The presence of surfaces influences the kinetics of amyloid-β (Aβ) peptide fibrillation. Although it has been generally recognized that the fibrillation process can be assisted or accelerated by surface chemistry, the impact of surface topography, i.e., roughness, on peptide fibrillation is relatively little understood. Here we study the role of surface roughness on surface-mediated fibrillation using polymer coatings of varying roughness as well as polymer microparticles. Using single-molecule tracking, atomic force microscopy, and the thioflavin T fluorescence technique, we show that a rough surface decelerates the two-dimensional (2D) diffusion of peptides and retards the surface-mediated fibrillation. A higher degree of roughness that presents an obstacle to peptide diffusion is found to inhibit the fibrillation process.

In this report, we demonstrate the confined assembly of polymer-tethered gold nanorods in anodic aluminum oxide (AAO) channels with the assistance of electric field (EF). Various interesting hybrid assemblies, such as single-, double-, triple-, or quadruple-helix, linear, and hexagonally packed structures are obtained by adjusting pore size in AAO channels, ligand length, and EF orientation. Correspondingly, surface plasmonic property of the assemblies can thus be tuned. This strategy, by coupling of external-field and cylindrically confined assembly, is believed to be a promising approach for generating ordered hybrid assemblies with hierarchical structures, which may find potential applications in photoelectric devices, biosensors, and data storage devices.

Generally, size, uniformity, shape, and surface chemistry of biodegradable polymer particles will significantly affect the drug-release behavior in vitro and in vivo. In this study, uniform poly(d,l-lactic-co-glycolide) (PLGA) and PLGA-b-poly(ethylene glycol) (PLGA-b-PEG) microparticles with tunable surface textures were generated by combining the interfacial instabilities of emulsion droplet and polymer-blending strategy. Monodisperse emulsion droplets containing polymers were generated through the microfluidic flow-focusing technique. The removal of organic solvent from the droplets triggered the interfacial instabilities (spontaneous increase in interfacial area), leading to the formation of uniform polymer particles with textured surfaces. With the introduction of homopolymer PLGA to PLGA-b-PEG, the hydrophobicity of the polymer system was tailored, and a qualitatively different interfacial behavior of the emulsion droplets during solvent removal was observed. Uniform polymer particles with tunable surface roughness were thus generated by changing the ratio of PLGA-b-PEG in the polymer blends. More interestingly, surface textures of the particles determined the drug-loading efficiency and release kinetics of the encapsulated hydrophobic paclitaxel, which followed a diffusion-directed drug-release pattern. The polymer particles with different surface textures demonstrated good cell viability and biocompatibility, indicating the promising role of the particles in the fields of drug or gene delivery for tumor therapy, vaccines, biodiagnostics, and bioimaging.

Codelivery of combinational antigenic peptides and adjuvant to antigen presenting cells is expected to amplify tumor specific T lymphocytes immune responses while minimizing the possibility of tumor escaping and reducing immune tolerance to single antigenic peptide. However, the varied hydrophobicities of these multivariant derived short antigenic peptides limit their codelivery efficiency in conventional delivery systems. Here, a facile yet effective route is presented to generate monodisperse and stable hollow mesoporous silica nanoparticles (HMSNs) for codelivering of HGP100 and TRP2 , two melanoma-derived peptides with varied hydrophobicities. The HMSNs with large pore size can improve the encapsulation efficiency of both HGP100 and TRP2 after NH modification on the inner hollow core and COOH modification in the porous channels. HGP100 and TRP2 loaded HMSNs (HT@HMSNs) are further enveloped within monophosphoryl lipid A adjuvant entrapped lipid bilayer (HTM@HMLBs), for improved stability/biocompatibility and codelivery efficiency of multiple peptides, adjuvant, and enhanced antitumor immune responses. HTM@HMLBs increase uptake by dendritic cells (DCs) and stimulate DCs maturation efficiently, which further induce the activation of both tumor specific CD8 and CD4 T lymphocytes. Moreover, HTM@HMLBs can significantly inhibit tumor growth and lung metastasis in murine melanoma models with good safety profiles. HMSNs enveloped with lipid bilayers (HMLBs) are believed to be a promising platform for codelivery of multiple peptides, adjuvant, and enhancement of antitumor efficacy of conventional vaccinations.

Dacarbazine (DTIC) is one of the most important chemotherapeutic agents for the treatment of melanoma; however, its poor solubility, photosensitivity, instability, and serious toxicity to normal cells limit its clinical applications. In this article, we present a rationally designed nanocarrier based on hollow mesoporous silica nanoparticles (HMSNs) for the encapsulation and targeted release of DTIC for eradicating melanoma. The nanocarrier (DTIC@HMLBFs) is prepared by modifying HMSNs with carboxyl groups to enhance the loading of DTIC, followed by further enveloping of folic acid-grafted liposomes, which act as a melanoma active target for controlled and targeted drug release. In vitro, DTIC@HMLBFs exhibited the strongest cytotoxicity to melanoma cells compared with DTIC@HMSNs and free DTIC. The in vivo investigations demonstrate that the rationally designed nanocarrier loaded with DTIC achieves significant improvement against lung metastasis of melanoma via targeting melanoma cells and tumor-associated macrophages. This study provides a promising platform for the design and fabrication of multifunctional nanomedicines, which are potentially useful for the treatment of melanoma.