HMR-1275 site Rhodamine B conjugated Gd-G8 dendrimers (n = 2). There is substantial extravasation of
Rhodamine B conjugated Gd-G8 dendrimers (n = 2). There is substantial extravasation of rhodamine B conjugated Gd-G5 dendrimers across the BBTB, which is more pronounced than that of Gd-G5 dendrimers across the BBTB. There is also some extravasation of rhodamine B conjugated Gd-G8 dendrimers across the BBTB, which is not the case for Gd-G8 dendrimers. D) Ex vivo low power fluorescence microscopy of RG-2 glioma tumor and surrounding brain tissue harvested at 2 hours following the intravenous bolus of rhodamine PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28607003 B conjugated Gd-G5 dendrimers. There is substantial accumulation of rhodamine B conjugated Gd-G5 dendrimers within tumor tissue, and some in surrounding normal brain tissue (left, T = tumor, N = normal, scale bar = 100 m). High power image of RG-glioma tumor PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28494239 shows subcellular localization of rhodamine B conjugated Gd-G5 dendrimers within individual RG-2 malignant glioma cells (upper right, scale bar = 20 m). H E stain of tumor and surrounding brain (lower right, scale bar = 100 m). Tumor volume is 31 mm3. E) Ex vivo low power fluorescence microscopy of RG-2 glioma tumor and surrounding brain tissue harvested at 2 hours following the intravenous bolus of rhodamine B conjugated Gd-G8 dendrimers. There is some minimal accumulation of rhodamine B conjugated Gd-G8 dendrimers within brain tumor tissue (left, T = tumor, N = normal, scale bar = 100 m). High power confirms there is some minimal subcellular localization of rhodamine B conjugated Gd-G8 dendrimers within individual RG-2 glioma cells (upper right, scale bar = 20 m). H E stain of tumor and surrounding brain (lower right, scale bar = 100 m). Tumor volume is 30 mm3. Rhodamine B conjugated Gd-G5 dendrimers and rhodamine B conjugated Gd-G8 dendrimers administered intravenously over 1 minute at a Gd dose of 0.06 mmol Gd/kg animal body weight. Adapted from reference[73].Page 8 of(page number not for citation purposes)Journal of Translational Medicine 2009, 7:http://www.translational-medicine.com/content/7/1/Figure 5 dendrimer The prototype of an imageable nanoparticle bearing chemotherapy within the 7 to 10 nm size range: The Gd-G5-doxorubicin The prototype of an imageable nanoparticle bearing chemotherapy within the 7 to 10 nm size range: The GdG5-doxorubicin dendrimer. A) An illustration of the Gd-G5-doxorubicin dendrimer. Doxorubicin is conjugated to the dendrimer terminal amines by a pH-sensitive hydrazone bond, which facilitates the rapid release of doxorubicin following particle endocytosis into brain tumor cell lysosomal compartments. B) Annular dark-field scanning transmission electron microscopy image of Gd-G5-doxorubicin dendrimers. C) In vitro fluorescence microscopy of cultured RG-2 glioma cells incubated for 4 hours in media containing Gd-G5-doxorubicin dendrimers at a 600 nM concentration. The red fluorescence in the cytoplasm represents Gd-G5-doxorubicin dendrimers within the cytoplasm of RG-2 glioma cells. The red fluorescence within the RG-2 cell nuclei represents free doxorubicin that has been released from the Gd-G5-doxorubicn dendrimers following cleavage of the hydrazone bond, since particles larger than Gd-G2 dendrimers are too large to pass through the nuclear pores. D) T2weighted anatomic scan image and T1-weighted dynamic contrast-enhanced MRI scan Gd concentration map images at various time points up to 60 minutes following Gd-G5-doxorubicn dendrimer infusion. The Gd-G5-doxorubicin dendrimer was administered intravenously over 2 minutes at a Gd dose of 0.09 mm.

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