Tuning payload delivery in tumour cylindroids using gold nanoparticles

• Published in: Nature nanotechnology Vol. 5; no. 6; pp. 465 - 472
• Main Authors: Kim, Byoungjin, Han, Gang, Forbes, Neil S, Kim, Chae-kyu, Rotello, Vincent M, Toley, Bhushan J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-06-2010; Nature Publishing Group
• Subjects: 639/925/352/152; 639/925/352/2733; 639/925/357/354; Anions - chemistry; Anions - pharmacokinetics; Blood vessels; Cations - chemistry; Cations - pharmacokinetics; Cell Line, Tumor; Chemistry and Materials Science; Doxorubicin - pharmacokinetics; Drug Delivery Systems - methods; Fluorescein - pharmacokinetics; Fluorescence; Fluorescence microscopy; Gold - chemistry; Gold - pharmacokinetics; Humans; Least-Squares Analysis; Ligands; Materials Science; Metal Nanoparticles - chemistry; Microscopy; Microscopy, Fluorescence; Models, Biological; Nanoparticles; Nanotechnology; Nanotechnology and Microengineering; Neoplasms; Phantoms, Imaging; Tissues; Tumors; United States > US; Massachusetts
• ISSN: 1748-3387; 1748-3395
• DOI: 10.1038/nnano.2010.58

Nanoparticles have great potential as controllable drug delivery vehicles because of their size and modular functionality. Timing and location are important parameters when optimizing nanoparticles for delivery of chemotherapeutics. Here, we show that gold nanoparticles carrying either fluorescein or doxorubicin molecules move and localize differently in an
in vitro
three-dimensional model of tumour tissue, depending on whether the nanoparticles are positively or negatively charged. Fluorescence microscopy and mathematical modelling show that uptake, not diffusion, is the dominant mechanism in particle delivery. Our results indicate that positive particles may be more effective for drug delivery because they are taken up to a greater extent by proliferating cells. Negative particles, which diffuse more quickly, may perform better when delivering drugs deep into tissues. An understanding of how surface charge can control tissue penetration and drug release may overcome some of the current limitations in drug delivery.
In vitro
studies using three-dimensional tumour models and mathematical simulation show that positively charged particles are better for delivering therapeutics to viable cells, whereas negative particles are better when deep tissue penetration is required.