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Enhanced Therapeutic Epidermal Growth Factor Receptor (EGFR) Antibody Delivery via Pulsed Ultrasound with Targeting Microbubbles for Glioma Treatment.

Liao AH, Chou HY, Hsieh YL, Hsu SC, Wei KC, Liu HL - J Med Biol Eng (2015)

Bottom Line: Three animal groups were compared: (1) IV-injected non-targeting MBs, (2) IV-injected targeting MBs, and (3) IV-injected targeting MBs combined with pUS treatment.The mean halftime of circulating targeting MBs was significantly increased from 3.13 min of targeting bubble alone to 5.86 min by targeting MBs combined with pUS treatment, compared to 2.34 min for non-targeting MBs.Compared to targeting bubble administration alone, pUS exposure prior to injection of targeting MBs was also significantly better at suppressing tumor growth when monitored for up to 35 days (p < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, 106 Taiwan.

ABSTRACT

Pulsed-mode ultrasound (pUS) in combination with intravenously (IV) administered microbubbles (MBs) can enhance local drug delivery by temporarily enhancing capillary permeability. This study evaluates the use of epidermal growth factor receptor (EGFR)-targeting MBs after pUS treatment to enhance the effects of therapeutic-EGFR antibody delivery to glioma tumor cells in mice. Three animal groups were compared: (1) IV-injected non-targeting MBs, (2) IV-injected targeting MBs, and (3) IV-injected targeting MBs combined with pUS treatment. All animals were analyzed using high-frequency small-animal US imaging. The mean halftime of circulating targeting MBs was significantly increased from 3.13 min of targeting bubble alone to 5.86 min by targeting MBs combined with pUS treatment, compared to 2.34 min for non-targeting MBs. Compared to targeting bubble administration alone, pUS exposure prior to injection of targeting MBs was also significantly better at suppressing tumor growth when monitored for up to 35 days (p < 0.05). The final relative tumor volumes were 2664, 700, and 188 mm(3) for non-targeting MBs, targeting MBs, and targeting MBs combined with pUS treatment, respectively. pUS treatment prolonged the mean circulatory halftime of targeting MBs and enhanced the anti-tumor effect of EGFR antibodies in a human glioma model in mice. Targeting MBs combined with pUS treatment thus has potential for enhanced therapeutic antibody delivery for facilitating anti-glioma treatment.

No MeSH data available.


Related in: MedlinePlus

Histopathologic analysis. a–c Qualitative assessment of immunohistochemical staining (IHC; upper row) demonstrating low EGFR in non-targeting MB treatment group (b), and high EGFR intensity in tumor vessels of targeting MB treatment group in both tumor vessels and tissues of targeting MB combined with pUS treatment group (c); d–f HE staining revealing similar histology in all three treatment groups
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Fig9: Histopathologic analysis. a–c Qualitative assessment of immunohistochemical staining (IHC; upper row) demonstrating low EGFR in non-targeting MB treatment group (b), and high EGFR intensity in tumor vessels of targeting MB treatment group in both tumor vessels and tissues of targeting MB combined with pUS treatment group (c); d–f HE staining revealing similar histology in all three treatment groups

Mentions: EGFR antibody delivery by various treatments was evaluated by immunohistochemistry at 35 days (Fig. 9a–c). Sections were also stained with HE (Fig. 9d–f). EGFR antibody was not observed in the control group (Fig. 9a). Targeting MBs in the absence of pUS treatment resulted in high levels of EGFR antibody deposition, located mostly inside vessels. In the targeted MB with pUS treatment group, EGFR antibody leaked outside vessels and spread through tumor tissues (Fig. 9c). pUS treatment clearly enhanced drug delivery (Fig. 9b versus Fig. 9c), without major histological changes (HE stain; Fig. 9e versus Fig. 9f).Fig. 9


Enhanced Therapeutic Epidermal Growth Factor Receptor (EGFR) Antibody Delivery via Pulsed Ultrasound with Targeting Microbubbles for Glioma Treatment.

Liao AH, Chou HY, Hsieh YL, Hsu SC, Wei KC, Liu HL - J Med Biol Eng (2015)

Histopathologic analysis. a–c Qualitative assessment of immunohistochemical staining (IHC; upper row) demonstrating low EGFR in non-targeting MB treatment group (b), and high EGFR intensity in tumor vessels of targeting MB treatment group in both tumor vessels and tissues of targeting MB combined with pUS treatment group (c); d–f HE staining revealing similar histology in all three treatment groups
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig9: Histopathologic analysis. a–c Qualitative assessment of immunohistochemical staining (IHC; upper row) demonstrating low EGFR in non-targeting MB treatment group (b), and high EGFR intensity in tumor vessels of targeting MB treatment group in both tumor vessels and tissues of targeting MB combined with pUS treatment group (c); d–f HE staining revealing similar histology in all three treatment groups
Mentions: EGFR antibody delivery by various treatments was evaluated by immunohistochemistry at 35 days (Fig. 9a–c). Sections were also stained with HE (Fig. 9d–f). EGFR antibody was not observed in the control group (Fig. 9a). Targeting MBs in the absence of pUS treatment resulted in high levels of EGFR antibody deposition, located mostly inside vessels. In the targeted MB with pUS treatment group, EGFR antibody leaked outside vessels and spread through tumor tissues (Fig. 9c). pUS treatment clearly enhanced drug delivery (Fig. 9b versus Fig. 9c), without major histological changes (HE stain; Fig. 9e versus Fig. 9f).Fig. 9

Bottom Line: Three animal groups were compared: (1) IV-injected non-targeting MBs, (2) IV-injected targeting MBs, and (3) IV-injected targeting MBs combined with pUS treatment.The mean halftime of circulating targeting MBs was significantly increased from 3.13 min of targeting bubble alone to 5.86 min by targeting MBs combined with pUS treatment, compared to 2.34 min for non-targeting MBs.Compared to targeting bubble administration alone, pUS exposure prior to injection of targeting MBs was also significantly better at suppressing tumor growth when monitored for up to 35 days (p < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, 106 Taiwan.

ABSTRACT

Pulsed-mode ultrasound (pUS) in combination with intravenously (IV) administered microbubbles (MBs) can enhance local drug delivery by temporarily enhancing capillary permeability. This study evaluates the use of epidermal growth factor receptor (EGFR)-targeting MBs after pUS treatment to enhance the effects of therapeutic-EGFR antibody delivery to glioma tumor cells in mice. Three animal groups were compared: (1) IV-injected non-targeting MBs, (2) IV-injected targeting MBs, and (3) IV-injected targeting MBs combined with pUS treatment. All animals were analyzed using high-frequency small-animal US imaging. The mean halftime of circulating targeting MBs was significantly increased from 3.13 min of targeting bubble alone to 5.86 min by targeting MBs combined with pUS treatment, compared to 2.34 min for non-targeting MBs. Compared to targeting bubble administration alone, pUS exposure prior to injection of targeting MBs was also significantly better at suppressing tumor growth when monitored for up to 35 days (p < 0.05). The final relative tumor volumes were 2664, 700, and 188 mm(3) for non-targeting MBs, targeting MBs, and targeting MBs combined with pUS treatment, respectively. pUS treatment prolonged the mean circulatory halftime of targeting MBs and enhanced the anti-tumor effect of EGFR antibodies in a human glioma model in mice. Targeting MBs combined with pUS treatment thus has potential for enhanced therapeutic antibody delivery for facilitating anti-glioma treatment.

No MeSH data available.


Related in: MedlinePlus