Encapsulation in Nanoparticles Improves Anti-cancer Efficacy of Carboplatin

Abstract

Poor cellular uptake contributes to high dose requirement and limited therapeutic efficacy of the platinum-based anticancer drug carboplatin. Delivery systems that can improve the cellular accumulation of carboplatin will, therefore, likely improve its therapeutic potential. The objective of this study was to evaluate nanoparticles composed of the biodegradable polymer, poly(D, L-lactide-co-glycolide), for carboplatin delivery to tumor cells. Carboplatin-loaded nanoparticles were formulated by double emulsion-solvent evaporation technique. Nanoparticles demonstrated sustained release of carboplatin over 7 days. Cellular uptake of carboplatin encapsulated in nanoparticles was several fold higher than that with free carboplatin in A549 (lung) and MA148 (ovarian) tumor cells. In vitro cytotoxicity studies showed that encapsulation of carboplatin in nanoparticles resulted in a remarkable reduction in the IC50 of carboplatin in several cell lines (up to 280-fold in some cells). Confocal microscopic analysis revealed the presence of carboplatin nanoparticles in several cellular compartments including lysosomes, cytoplasm, and the nucleus. These results demonstrate an enhanced cellular uptake of carboplatin through encapsulation in PLGA nanoparticles and suggest that improved therapeutic efficacy and reduced toxicity may be achieved with this approach.

Nano-engineered mesenchymal stem cells as targeted therapeutic carriers

“…We initially optimized the conditions for nanoparticle loading in MSCs by evaluating the effect of dose of nanoparticles and the duration of incubation. These studies suggested that the maximal uptake of nanoparticles occurred after incubation with 100 μg/ml of nanoparticles for 4-6 h. Similar to what has been reported earlier in other cells [32], nanoparticles were found co-localized in the lysosomes (yellow) and also present free in the cytosol (green) (Supplementary Fig. 4).…”

Nanotechnology for mesenchymal stem cell therapies

“…However, the potential of MSC to home toward the site of injury has exploited them as suitable tools to carry nanomaterials (mainly nanoparticles) for diagnostic and therapeutic purposes [115,116]. For example, the use of fluorescent/magnetic nanoparticles has improved the efficacy of stem cell-based therapies.…”

Repurposing platinum-based chemotherapies for multi-modal treatment of glioblastoma

“…56 Moreover, NP formulations of carboplatin compounds are capable of providing controlled release of the drug for more than a week. 69 Although sustained release can be achieved through numerous biomaterial formulation strategies, NPs can be designed to enable brain-penetration and tumor targeting, 48,70 potentially improving treatment for invasive brain tumors, like GBM. Furthermore, free platinum drugs have a limited half-life in most tissues.…”