Cancer-targeting ultrasmall silica nanoparticles for clinical translation: Physicochemical structure and biological property correlations Journal Article
| Authors: | Chen, F.; Ma, K.; Benezra, M.; Zhang, L.; Cheal, S. M.; Phillips, E.; Yoo, B.; Pauliah, M.; Overholtzer, M.; Zanzonico, P.; Sequeira, S.; Gonen, M.; Quinn, T.; Wiesner, U.; Bradbury, M. S. |
| Article Title: | Cancer-targeting ultrasmall silica nanoparticles for clinical translation: Physicochemical structure and biological property correlations |
| Abstract: | Although a large body of literature exists on the potential use of nanoparticles for medical applications, the number of probes translated into human clinical trials is remarkably small. A major challenge of particle probe development and their translation is the elucidation of safety profiles associated with their structural complexity, not only in terms of size distribution and heterogeneities in particle composition but also their effects on biological activities and the relationship between particle structure and pharmacokinetics. Here, we report on the synthesis, characterization, and long-term stability of ultrasmall (<10 nm diameter) dual-modality (optical and positron emission tomography) and integrin-targeting silica nanoparticles (cRGDY-PEG-Cy5-C′ dots and 124I-(or 131I-) cRGDY-PEG-Cy5-C′dots) and the extent to which their surface ligand density differentially modulates key in vitro and in vivo biological activities in melanoma models over a range of ligand numbers (i.e., ∼6-18). Gel permeation chromatography, established as an important particle characterization tool, revealed a two-year shelf life for cRGDY-PEG-Cy5-C′ dots. Radiochromatography further demonstrated the necessary radiochemical stability for clinical applications. The results of subsequent ligand density-dependent studies elucidate strong modulations in biological response, including statistically significant increases in integrin-specific targeting and particle uptake, cellular migration and adhesion, renal clearance, and tumor-to-blood ratios with increasing ligand number. We anticipate that nanoprobe characteristics and a better understanding of the structure-function relationships determined in this study will help guide identification of other lead nanoparticle candidates for in vitro and in vivo biological assessments and product translation. © 2017 American Chemical Society. |
| Keywords: | positron emission tomography; bioactivity; ligands; nanoparticles; probes; silica; synthesis (chemical); chelation; structure-function relationship; medical applications; clinical translation; biological properties; chromatography; gel permeation chromatography; biological assessment; particle characterization; particle composition; radiochemical stability; structural complexity |
| Journal Title: | Chemistry of Materials |
| Volume: | 29 |
| Issue: | 20 |
| ISSN: | 0897-4756 |
| Publisher: | American Chemical Society |
| Date Published: | 2017-10-24 |
| Start Page: | 8766 |
| End Page: | 8779 |
| Language: | English |
| DOI: | 10.1021/acs.chemmater.7b03033 |
| PROVIDER: | scopus |
| PUBMED: | 29129959 |
| PMCID: | PMC5679295 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2017 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work