Sonoporation enhances liposome accumulation and penetration in tumors with low EPR

B. Theek, M. Baues, T. Ojha, D. Möckel, S.K. Veettil, J. Steitz, L. van Bloois, Gerrit Storm, F. Kiessling, Twan Gerardus Gertudis Maria Lammers

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

The Enhanced Permeability and Retention (EPR) effect is a highly variable phenomenon. To enhance EPR-mediated passive drug targeting to tumors, several different pharmacological and physical strategies have been evaluated over the years, including e.g. TNFα-treatment, vascular normalization, hyperthermia and radiotherapy. Here, we systematically investigated the impact of sonoporation, i.e. the combination of ultrasound (US) and microbubbles (MB), on the tumor accumulation and penetration of liposomes. Two different MB formulations were employed, and their ability to enhance liposome accumulation and penetration was evaluated in two different tumor models, which are both characterized by relatively low levels of EPR (i.e. highly cellular A431 epidermoid xenografts and highly stromal BxPC-3 pancreatic carcinoma xenografts). The liposomes were labeled with two different fluorophores, enabling in vivo computed tomography/fluorescence molecular tomography (CT-FMT) and ex vivo two-photon laser scanning microscopy (TPLSM). In both models, in spite of relatively high inter- and intra-individual variability, a trend towards improved liposome accumulation and penetration was observed. In treated tumors, liposome concentrations were up to twice as high as in untreated tumors, and sonoporation enhanced the ability of liposomes to extravasate out of the blood vessels into the tumor interstitium. These findings indicate that sonoporation may be a useful strategy for improving drug targeting to tumors with low EPR.
Original languageEnglish
Pages (from-to)77-85
JournalJournal of controlled release
Volume231
DOIs
Publication statusPublished - 2016

Fingerprint

Liposomes
Permeability
Microbubbles
Neoplasms
Drug Delivery Systems
Heterografts
Tomography
Vascular Tissue Neoplasms
Photons
Confocal Microscopy
Blood Vessels
Fever
Radiotherapy
Fluorescence
Pharmacology

Keywords

  • IR-103919
  • METIS-320793

Cite this

Theek, B. ; Baues, M. ; Ojha, T. ; Möckel, D. ; Veettil, S.K. ; Steitz, J. ; van Bloois, L. ; Storm, Gerrit ; Kiessling, F. ; Lammers, Twan Gerardus Gertudis Maria. / Sonoporation enhances liposome accumulation and penetration in tumors with low EPR. In: Journal of controlled release. 2016 ; Vol. 231. pp. 77-85.
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abstract = "The Enhanced Permeability and Retention (EPR) effect is a highly variable phenomenon. To enhance EPR-mediated passive drug targeting to tumors, several different pharmacological and physical strategies have been evaluated over the years, including e.g. TNFα-treatment, vascular normalization, hyperthermia and radiotherapy. Here, we systematically investigated the impact of sonoporation, i.e. the combination of ultrasound (US) and microbubbles (MB), on the tumor accumulation and penetration of liposomes. Two different MB formulations were employed, and their ability to enhance liposome accumulation and penetration was evaluated in two different tumor models, which are both characterized by relatively low levels of EPR (i.e. highly cellular A431 epidermoid xenografts and highly stromal BxPC-3 pancreatic carcinoma xenografts). The liposomes were labeled with two different fluorophores, enabling in vivo computed tomography/fluorescence molecular tomography (CT-FMT) and ex vivo two-photon laser scanning microscopy (TPLSM). In both models, in spite of relatively high inter- and intra-individual variability, a trend towards improved liposome accumulation and penetration was observed. In treated tumors, liposome concentrations were up to twice as high as in untreated tumors, and sonoporation enhanced the ability of liposomes to extravasate out of the blood vessels into the tumor interstitium. These findings indicate that sonoporation may be a useful strategy for improving drug targeting to tumors with low EPR.",
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author = "B. Theek and M. Baues and T. Ojha and D. M{\"o}ckel and S.K. Veettil and J. Steitz and {van Bloois}, L. and Gerrit Storm and F. Kiessling and Lammers, {Twan Gerardus Gertudis Maria}",
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Theek, B, Baues, M, Ojha, T, Möckel, D, Veettil, SK, Steitz, J, van Bloois, L, Storm, G, Kiessling, F & Lammers, TGGM 2016, 'Sonoporation enhances liposome accumulation and penetration in tumors with low EPR' Journal of controlled release, vol. 231, pp. 77-85. https://doi.org/10.1016/j.jconrel.2016.02.021

