Facile preparation of aqueous-soluble fluorescent polyethylene glycol functionalized carbon dots from palm waste by one-pot hydrothermal carbonization for colon cancer nanotheranostics.

Carbon dots (CDs) are categorized as an emerging class of zero-dimension nanomaterials having high biocompatibility, photoluminescence, tunable surface, and hydrophilic property. CDs, therefore, are currently of interest for bio-imaging and nano-medicine applications. In this work, polyethylene glycol functionalized CDs (CD-PEG) were prepared from oil palm empty fruit bunch by a one-pot hydrothermal technique. PEG was chosen as a passivating agent for the enhancement of functionality and photoluminescence properties of CDs. To prepare the CDs-PEG, the effects of temperature, time, and concentration of PEG were investigated on the properties of CDs. The as-prepared CDs-PEG were characterized by several techniques including dynamic light scattering, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, fluorescence spectroscopy, Raman spectroscopy, Fourier-transform infrared spectroscopy and Thermogravimetric analysis. The as-prepared CDs under hydrothermal condition at 220 °C for 6 h had spherical morphology with an average diameter of 4.47 nm. Upon modification, CDs-PEG were photo-responsive with excellent photoluminescence property. The CDs-PEG was subsequently used as a drug carrier for doxorubicin [DOX] delivery to CaCo-2, colon cancer cells in vitro. DOX was successfully loaded onto CDs-PEG surface confirmed by FT-IR and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometer (MALDI-TOF/MS) patterns. The selective treatment of CDs-PEG-DOX against the colorectal cancer cells, , relative to normal human fibroblast cells was succesfully demonstrated.

A novel modified chitosan/collagen coated-gold nanoparticles for 5-fluorouracil delivery: Synthesis, characterization, in vitro drug release studies, anti-inflammatory activity and in vitro cytotoxicity assay.

We report herein the development of the novel nanohybrids of gold nanoparticles reduced/stabilized/coated with collagen (AuNPs@collagen) in the first layer and subsequently modified with biotin-quat188-chitosan (Bi-QCS) in the outer layer for 5-fluorouracil (5-FU) delivery to improve cellular uptake and promote specific cell targeting of the nanocarrier. The fabrication of the layer-by-layer technique on the surface of gold nanoparticles (AuNPs) can overcome the limitation of poor drug loading capacity of the classic AuNPs from 64.67% to 87.46%. The AuNPs@collagen coated by the Bi-QCS exhibits strong electrostatic interactions between drug anion (5-FU) and amine groups of the modified chitosan as well as hydrogen bonding. Furthermore, the Bi-QCS-AuNPs@collagen demonstrated a significantly higher anti-inflammatory activity in RAW264.7 macrophage cell line. The Bi-QCS-AuNPs@collagen enhanced the activity of 5-FU approximately 3.3-fold (HeLa) and 6.2-fold (A549), compared to the free 5-Fluorouracil. According to these results, it is very promising that Bi-QCS-AuNPs@collagen can be used as an effective drug delivery carrier in the future.

Hyaluronic acid-coated gold nanorods enhancing BMP-2 peptide delivery for chondrogenesis.

Bone morphogenic protein-2 (BMP-2) knuckle epitope peptide has been recently discovered and known to activate chondrogenesis. However, the applications of this soluble peptide remain very limited due to rapid diffusion resulting in poor cellular uptake into target cells. We herein designed nanoparticles made from hyaluronic acid functionalized gold nanorods (GNRs) to conjugate with thiolated BMP-2 knuckle epitope peptide via a two-step reaction. Hyaluronic acid was modified to have thiol functional groups to replace the cetyl trimethylammonium bromide ligands on the surface of GNRs. The thiolated peptides were subsequently reacted with hyaluronic acid on the surface on GNRs via a maleimide-hydrazide crosslinker. The conjugation was confirmed by the change of surface charge of GNRs and the plasmon shift. A colorimetric peptide assay suggested more than 69% of the thiolated peptides were conjugated with the hyaluronic acid coated gold nanorods. Moreover, in vitro cell viability showed that BMP-2 conjugated hyaluronic acid functionalized gold nanorods (B2HGR) were cytocompatible and did not cause cytotoxicity to fibroblast cells. The B2HGRs also significantly promote cellular uptake of the BMP-2 peptides in both human mesenchymal stem cells and porcine chondrocytes due to multivalent ligand binding to the BMP receptors on the cell surface resulting in receptor-mediated endocytosis. The enhanced cellular uptake was clearly observed under a confocal microscope resulting in the significant activation of type II collagen gene expression and glucosaminoglycan secretion in those cells. Furthermore, our delivery system is a proof-of-concept of using scaffolds in combination with nanodelivery platform to enhance cartilaginous repair. The peptide loading capacity and the release is not limited by the scaffolds. Therefore, our delivery platform has potential applications for cartilage regeneration in a preclinical and clinical setting in the future.