Core-shell structure of Fe3O4@MTX-LDH/Au NPs for cancer therapy.

Nearly monodispersed magnetic Fe3O4@MTX-LDH/Au nanoparticles (NPs) containing the anticancer agent of methotrexate (MTX) were prepared via a coprecipitation-electrostatic interaction strategy. Firstly, layered double hydroxide (LDH) materials were deposited over the surface of Fe3O4 NPs by the coprecipitation method. Secondly, Au NPs were successfully conjugated onto the surface of LDH through electrostatic interaction. Herein, MTX was used both as the agent for surface modification and the anticancer drug for chemotherapy. These particles presented well-defined core-shell structure, strong magnetization and a high drug-loading capacity. Furthermore, the combined treatment of cancer cells by using Fe3O4@MTX-LDH/Au for synergistic hyperthermia ablation and chemotherapy was demonstrated to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of the platform for cancer therapy.

Induction of Au-methotrexate conjugates by sugar molecules: production, assembly mechanism, and bioassay studies.

Au-methotrexate (Au-MTX) conjugates induced by sugar molecules were produced by a simple, one-pot, hydrothermal growth method. Herein, the Au(III)-MTX complexes were used as the precursors to form Au-MTX conjugates. Addition of different types of sugar molecules with abundant hydroxyl groups resulted in the formation of Au-MTX conjugates featuring distinct characteristics that could be explained by the diverse capping mechanisms of sugar molecules. That is, the instant-capping mechanism of glucose favored the generation of peanut-like Au-MTX conjugates with high colloidal stability while the post-capping mechanism of dextran and sucrose resulted in the production of Au-MTX conjugates featuring excellent near-infrared (NIR) optical properties with a long-wavelength plasmon resonance near 630-760 nm. Moreover, in vitro bioassays showed that cancer cell viabilities upon incubation with free MTX, Au-MTX conjugates doped with glucose, dextran and sucrose for 48 h were 74.6%, 55.0%, 62.0%, and 63.1%, respectively. Glucose-doped Au-MTX conjugates exhibited a higher anticancer activity than those doped with dextran and sucrose, therefore potentially presenting a promising treatment platform for anticancer therapy. Based on the present study, this work may provide the first example of using biocompatible sugars as regulating agents to effectively guide the shape and assembly behavior of Au-MTX conjugates. Potentially, the synergistic strategy of drug molecules and sugar molecules may offer the possibility to create more gold-based nanocarriers with new shapes and beneficial features for advanced anticancer therapy.

Novel morphologies of poly(allyamine hydrochloride)-methotrexate nanoassemblies for methotrexate delivery.

Poly(allylamine hydrochloride)-methotrexate (PAH-MTX) nanoassemblies with novel morphologies (i.e. nanostrips, nanorolls, nanosheets, and nanospheres) were achieved for the first time via supramolecular self-assembly directed by the synergistic action of various non-covalent interactions between PAH and MTX molecules in aqueous solution. Herein, MTX acted in a versatile manner as both a morphology-regulating agent and a small molecular hydrophobic anticancer drug. Moreover, different morphologies presented diverse drug release profiles, which may be caused by the distinctive interactions between PAH and MTX molecules. Synergistically non-covalent interactions, including electrostatic interactions, van der Waals forces, and hydrogen bonding, favored easier matrix corrosion and more rapid drug release of non-spherical structures (i.e. nanostrips, nanorolls, and nanosheets) through the ligand exchange process. On the other hand, the highly sealed encapsulation mode for hydrophobic MTX molecules made the nanospheres exhibit slower and better controlled release. In addition, in vitro bioassay tests showed that nanostrips displayed the most obvious suppression on the viability of cancer cells among other morphologies, especially after a longer duration. The strategy of using small molecular anticancer drugs not as passively delivered cargoes but as effective molecular building blocks, opens up a new way to develop self-delivering drugs for anticancer therapy.