Sonoporation enhances liposome accumulation and penetration in tumors with low EPR. / Theek, B.; Baues, M.; Ojha, T.; Möckel, D.; Veettil, S.K.; Steitz, J.; van Bloois, L.; Storm, Gerrit; Kiessling, F.; Lammers, Twan Gerardus Gertudis Maria.

In: Journal of controlled release, Vol. 231, 2016, p. 77-85.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Sonoporation enhances liposome accumulation and penetration in tumors with low EPR

AU - Theek, B.

AU - Baues, M.

AU - Ojha, T.

AU - Möckel, D.

AU - Veettil, S.K.

AU - Steitz, J.

AU - van Bloois, L.

AU - Storm, Gerrit

AU - Kiessling, F.

AU - Lammers, Twan Gerardus Gertudis Maria

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PY - 2016

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N2 - The Enhanced Permeability and Retention (EPR) effect is a highly variable phenomenon. To enhance EPR-mediated passive drug targeting to tumors, several different pharmacological and physical strategies have been evaluated over the years, including e.g. TNFα-treatment, vascular normalization, hyperthermia and radiotherapy. Here, we systematically investigated the impact of sonoporation, i.e. the combination of ultrasound (US) and microbubbles (MB), on the tumor accumulation and penetration of liposomes. Two different MB formulations were employed, and their ability to enhance liposome accumulation and penetration was evaluated in two different tumor models, which are both characterized by relatively low levels of EPR (i.e. highly cellular A431 epidermoid xenografts and highly stromal BxPC-3 pancreatic carcinoma xenografts). The liposomes were labeled with two different fluorophores, enabling in vivo computed tomography/fluorescence molecular tomography (CT-FMT) and ex vivo two-photon laser scanning microscopy (TPLSM). In both models, in spite of relatively high inter- and intra-individual variability, a trend towards improved liposome accumulation and penetration was observed. In treated tumors, liposome concentrations were up to twice as high as in untreated tumors, and sonoporation enhanced the ability of liposomes to extravasate out of the blood vessels into the tumor interstitium. These findings indicate that sonoporation may be a useful strategy for improving drug targeting to tumors with low EPR.

AB - The Enhanced Permeability and Retention (EPR) effect is a highly variable phenomenon. To enhance EPR-mediated passive drug targeting to tumors, several different pharmacological and physical strategies have been evaluated over the years, including e.g. TNFα-treatment, vascular normalization, hyperthermia and radiotherapy. Here, we systematically investigated the impact of sonoporation, i.e. the combination of ultrasound (US) and microbubbles (MB), on the tumor accumulation and penetration of liposomes. Two different MB formulations were employed, and their ability to enhance liposome accumulation and penetration was evaluated in two different tumor models, which are both characterized by relatively low levels of EPR (i.e. highly cellular A431 epidermoid xenografts and highly stromal BxPC-3 pancreatic carcinoma xenografts). The liposomes were labeled with two different fluorophores, enabling in vivo computed tomography/fluorescence molecular tomography (CT-FMT) and ex vivo two-photon laser scanning microscopy (TPLSM). In both models, in spite of relatively high inter- and intra-individual variability, a trend towards improved liposome accumulation and penetration was observed. In treated tumors, liposome concentrations were up to twice as high as in untreated tumors, and sonoporation enhanced the ability of liposomes to extravasate out of the blood vessels into the tumor interstitium. These findings indicate that sonoporation may be a useful strategy for improving drug targeting to tumors with low EPR.

KW - IR-103919

KW - METIS-320793

U2 - 10.1016/j.jconrel.2016.02.021

DO - 10.1016/j.jconrel.2016.02.021

M3 - Article

VL - 231

SP - 77

EP - 85

JO - Journal of controlled release

JF - Journal of controlled release

SN - 0168-3659

ER -