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. Author manuscript; available in PMC: 2015 May 1.

Published in final edited form as: Nat Nanotechnol. 2014 Oct 5;9(11):907–912. doi: 10.1038/nnano.2014.208

Fig. 4 — a, BT-474 (human breast cancer cell) growth inhibitory effects by control (untreated), Herceptin (0.5 mg ml⁻¹), Herceptin-MNC (Herceptin/OEGCG/PEG-EGCG = 0.5/0.024/0.26 mg ml⁻¹), BSA-MNC (drug-free carrier, with the equivalents), a mixture of BSA-MNC and Herceptin (with the equivalents), BSA (with the equivalent), OEGCG and PEG-EGCG (carrier components, with the equivalents). Herceptin-MNC showed a higher cancer cell growth inhibitory effect than free Herceptin via synergism of the inhibitory effects of the carrier and Herceptin. n = 5 (mean ± s.d.), ***p < 0.001. b, Anticancer effect on BT-474-xenografted nude mouse model. PBS (vehicle control, white circles), BSA-MNC (white triangles), Herceptin (2.5 mg kg⁻¹, white squares), sequential injection of BSA-MNC and Herceptin (black inverted triangles), and Herceptin-MNC (black circles) in the same formulations as those used in Fig. 4a. Herceptin-MNC showed a significantly higher anticancer effect than sequentially injected BSA-MNC and Herceptin, as well as free Herceptin. n = 12 (mean ± s.d.), *p < 0.05, **p < 0.01, ****p < 0.0001. c, Real-time intraoperative tumour detection and NIR fluorescence image-guided resection at 24 h post-injection. Arrows = nonspecific uptake (liver, kidneys, intestine); red dotted circle = ROI; T (+), positive tumour; He, heart; Lu, lung; Li, liver; Pa, pancreas; Sp, spleen; Ki, kidneys; Du, duodenum; In, intestine; Mu, muscle. Scale bars = 1 cm. d, Biodistribution of Herceptin (white bars) and Herceptin-MNC (black bars) in major organs measured at 24 h post-injection. Herceptin-MNC exhibited 2.3-fold higher accumulation in tumour and 0.3-, 0.3- and 0.6-fold lower accumulation in liver, kidney and lung, respectively, as compared to free Herceptin at 24 h post-injection. n = 5 (mean ± s.d.), *p < 0.05. e, Tumour-to-background (normal organ/tissue) ratio for Herceptin (white bars) and Herceptin-MNC (black bars) at 24 h post-injection. Herceptin-MNC showed the improved tumour selectivity to surrounding normal organs/tissues, as compared to free Herceptin. n = 5 (mean ± s.d.), *p < 0.05, ***p < 0.001, Tu, tumour; Li, liver; Ki, kidney; Sp, spleen; Mu, muscle. f, H&E staining (left), targeted NIR fluorescence (middle,pseudocoloured in lime green), and immunofluorescence staining (right, pseudocoloured in red) images of BT-474 xenograft tumour at 24 h post-injection. Herceptin-MNCs were observed throughout the extravascular space, which was consistent with the localization of overexpressed HER2/neu receptors on the tumour, suggesting extravasation and deep tumour penetration of Herceptin-MNC. Scale bars = 100 μm. All NIR fluorescence images have identical exposure times and normalization.

Fig. 4 — a, BT-474 (human breast cancer cell) growth inhibitory effects by control (untreated), Herceptin (0.5 mg ml⁻¹), Herceptin-MNC (Herceptin/OEGCG/PEG-EGCG = 0.5/0.024/0.26 mg ml⁻¹), BSA-MNC (drug-free carrier, with the equivalents), a mixture of BSA-MNC and Herceptin (with the equivalents), BSA (with the equivalent), OEGCG and PEG-EGCG (carrier components, with the equivalents). Herceptin-MNC showed a higher cancer cell growth inhibitory effect than free Herceptin via synergism of the inhibitory effects of the carrier and Herceptin. n = 5 (mean ± s.d.), ***p < 0.001. b, Anticancer effect on BT-474-xenografted nude mouse model. PBS (vehicle control, white circles), BSA-MNC (white triangles), Herceptin (2.5 mg kg⁻¹, white squares), sequential injection of BSA-MNC and Herceptin (black inverted triangles), and Herceptin-MNC (black circles) in the same formulations as those used in Fig. 4a. Herceptin-MNC showed a significantly higher anticancer effect than sequentially injected BSA-MNC and Herceptin, as well as free Herceptin. n = 12 (mean ± s.d.), *p < 0.05, **p < 0.01, ****p < 0.0001. c, Real-time intraoperative tumour detection and NIR fluorescence image-guided resection at 24 h post-injection. Arrows = nonspecific uptake (liver, kidneys, intestine); red dotted circle = ROI; T (+), positive tumour; He, heart; Lu, lung; Li, liver; Pa, pancreas; Sp, spleen; Ki, kidneys; Du, duodenum; In, intestine; Mu, muscle. Scale bars = 1 cm. d, Biodistribution of Herceptin (white bars) and Herceptin-MNC (black bars) in major organs measured at 24 h post-injection. Herceptin-MNC exhibited 2.3-fold higher accumulation in tumour and 0.3-, 0.3- and 0.6-fold lower accumulation in liver, kidney and lung, respectively, as compared to free Herceptin at 24 h post-injection. n = 5 (mean ± s.d.), *p < 0.05. e, Tumour-to-background (normal organ/tissue) ratio for Herceptin (white bars) and Herceptin-MNC (black bars) at 24 h post-injection. Herceptin-MNC showed the improved tumour selectivity to surrounding normal organs/tissues, as compared to free Herceptin. n = 5 (mean ± s.d.), *p < 0.05, ***p < 0.001, Tu, tumour; Li, liver; Ki, kidney; Sp, spleen; Mu, muscle. f, H&E staining (left), targeted NIR fluorescence (middle,pseudocoloured in lime green), and immunofluorescence staining (right, pseudocoloured in red) images of BT-474 xenograft tumour at 24 h post-injection. Herceptin-MNCs were observed throughout the extravascular space, which was consistent with the localization of overexpressed HER2/neu receptors on the tumour, suggesting extravasation and deep tumour penetration of Herceptin-MNC. Scale bars = 100 μm. All NIR fluorescence images have identical exposure times and normalization.