Fig. 6: Tests of tumor-agnostic delivery mechanism. | Nature Communications

Fig. 6: Tests of tumor-agnostic delivery mechanism.

From: Tumor agnostic drug delivery with dynamic nanohydrogels

Fig. 6: Tests of tumor-agnostic delivery mechanism.

a Representative phase contrast transmission electron microscopy (TEM) image showing reversible SANG agglomeration when going from 52 nM to 156 nM, and back again (re-diluted), n = 3 independent experiments. b Observed (solid lines, data points = mean ± sd) and expected (dotted lines) size and number of SANGs particles over the entire concentration range studied by TEM within a standard area field of view (n = 3 replicates). c Hydrodynamic size distributions of SANGs at 52 nM and 156 nM concentrations (n = 3 independent experiments- Wyatt DLS). d Diffusion coefficients derived from diffusion-ordered NMR (DOSY) for 20 ms and 100 ms pulse sequences and T2 relaxation times across a 10-fold concentration range. e Sequence of representative liquid phase transmission electron microscopy (LP-TEM) images (full data in Supplementary Movie 4) showing two instances (outlined regions) of SANG agglomeration at 52 nM and the persistence of self-adhered particles at 156 nM (n = 3 replicates). f Representative high-resolution (63x) maximal projection confocal microscopic image of a colon tumor showing a merged view of both fluorescently labeled SANG populations and DAPI. Scatter plot of pixel-based colocalization analysis of representative areas (Costes randomization-based colocalization R = 0.87 ± 0.02, p < 0.001, n = 3 animals, 3 sections each); a value of 0.5 indicates purely random co-localization probability. g Representative high-resolution (63x) maximal projection confocal microscopic image of a healthy liver showing a merged view of both fluorescently labeled Qβ VLP populations and DAPI. Scatter plot of pixel-based colocalization analysis of representative areas (Costes randomization based colocalization R = 0.52 ± 0.02, p < 0.001, n = 3 animals, 3 sections each). h Graphical depiction of the provisional mechanism by which SANGs achieve preferential tumor by exploiting maladaptive vasculature observed uniquely in tumor microenvironments (bottom) compared to healthy vasculature (top). (*) indicates statistically significant differences between experimental groups as empirically derived from a hierarchical Bayesian model (stan_glm): 95% highest density intervals do not overlap between groupwise contrasts.

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