Intracellular Uptake and Distribution of Block-Copolymer Cross-Linked Nanoassemblies

Nanoscale particles, 20-200 nanometers in diameter, have emerged in recent biomedical applications as promising carriers that deliver various active agents to targeted tissues in vivo in a controlled manner. However, controlling interactions between the nanoparticles and cells and potentially targeting intracellular organelles for customized therapy have not been fully achieved due to limited understanding about the effect of colloidal stability on intracellular uptake and distribution patterns of nanoparticles. Nanoparticle drug carriers with different stability may alter the overall drug uptake kinetics and accumulation in organelles inside live cells, including cancerous cells, resulting in differential cellular response to the drug. To test this hypothesis, human colon (HT29) and breast cancer (MCF7) cells were treated with previously synthesized poly(ethylene glycol)-poly(aspartate) based crosslinked nanoassemblies (CNAs) and self-assembled nanoassemblies (SNAs). CNAs entered cells as early as 15 minutes and their accumulation in cell nuclei continued to increase for 24 hours, while HT29 cells took up the nanoparticles more efficiently than MCF7. On the contrary, SNAs showed almost no cellular uptake in HT29 cells. Experimental data from this study suggest that stable nanoparticles (CNAs) would be more efficient to carry payloads into cells compared to dissociable block copolymer assemblies (SNAs).