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Beyond the imaging: limitations of cellular uptake study in the evaluation of nanoparticles.

ABSTRACT: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) conjugated to a cell-penetrating peptide, TAT, was used to increase intracellular delivery of paclitaxel (PTX) to multi-drug resistant (MDR) cells. Efficient cellular uptake of the TAT-conjugated PLGA NPs was observed; however, it did not translate to increased killing of MDR cells. An investigation of drug release kinetics in phosphate-buffered saline containing Tween 80 led us to suspect that a significant fraction of the loaded PTX was released before efficient cellular uptake could occur. These results indicate that the increased cellular uptake of NPs does not always mean an enhanced drug effect and that it is critical to control both the location of NPs and the drug release from NPs together. Based on this study, we propose that two prevalent practices in NP research be reconsidered: first, the utility of a new NP system should be tested beyond the imaging level. Second, NP release kinetics should be monitored in a medium that can reflect the complexity of biological environment rather than a simple buffered saline.

SUBMITTER: Gullotti E

PROVIDER: S-EPMC3447109 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Beyond the imaging: limitations of cellular uptake study in the evaluation of nanoparticles.

Gullotti Emily E Yeo Yoon Y

Journal of controlled release : official journal of the Controlled Release Society 20120505 2

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) conjugated to a cell-penetrating peptide, TAT, was used to increase intracellular delivery of paclitaxel (PTX) to multi-drug resistant (MDR) cells. Efficient cellular uptake of the TAT-conjugated PLGA NPs was observed; however, it did not translate to increased killing of MDR cells. An investigation of drug release kinetics in phosphate-buffered saline containing Tween 80 led us to suspect that a significant fraction of the loaded PTX was ...[more]

PMID: 22568932

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Project description:Magnetococcus marinus magnetosome-associated protein MamC, expressed as recombinant, has been proven to mediate the formation of novel biomimetic magnetic nanoparticles (BMNPs) that are successful drug nanocarriers for targeted chemotherapy and hyperthermia agents. These BMNPs present several advantages over inorganic magnetic nanoparticles, such as larger sizes that allow the former to have larger magnetic moment per particle, and an isoelectric point at acidic pH values, which allows both the stable functionalization of BMNPs at physiological pH value and the molecule release at acidic (tumor) environments, simply based on electrostatic interactions. However, difficulties for BMNPs cell internalization still hold back the efficiency of these nanoparticles as drug nanocarriers and hyperthermia agents. In the present study we explore the enhanced BMNPs internalization following upon their encapsulation by poly (lactic-co-glycolic) acid (PLGA), a Food and Drug Administration (FDA) approved molecule. Internalization is further optimized by the functionalization of the nanoformulation with the cell-penetrating TAT peptide (TATp). Our results evidence that cells treated with the nanoformulation [TAT-PLGA(BMNPs)] show up to 80% more iron internalized (after 72 h) compared to that of cells treated with BMNPs (40%), without any significant decrease in cell viability. This nanoformulation showing optimal internalization is further characterized. In particular, the present manuscript demonstrates that neither its magnetic properties nor its performance as a hyperthermia agent are significantly altered due to the encapsulation. In vitro experiments demonstrate that, following upon the application of an alternating magnetic field on U87MG cells treated with BMNPs and TAT-PLGA(BMNPs), the cytotoxic effect of BMNPs was not affected by the TAT-PLGA enveloping. Based on that, difficulties shown in previous studies related to poor cell uptake of BMNPs can be overcome by the novel nanoassembly described here.

Dataset Information

Beyond the imaging: limitations of cellular uptake study in the evaluation of nanoparticles.

Publications

Beyond the imaging: limitations of cellular uptake study in the evaluation of nanoparticles.

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