Graphene
oxide (GO) nanoparticles have been developed for a variety
of biomedical applications as a number of different therapeutic modalities
may be added onto them. Here, we report the development and testing
of such a multifunctional GO nanoparticle platform that contains a
grafted cell-targeting functionality, active pharmaceutical ingredients,
and particulates that enable the use of magnetothermal therapy. Specifically,
we demonstrate the ability to covalently attach hyaluronic acid (HA)
onto GO, and the resultant nanoparticulates (GO-HA) exhibited low
inherent toxicity toward two different breast cancer cell lines, BT-474
and MDA-MB-231. Doxorubicin (Dox) and paclitaxel (Ptx) were successfully
loaded onto GO-HA with high and moderate efficiencies, respectively.
A GO-HA-Dox/Ptx system was significantly better than the GO-Dox/Ptx
system at specifically killing CD44-expressing MDA-MB-231 cells but
not BT-474 cells that do not express CD44. Further, modified iron
oxide nanoparticles were loaded onto the GO-HA-Dox system, enabling
the use of magnetic hyperthermia. Hyperthermia in combination with
Dox treatment through the GO-HA system showed significantly better
performance in reducing viable tumor cell numbers when compared to
the individual systems. In summary, we showcase a multifunctional
GO nanoparticle system that demonstrates improved efficacy in killing
tumor cells.
We report the first peptide based hDHFR inhibitors designed on the basis of structural analysis of dihydrofolate reductase (DHFR). A set of peptides were rationally designed and synthesized using solid phase peptide synthesis and characterized using nuclear magnetic resonance and enzyme immunoassays. The best candidate among them, a tetrapeptide, was chosen based on molecular mechanics calculations and evaluated in human lung adenocarcinoma cell line A549. It showed a significant reduction of cell proliferation and an IC50 of 82 µM was obtained. The interaction of the peptide with DHFR was supported by isothermal calorimetric experiments revealing a dissociation constant Kd of 0.7 µM and ΔG of −34 ± 1 kJ mol−1. Conjugation with carboxylated polystyrene nanoparticles improved further its growth inhibitory effects. Taken together, this opens up new avenues to design, develop and deliver biocompatible peptide based anti-cancer agents.
In tissue engineering, the magnetic nanocomposites are more attractive due to some superior properties that promote in the monitoring of cell proliferation, differentiation and activation of cell construction in tissue regeneration phase.
Curcumin-entrapped polyaniline (PAni)-conjugated poly(3hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) electroconductive porous scaffolds were fabricated for application in tissue engineering. The physical and chemical characterizations of the as-prepared biomaterials were performed by UV−vis and ATR/FT-IR spectrophotometric, thermogravimetric, fluorescence microscopic, and X-ray diffractometric analyses. It was observed that compared to the pure PHBV copolymer, which is an insulator, the electroconductivity of the PAni-modified PHBV copolymer increased up to the value of 5.78 × 10 −5 S cm −1 . An antimicrobial study revealed that the curcumin-loaded biomaterials exhibited better bactericidal effect against Grampositive bacterial strains compared to Gram-negative strains. The composite also demonstrated significant compatibility toward blood and fibroblast cells and exhibited the maximum cell viability (90% to 80%). Cell migration and proliferation on the injured tissues were found to occur at a faster rate, resulting in faster repair, in the presence of anti-inflammatory and anticancer curcumin drug loaded composites compared to that of the pure PHBV copolymer.
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