Delivery of Molecules to the Lymph Node via Lymphatic Vessels Using Ultrasound and Nano/Microbubbles

Kato, Shigekí; Shirai, Yuko; Kanzaki, Hiroyuki; Sakamoto, Maya; Mori, Shiro; Kodama, Tetsuya

doi:10.1016/j.ultrasmedbio.2014.12.014

Cited by 27 publications

(32 citation statements)

References 34 publications

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“…The concept is to inject drugs, before surgical resection, into upstream LNs within the dissection area, so that these drugs are delivered to downstream LNs outside the dissection area. To demonstrate proof of concept, we have developed MXH10/Mo-lpr/lpr (MXH10/Mo/lpr) inbred mice [1][2][3][4], and metastatic tumor cell lines able to grow in the mice. The phenotype of the lpr (lymphproliferation) gene is characterized by the accumulation of a large number of polyclonal CD4 -CD8 -T cells in the LNs and spleen [5]; the lpr gene is recognized as a "promoting factor" for collagen disease in MRL mice due to Fas-mediated apoptotic insufficiency, and the causative genes of collagen disease are considered to be the background genes of MRL mice [6].…”

Section: Introductionmentioning

confidence: 99%

Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system

Kodama

Hatakeyama

Kato

et al. 2014

Biomed. Opt. Express

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Curing/preventing micrometastasis to lymph nodes (LNs) located outside the surgically resected area is essential for improving the morbidity and mortality associated with breast cancer and head and neck cancer. However, no lymphatic therapy system exists that can deliver drugs to LNs located outside the dissection area. Here, we demonstrate proof of concept for a drug delivery system using MXH10/Mo-lpr/lpr mice that exhibit systemic lymphadenopathy, with some peripheral LNs being as large as 10 mm in diameter. We report that a fluorescent solution injected into the subiliac LN (defined as the upstream LN within the dissection area) was delivered successfully to the proper axillary LN (defined as the downstream LN outside the dissection area) through the lymphatic vessels. Our results suggest that this approach could be used before surgical resection to deliver drugs to downstream LNs outside the dissection area. We anticipate that our methodology could be applied clinically, before surgical resection, to cure/prevent micrometastasis in LNs outside the dissection area, using techniques such as ultrasound-guided internal jugular vein catheterization.

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Section: Introductionmentioning

confidence: 99%

Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system

Kodama

Hatakeyama

Kato

et al. 2014

Biomed. Opt. Express

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“…Therefore, there are two lymphatic routes to the subclavian vein in the axillary area: relatively uncommon . In previous experiments (Li et al, 2013a(Li et al, , 2013bKato et al, 2015;Kodama et al, 2015), we observed that fluorescent solution or ultrasound contrast agent injected into the SiLN seldom flowed across the midline to the contralateral side, and always flowed from the SiLN to the PALN. Thus, it is unlikely that the surgical procedure damaged the LVs that connected the SiLN and the PALN, or influenced the bifurcation patterns of the LV running between the SiLN and PALN.…”

Section: Discussionmentioning

confidence: 82%

Communication between lymphatic and venous systems in mice

Shao

Takeda

Kato

et al. 2015

Journal of Immunological Methods

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“…Cancer cells are easy to culture and to manipulate and therefore useful for fundamental studies. Finally, dendritic cells 14 or lymphocytes 22 are also interesting targets, e.g., for immunotherapy, since these can be reached directly from the blood stream or from the lymphatic nodes after subcutaneous injection and drainage of the microbubbles.…”

Section: Choice Of the Cell Modelmentioning

confidence: 99%

In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications

et al. 2016

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Besides their use as contrast agents for ultrasound imaging, microbubbles are increasingly studied for a wide range of therapeutic applications. In particular, their ability to enhance the uptake of drugs through the permeabilization of tissues and cell membranes shows great promise. In order to fully understand the numerous paths by which bubbles can interact with cells and the even larger number of possible biological responses from the cells, thorough and extensive work is necessary. In this review, we consider the range of experimental techniques implemented in in vitro studies with the aim of elucidating these microbubble-cell interactions. First of all, the variety of cell types and cell models available are discussed, emphasizing the need for more and more complex models replicating in vivo conditions together with experimental challenges associated with this increased complexity. Second, the different types of stabilized microbubbles and more recently developed droplets and particles are presented, followed by their acoustic or optical excitation methods. Finally, the techniques exploited to study the microbubble-cell interactions are reviewed. These techniques operate over a wide range of timescales, or even off-line, revealing particular aspects or subsequent effects of these interactions. Therefore, knowledge obtained from several techniques must be combined to elucidate the underlying processes. V C 2016 AIP Publishing LLC.

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Delivery of Molecules to the Lymph Node via Lymphatic Vessels Using Ultrasound and Nano/Microbubbles

Cited by 27 publications

References 34 publications

Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system

Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system

Communication between lymphatic and venous systems in mice

In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications

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