Paclitaxel-loaded poly(D,L-lactide-co-glycolide) nanoparticles for radiotherapy in hypoxic human tumor cells in vitro

Abstract

Radioresistant hypoxic cells may contribute to the failure of radiation therapy in controlling certain tumors. Some studies have suggested the radiosensitizing effect of paclitaxel. The poly (D,L-lactide-co-glycolide)(PLGA) nanoparticles containing paclitaxel were prepared by o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e., encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The morphology of the two human tumor cell lines: a carcinoma cervicis (HeLa) and a hepatoma (HepG 2 ), treated with paclitaxel-loaded nanoparticles was photomicrographed. Flow cytometry was used to quantify the number of the tumor cells held in the G 2 /M phase of the cell cycle. The cellular uptake of nanoparticles was evaluated by transmission electronic microscopy. Cell viability was determined by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 200 nm and 800 nm. The encapsulation efficiency was 85.5%. The release behaviour of paclitaxel from the nanoparticles exhibited a biphasic pattern characterised by a fast initial release during the first 24 h, followed by a slower and continuous release. Co-culture of the two tumor cell lines with paclitaxel-loaded nanoparticles demonstrated that the cell morphology was changed and the released paclitaxel retained its bioactivity to block cells in the G 2 /M phase. The cellular uptake of nanoparticles was observed. The free paclitaxel and paclitaxel-loaded nanoparticles effectively sensitized hypoxic HeLa and HepG 2 cells to radiation. Under this experimental condition, the radiosensitization of paclitaxel-loaded nanoparticles was more significant than that of free paclitaxel.

Magnetite Nanoparticles Inhibit Tumor Growth and Upregulate the Expression of P53/P16 in Ehrlich Solid Carcinoma Bearing Mice

“…This proves that MNPs could successfully up taken by tumor tissues and more accumulated in tumor after IT injection. The observed slight increase in accumulated iron after IP treatment may be attributed to the reported ability of NPs to cross biological barriers such as blood vessel walls and cell membrane through endocytosis [33], [34]. The observed high accumulation of iron in tumor tissue after IT injection recommended the local administration which will be followed by tissue distribution as a result of the known enhanced permeability and retention (EPR) in tumor tissue and the perforated leaky tumoral blood vessels which allow molecules to accumulate passively in the tumor microenvironment [35].…”

Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer

“…Potential candidates could be different quantum dots and nanoparticles (though most of them not tested yet with ionizing radiation and listed as possible candidates): CaF [161], LaF [162], ZnS [163] or ZnO [164] quantum dots, carbon dots [55], liposomes loaded with hypoxic radiosensitizer ethanidazole [165,166] or paclitaxel [166,167], DNA cross-linker cisplatin [168], nanoparticle-photosensitizer conjugates [2], silicon nanoparticles [52], liposomes loaded with antioxidants such as catechines [169,170], theanines [171,172] and curcumin [173,174], liposomes with entrapped radiosensitizers such as porphyrins [175–177]. …”

Silver Nanocrystals Mediated Combination Therapy of Radiation with Magnetic Hyperthermia on Glioma Cells

“…In cancer radiotherapy, nanostructure combined the drug for enhancing radiation-induced killing of cancer cells has been designed. [7][8][9] However, in these experiments performed, the drugs play the role to kill or enhance the therapeutic effect on cancer cells, and the nanostructures do act as vectors and not induce cell apoptosis or death per se.…”