Development and Optimization of Doxorubicin Loaded Poly(lactic-co-glycolic acid) Nanobubbles for Drug Delivery Into HeLa Cells

Abstract

Microbubbles (MBs, usually 2-8 microm) as ultrasound contrast agent and drug carrier are promising for ultrasonic imaging and drug delivery. However, MBs posed some limitations due to their large diameters. In the current study, we developed a nanoscale bubbles (nanobubbles, NBs) by encapsulating the doxorubicin (DOX) into poly(lactic-co-glycolic acid) (PLGA) shells (denoted as DOX-PLGA NBs) for drug delivery into cancer cells. The size, morphology, particle stability, drug encapsulation efficiency, and drug payload were determined. The results showed that the DOX-PLGA NBs were uniform (270 +/- 3 nm) and spherical with a smooth surface, and were well dispersed and stable in water. The encapsulation efficiency and payload of DOX increased with its initial loading concentrations. The release behavior of DOX from the DOX-PLGA NBs exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release at both pH 7.4 and pH 4.4, and also presented in a pH-triggered releasing profile. The qualitative analysis of cellular internalization into HeLa cells by inverted fluorescence microscope showed that the cellular uptake of DOX-PLGA NBs was both concentration- and time-dependent. Moreover, the cell viability was also investigated using CCK-8 assay. It was found that DOX-PLGA NBs showed greater HeLa cell growth inhibition effect in vitro compared with free DOX. It was concluded that the DOX-PLGA NBs were biocompatible and appropriate for anti-cancer drug delivery, and were potentially promising as a new therapeutic system for cancer treatment.

Multifunctional Core/Shell Nanoparticles Cross-linked Polyetherimide-folic Acid as Efficient Notch-1 siRNA Carrier for Targeted Killing of Breast Cancer

“…For the ultimate use of the nanoparticles as gene carrier, it is critical that these nanoparticles after coating with silica and PEI-FA retain their low toxicity, i.e ., the gene carrier should not induce cytotoxic effects 35 36 37 . In order to evaluate the cytotoxicity of resulting nanoparticles, the viability of human breast cancer MDA-MB-231 cells was tested in the presence of Fe 3 O 4 @SiO 2 (FITC)/PEI-FA, Fe 3 O 4 @SiO 2 (FITC)/PEI-FA/scrambled shRNA, or equal volume of cell culture medium as a control.…”

Ultrasound molecular imaging with cRGD-PLGA-PFOB nanoparticles for liver fibrosis staging in a rat model

“…NP cytotoxicity in the rat hepatocyte (BRL-3A) cell line was determined using a cell counting kit-8 (CCK-8) cell viability assay (Dojindo Molecular Technologies, Kumamoto, Japan) [ 47 ]. NP suspensions were sterilized under ultraviolet light for 30 min before experiments.…”

An ultrasonic nanobubble-mediated PNP/fludarabine suicide gene system: A new approach for the treatment of hepatocellular carcinoma

“…The use of traditional gene-transfer vectors, such as viral vectors, is restricted due to immunogenicity, tumorigenicity, or amplicon infection[ 16 , 17 ]. Accordingly, the use of MB/NB ultrasound agents as drug/gene carriers has received increasing attention[ 18 , 19 ], not only because they are secure and efficient but also because they are specifically distributed to irradiated tissues or target tissues for fixed-point release by ultrasound irradiation[ 20 ] or carrying specific targeted markers[ 21 ], especially NBs with smaller diameter. In this study, 5% NBs were not cytotoxic toward HepG2 cells, and plasmid DNA combined with 5% NBs was more efficiently transfected.…”