8 research outputs found
Metal-Free Functionalization of Linear Polyurethanes by Thiol-Maleimide Coupling Reactions
Thermo-Responsive Hydrogels Encapsulating Targeted Core–Shell Nanoparticles as Injectable Drug Delivery Systems
As therapeutic agents that allow for minimally invasive administration, injectable biomaterials stand out as effective tools with tunable properties. Furthermore, hydrogels with responsive features present potential platforms for delivering therapeutics to desired sites in the body. Herein, temperature-responsive hydrogel scaffolds with embedded targeted nanoparticles were utilized to achieve controlled drug delivery via local drug administration. Poly(N-isopropylacrylamide) (pNIPAM) hydrogels, prepared with an ethylene-glycol-based cross-linker, demonstrated thermo-sensitive gelation ability upon injection into environments at body temperature. This hydrogel network was engineered to provide a slow and controlled drug release profile by being incorporated with curcumin-loaded nanoparticles bearing high encapsulation efficiency. A core (alginate)–shell (chitosan) nanoparticle design was preferred to ensure the stability of the drug molecules encapsulated in the core and to provide slower drug release. Nanoparticle-embedded hydrogels were shown to release curcumin at least four times slower compared to the free nanoparticle itself and to possess high water uptake capacity and more mechanically stable viscoelastic behavior. Moreover, this therapy has the potential to specifically address tumor tissues over-expressing folate receptors like ovaries, as the nanoparticles target the receptors by folic acid conjugation to the periphery. Together with its temperature-driven injectability, it can be concluded that this hydrogel scaffold with drug-loaded and embedded folate-targeting nanoparticles would provide effective therapy for tumor tissues accessible via minimally invasive routes and be beneficial for post-operative drug administration after tumor resection
Sequence-controlled polymerization using dendritic macromonomers: precise chain-positioning of bulky functional clusters
International audienc
Upconversion nanoparticles-based targeted imaging of MCF-7 breast cancer cells
Upconversion nanoparticles (UCNPs) doped with lanthanides are introduced as a significant tool in bioimaging applications. Here in, a comparative study has been performed to understand the cell internalization capacity of folic acid (FA) and arginine-glycine-aspartic acid-lysine (RGDK) ligands. To achieve this goal, polyacrylic acid (PAA) coated UCNPs (NaYF4:Yb3+, Er3+) are conjugated with various surface ligands such as FA and RGDK through a straightforward ligand exchange procedure. Ligand conjugation to UCNPs was characterized with a transmission electron microscope (TEM), Fourier-transform infrared (FT-IR) spectroscopy, zeta potential measurements, nuclear magnetic resonance (NMR) spectroscopy, and NanoDrop measurements. The cellular uptake of the nanoparticles was investigated on the breast cancer MCF-7 cell line. The obtained results demonstrated that folic acid and RGDK functionalized UCNPs showed remarkably higher cellular uptake, which clearly indicates that the specific targeting of UCNPs provides a better quality of sub-cellular imaging at lower energy band region
Dendrons and Multiarm Polymers with Thiol-Exchangeable Cores: A Reversible Conjugation Platform for Delivery
Disulfide
exchange reaction has emerged as a powerful tool for
reversible conjugation of proteins, peptides and thiol containing
molecules to polymeric supports. In particular, the pyridyl disulfide
group provides an efficient handle for the site-specific conjugation
of therapeutic peptides and proteins bearing cysteine moieties. In
this study, novel biodegradable dendritic platforms containing a pyridyl
disulfide unit at their focal point were designed. Presence of hydroxyl
groups at the periphery of these dendrons allows their elaboration
to multivalent initiators that yield polyÂ(ethylene glycol) based multiarm
star polymers via controlled radical polymerization. The pyridyl disulfide
unit at the core of these star polymers undergoes efficient reaction
with thiol functional group containing molecules such as a hydrophobic
dye, namely, Bodipy-SH, glutathione, and KLAK sequence containing
peptide. While conjugation of the hydrophobic fluorescent dye to the
PEG-based multiarm polymer renders it water-soluble, it can be cleaved
off the construct through thiol–disulfide exchange in the presence
of an external thiol such as dithiothreitol. The multiarm polymer
was conjugated with a thiol group containing apoptotic peptide to
increase its solubility and cellular transport. In vitro cytotoxicity
and apoptosis assays demonstrated that the resultant peptide–polymer
conjugate had almost five times more apoptotic potential primarily
through triggering apoptosis by disrupting mitochondrial membranes
of human breast cancer cell line (MDA-MB-231) compared to naked peptide.
The novel dendritic platform disclosed here offers an attractive template
that can be modified to multiarm polymeric constructs bearing a “tag
and release” characteristic
Synthesis and Functionalization of Thiol-Reactive Biodegradable Polymers
Synthesis and Functionalization
of Thiol-Reactive Biodegradable Polymer