Fig. 2.

ADNMs Were Effective for Drug Delivery and Inhibiting Tumor Growth via Specific Accumulation and Deep Penetration in Tumor. (A) Chemical structure of the AD, and the anticancer drugs DOX, PTX and R used in this study. (B) Small and spherical nanoparticles of the ADNM-based DDSs observed under transmission electron microscope (TEM). DOX/AD, PTX/AD and R/AD refer to DOX-, PTX- and R-loaded ADNMs, respectively. (C) Tumor growth curves of the patient-derived pancreatic cancer xenografts PDAC087T and PDAC074T, and the colorectal cancer HCT-8 xenografts in mice upon treatment with DOX/AD and R/AD, respectively. Mice treated with PBS buffer, drug alone or dendrimer alone were used as the controls. Data are presented as the mean ± SEM. The statistical significance was calculated by two-way ANOVA with a Tukey's multiple comparisons test. n = 6 mice for all groups. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. (D) Accumulation of R/AD in tumors in the PDAC074T and HCT-8 xenograft mice was analyzed using fluorescent imaging with ADNM carrying both rapamycin and the near-infrared fluorescent dye DiR (DiR/R/AD). The in vivo fluorescence images were acquired 48 h after intravenous administration of DiR/R/AD in PDAC074T (Upper) and HCT-8 (Lower) xenografts. Mice treated with PBS, free DiR, and a simple mixture of DiR, rapamycin and AD (DiR + R + AD), were used as controls. Arrows point to the tumor locations. (E) Confocal images of tumor tissues show a deep intratumoral penetration of R/AD, using ADNM loaded with both rapamycin and the fluorescent dye DiI (DiI/R/AD). Mice treated with PBS, DiI alone, or a simple mixture of DiI, rapamycin and AD (DiI + R + AD), were used as controls. Tumors were harvested from PDAC074T (Left) and HCT-8 (Right) xenografts 24 h post-intravenous administration, then cryosectioned and imaged by tracing DiI fluorescence (red). Blood vessels were labelled with DyLight488-labeled Lycopersicon esculentum lectin (green), and nuclei with DAPI (blue).