Fabrication of Stable and Well-Dispersed Polyaniline–Polypyrrolidone Nanocomposite for Effective Photothermal Therapy

Well-dispersed polyaniline (PANi) nanoparticles were successfully synthesized by simple oxidative polymerization of aniline in a two-phase system in the presence of poly­(vinylpyrrolidone) (PVP) as a polymer shell agent, and citric acid was used as a doping acid instead of inorganic acids due to its better biocompatibility. TEM showed that the nanocomposites of PANi and PVP (PANi@PVP) assembled into core–shell like nanostructures uniformly. MTT results indicated that the PANi@PVP nanoparticles supported the survival of cells; IC50 could reach about 2.5 mg/mL, much higher than the IC50 value reported for PANi nanoparticles without PVP. Furthermore, in the presence of PVP, only exceeding PANi (>1.5 mg/mL) resulted in a comparable production of intracellular reactive oxygen species (ROS), the induction of apoptosis in PC-12 cells, and a weaker DNA fragmentation. TEM of PC-12 cell sections displayed that the cell morphological changes associated with the apoptosis were induced when exposed to a very high dose of PANi@PVP (3 mg/mL). The well-dispersed PANi@PVP combined with NIR irradiation achieved excellent photothermal conversion performance, which could kill cancer cell BEL-7402 in vitro effectively. Reflecting this well-dispersed property, the tumors in cancer bearing KM mice disappeared thoroughly after a single subcutaneous injection of PANi@PVP nanoparticles and subsequent NIR laser irradiation

Formation of a Mimetic Biomembrane from the Hydrophobic Protein Zein and Phospholipids: Structure and Application

α-Zein, a storage protein in corn endosperm, could be purified easily and in large amounts. In this study, α-zein was incorporated into phospholipid–cholesterol (PC–Chol) liposomes. The maximal amount of α-zein incorporated in the liposome was 0.05% (mol/mol) and the PC:Zein molar ratio was near 2400. At this level of zein insertion, the phase transition temperature of the lipid bilayer was little affected, but the leakage of doxorubicin (DOX) from the PC–Chol liposome became obviously slower when α-zein was added at a higher temperature than the phase transition temperature. Cryogenic transmission electron micrographs of the PC–Chol–Zein liposome showed that adjacent membranes in multilamellar vesicles were often aligned at a regular interval of about 7 nm. Data from synchrotron small-angle X-ray scattering of the PC–Chol–Zein liposome indicated the formation of the multilamellar structure with an intermembrane interval of 7.2 nm, whereas no homogeneous membrane alignment was observed in the absence of zein. The present observation can be well explained by supposing that α-zein takes on such an elongated conformation that it penetrates through two adjacent membrane layers. This feature seems to be compatible with a recently proposed superhelical structural model of α-zein. Meanwhile, experiments with the fluorescent-labeled α-zein showed that the PC–Chol–Zein liposome could be uptaken by an intact cell and localized in some specialized area (possibly endosomes) within the cell instead of being diffusely distributed in the cell. Thus, the PC–Chol–Zein liposome seems to act as an interesting biomembrane model and may be applicable as a drug delivery system

3D Printed Alginate Hydrogels with Stiffness-Gradient Structure in a Carbomer Supporting Bath by Controlled Ca²⁺ Diffusion

Manufacturing biocompatible materials with higher-order structure has great significance because they can mimic the extracellular medium of the human organism and are a novel strategy for tissue regeneration. In this study, a device with stiffness-gradient characteristics based on two biocompatible materials, alginate with presolidification and photocurable acrylamide-containing supporting bath, was designed and constructed by the 3D printing technique. The presolidification can avoid rapid diffusion of alginate in aqueous solutions, improve mechanical properties without the introduction of heterogeneous gel precursor, and endow gradient stiffness by the controlled diffusion of calcium ions. Besides, a photocurable supporting bath was combined to manufacture a device with a dual-gradient structure by a 4-step procedure, including 3D printing, removal of the inner hydrogel, solidification of alginate, and curing of the supporting bath. A cylinder-like container was manufactured as the template, and the wall of the resultant container with two types of gradient structures showed parabola-like stiffness changes (open upward), resulting from calcium ion diffusion-controlled gradient solidification and alginate diffusion-controlled gradient photocuring. Moreover, the resultant device exhibited lower cytotoxicity to both adherent and suspension cells than containers manufactured with alginate. Because of the high water uptake of the photocured supporting bath, the removal of toxic metabolic products together with cell culture medium from the container leads to better cell compatibility. This diffusion-controlled device is also applicable to other additive manufacturers with biomedical significance