Nanochannel implants for minimally-invasive insertion and intratumoral delivery

Research output: Contribution to journalArticle

R. Lyle Hood, Giacomo Bruno, Priya Jain, Jeff Anderson, Tatiana Wolfe, Caio Quini, Jeffery Schmulen, Xian C. Li, E. Brian Butler, Sunil Krishnan, Alessandro Grattoni

Novel approaches to achieve local, intratumoral drug delivery have the dual benefit of reducing systemic toxicity while enhancing efficacy for malignant cells. We have developed a new implantable system combining a next-generation BioNEMS nanofluidic membrane with parallel nanochannels that offers controlled release of biomolecules. Based on concentration-driven diffusive transport, nanochannel membranes provide a "drug agnostic" delivery mechanism. Integrating this nanotechnology within a small implantable capsule permits multipurpose functionality and compatibility with different therapeutic approaches as well as diagnostic imaging capability. A minimally-invasive, percutaneous trocar delivery mechanism enables serial implantation throughout a target tissue volume. In this manuscript, we demonstrate that this platform is capable of sustained delivery for chemotherapy, radiosensitization, immunomodulation, and imaging contrast, among others. This platform's utility was established through release of doxorubicin, OX86, FGK45, and Magnevist. Further proof-of-concept experiments demonstrated successful in vivo implantation and intratumoral release of antibodies and contrast agents, as well as the platform's MR-compatibility and capability as a radiopaque fiducial. These results provide strong evidence for a flexible, multifunctional nanofluidic implant capable of broadening local delivery utility in the clinic.

Original languageEnglish (US)
Pages (from-to)1907-1915
Number of pages9
JournalJournal of Biomedical Nanotechnology
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2016

PMID: 29360309

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Nanochannel implants for minimally-invasive insertion and intratumoral delivery. / Hood, R. Lyle; Bruno, Giacomo; Jain, Priya; Anderson, Jeff; Wolfe, Tatiana; Quini, Caio; Schmulen, Jeffery; Li, Xian C.; Butler, E. Brian; Krishnan, Sunil; Grattoni, Alessandro.

In: Journal of Biomedical Nanotechnology, Vol. 12, No. 10, 01.10.2016, p. 1907-1915.

Research output: Contribution to journalArticle

Harvard

Hood, RL, Bruno, G, Jain, P, Anderson, J, Wolfe, T, Quini, C, Schmulen, J, Li, XC, Butler, EB, Krishnan, S & Grattoni, A 2016, 'Nanochannel implants for minimally-invasive insertion and intratumoral delivery' Journal of Biomedical Nanotechnology, vol. 12, no. 10, pp. 1907-1915. https://doi.org/10.1166/jbn.2016.2288

APA

Hood, R. L., Bruno, G., Jain, P., Anderson, J., Wolfe, T., Quini, C., ... Grattoni, A. (2016). Nanochannel implants for minimally-invasive insertion and intratumoral delivery. Journal of Biomedical Nanotechnology, 12(10), 1907-1915. https://doi.org/10.1166/jbn.2016.2288

Vancouver

Hood RL, Bruno G, Jain P, Anderson J, Wolfe T, Quini C et al. Nanochannel implants for minimally-invasive insertion and intratumoral delivery. Journal of Biomedical Nanotechnology. 2016 Oct 1;12(10):1907-1915. https://doi.org/10.1166/jbn.2016.2288

Author

Hood, R. Lyle ; Bruno, Giacomo ; Jain, Priya ; Anderson, Jeff ; Wolfe, Tatiana ; Quini, Caio ; Schmulen, Jeffery ; Li, Xian C. ; Butler, E. Brian ; Krishnan, Sunil ; Grattoni, Alessandro. / Nanochannel implants for minimally-invasive insertion and intratumoral delivery. In: Journal of Biomedical Nanotechnology. 2016 ; Vol. 12, No. 10. pp. 1907-1915.

BibTeX

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title = "Nanochannel implants for minimally-invasive insertion and intratumoral delivery",
abstract = "Novel approaches to achieve local, intratumoral drug delivery have the dual benefit of reducing systemic toxicity while enhancing efficacy for malignant cells. We have developed a new implantable system combining a next-generation BioNEMS nanofluidic membrane with parallel nanochannels that offers controlled release of biomolecules. Based on concentration-driven diffusive transport, nanochannel membranes provide a {"}drug agnostic{"} delivery mechanism. Integrating this nanotechnology within a small implantable capsule permits multipurpose functionality and compatibility with different therapeutic approaches as well as diagnostic imaging capability. A minimally-invasive, percutaneous trocar delivery mechanism enables serial implantation throughout a target tissue volume. In this manuscript, we demonstrate that this platform is capable of sustained delivery for chemotherapy, radiosensitization, immunomodulation, and imaging contrast, among others. This platform's utility was established through release of doxorubicin, OX86, FGK45, and Magnevist. Further proof-of-concept experiments demonstrated successful in vivo implantation and intratumoral release of antibodies and contrast agents, as well as the platform's MR-compatibility and capability as a radiopaque fiducial. These results provide strong evidence for a flexible, multifunctional nanofluidic implant capable of broadening local delivery utility in the clinic.",
keywords = "BioNEMS Device, Controlled Delivery, Fiducial Marker, Imaging Contrast, Intratumoral Release, Localized Drug Delivery, Nanoconstrained Diffusion, Nanofluidics, Nanotechnology., Radiosensitization",
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journal = "Journal of Biomedical Nanotechnology",
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RIS

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T1 - