Preparation and pharmacokinetics of bifunctional epirubicin-loaded micelles.

In this study, micelles were designed to deliver an antitumor agent and a fluorescent marker to a tumor site. The micelles simultaneously encapsulated epirubicin (EPI) and polyethylene glycol (PEG)-modified graphene quantum dots (GQDs-PEG), and employed a PEG-polylactic acid block copolymer amphiphilic block polymer as a nanocarrier. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were used to characterize the functional groups in the synthesized GQDs-PEG. A Malvern particle size meter and transmission electron microscopy were used to show that the particle size of the GQDs-PEG is approximately 2-9 nm, and that of the bifunctional EPI-loaded micelles (EPI-FIDCR) is 19.59±1.21 nm, with zeta potential at -22.87±0.85 mV. The EE% and DL% for EPI in EPI-FIDCR are 74.02±0.55 % and 3.78±0.28 %, respectively. The IC50 values of EPI-FIDCR and EPI solution (EPI-Free) for tumor cells were 7.03 µg/mL and 5.54 µg/mL, showing that EPI-FIDCR still maintained strong cytotoxicity. Fluorescence micrographs of HeLa cells incubated with GQDs-PEG and EPI-FIDCR for 6 h, respectively, show that only EPI-FIDCR could enter the cells. In vitro cellular uptake assays and an inhibition study indicated that EPI-FIDCR could deliver both EPI and GQDs-PEG into tumor cells, while maintaining an inhibitory effect similar to that of unencapsulated EPI. A pharmacokinetic study showed that EPI-FIDCR could persist in the circulation for a significant period of time. The AUC0→t calculated for the EPI-FIDCR formulation was 159.5-fold compared with that of EPI-Free, based on its improved stability and prolonged blood circulation time. The EPI-FIDCR enables both fluorescence imaging and controlled drug-release, exhibits prolonged systematic circulation time and has potential for the treatment of cancer.

Construction of novel multifunctional luminescent nanoparticles based on DNA bridging and their inhibitory effect on tumor growth.

Cyclic RGD peptide was introduced onto the surface of silver nanoparticle (AgNP)-single strand DNA (ssDNA)-graphene quantum dots (GQDs) (ADG) after coating with a hybrid phospholipid material (ADG-DDPC) to be used for antitumor treatment. The Ag and ssDNA content was quantified. The morphology and properties of the nanoparticles were characterized by ultraviolet-visible absorption spectroscopy (UV-VIS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The etching effect of H2O2 on the AgNPs and the cleavage of DNA was observed. The cytotoxicity of the ADG-DDPC was investigated using the cell viability and LDH content. The cell uptake was evaluated by using the fluorescence recovery of the GQDs in the ADG-DDPC. The antitumor effects of ADG-DDPC were also evaluated. The content of the ssDNA was 15.3 µg mL-1. The content of the silver element in AgNPs was 3.75 µg mL-1 and 20.43 µg mL-1 in ADG-DDPC. ADG were distributed uniformly with the GQDs on the surface. After coating with hybrid phospholipid membranes containing DSPE-PEG2000-cRGD, ADG-DDPC was detected with an average size of 25.2 nm with a low IC50 of 209.68 ng mL-1 and showed LDH activity on HeLa cells. A better cellular uptake of ADG-DDPC was observed in HeLa cells, compared with cRGD-unmodified ADG nanoparticles (ADG-DDP), up to 6 and 12 h using the fluorescence recovery of GQDs as a measurement. Compared with ADG-DDP (3.6 mg of silver equivalent per kg body weight), ADG-DDPC at the same dose significantly halted 50.9% of tumor growth with little change to body weights when compared with a PTX Injection (10 mg kg-1). The novel nanoparticles, ADG-DDPC, could target tumor sites to exhibit multifunctional inhibition on tumor growth with little toxicity.