Thermoresponsive Polymeric Nanoparticles: Nucleation from Cooperative Polymerization Driven by Dative Bonds

Cooperative polymerization, aided by the nucleation–elongation 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 poly­(2-(diisopropylamino)­ethyl methacrylate-<i>b</i>-poly­(4-formylphenyl methacrylate-<i>co</i>-polyethylene glycol monomethyl ether methacrylate) (PDPA-<i>b</i>-P­(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 ∼ 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>, 9558–9570; <i>ACS Nano</i>, <b>2013</b>, <i>7</i>, 9518–9525). In this article, both mitomycin C (MMC) and methotrexate (MTX) loaded DSPE-PEG micelles (MTX–M–MMC) were prepared by self-assembly using the dialysis technique, in which MMC–soybean phosphatidylcholine complex (drug–phospholipid complex) was encapsulated within MTX-functionalized DSPE-PEG micelles. MTX–M–MMC 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, MTX–M–MMC 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 B–N 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