXâMâMMC)
were prepared by self-assembly using the dialysis technique, in which
MMCâsoybean phosphatidylcholine complex (drugâphospholipid
complex) was encapsulated within MTX-functionalized DSPE-PEG micelles.
MTXâMâMMC could coordinate an early phase active targeting
effect with a late-phase synergistic anticancer effect and enable
a multiple-responsive controlled release of both drugs (MMC was released
in a pH-dependent pattern, while MTX was released in a protease-dependent
pattern). Furthermore, MTXâMâMMC could codeliver both
drugs to significantly enhance the cellular uptake, intracellular
delivery, cytotoxicity, and apoptosis in vitro and improve the tumor
accumulation and penetration and anticancer effect in vivo compared
with either both free drugs treatment or individual free drug treatment.
To our knowledge, this work provided the first example of the systemically
administrated, orthogonally functionalized, and self-assisted nanoscale
micelles for targeted combination cancer chemotherapy. The highly
convergent therapeutic strategy opened the door to more simplified,
efficient, and flexible nanoscale drug delivery systems
Cross-Linking Induced Self-Organization of Polymers into Degradable Assemblies
Covalently
stabilized polymer assemblies are normally fabricated from the self-assembly
of polymer chains followed by a cross-linking reaction. In this report,
we show that a cross-linking-induced self-assembly approach, in which
boronate cross-linking sites are formed by the condensation reaction
between boronic and catechol groups, can organize polymer networks
into uniform assemblies. Self-assembly of these boronate cross-linked
polymer networks adopts two different driving forces in water and
methanol solutions. Hydrophobic aggregation of polymer networks in
water solution affords spherical assemblies, while BâN dative
bond formed between boronate and imine functionalities in methanol
solution organizes the polymer networks into bundle-like assemblies.
We not only demonstrate the intrinsic stimuli-responsive degradability
of these cross-linked assemblies but also show that their degradation
can cause a controllable release of guest molecules. Moreover, bundle-like
assemblies with rough surface and exposed boronate functionalities
exhibit dramatically higher cell penetration capability than the spherical
assemblies with smooth surface and embedded boronate functionalities