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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

Conceptual diagram of this study. pUS beam was focused on glioma tumor. After injection of targeting MBs, US imaging was performed
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Fig1: Conceptual diagram of this study. pUS beam was focused on glioma tumor. After injection of targeting MBs, US imaging was performed

Mentions: The present study evaluates the potential of pUS exposure combined with therapeutic EGFR-targeting MB administration for glioma treatment (concepts shown in Fig. 1). It is hypothesized that pUS-MB exposure can enhance blood-tumor permeability and prolong the circulation of the targeting MBs and enhance the local concentration of therapeutic EGFR delivery at the local tumor site to provide therapeutic efficacy.Fig. 1


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)

Conceptual diagram of this study. pUS beam was focused on glioma tumor. After injection of targeting MBs, US imaging was performed
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4414932&req=5

Fig1: Conceptual diagram of this study. pUS beam was focused on glioma tumor. After injection of targeting MBs, US imaging was performed
Mentions: The present study evaluates the potential of pUS exposure combined with therapeutic EGFR-targeting MB administration for glioma treatment (concepts shown in Fig. 1). It is hypothesized that pUS-MB exposure can enhance blood-tumor permeability and prolong the circulation of the targeting MBs and enhance the local concentration of therapeutic EGFR delivery at the local tumor site to provide therapeutic efficacy.Fig. 1

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