Price Lauren S L, Stern Stephan T, Deal Allison M, Kabanov Alexander V, Zamboni William C
Carolina Center of Cancer Nanotechnology Excellence (C-CCNE), University of North Carolina, Chapel Hill, NC, USA.
Translational Oncology and Nanoparticle Drug Development (TOND2I) Lab, University of North Carolina, Chapel Hill, NC, USA.
Sci Adv. 2020 Jul 15;6(29):eaay9249. doi: 10.1126/sciadv.aay9249. eCollection 2020 Jul.
Nanoparticle (NP) delivery to solid tumors has recently been questioned. To better understand the magnitude of NP tumor delivery, we reanalyzed published murine NP tumor pharmacokinetic (PK) data used in the Wilhelm . study. Studies included in their analysis reporting matched tumor and blood concentration versus time data were evaluated using classical PK endpoints and compared to the unestablished percent injected dose (%ID) in tumor metric from the Wilhelm . study. The %ID in tumor was poorly correlated with standard PK metrics that describe NP tumor delivery (AUC/AUC ratio) and only moderately associated with maximal tumor concentration. The relative tumor delivery of NPs was ~100-fold greater as assessed by the standard AUC/AUC ratio than by %ID in tumor. These results strongly suggest that PK metrics and calculations can influence the interpretation of NP tumor delivery and stress the need to properly validate novel PK metrics against traditional approaches.
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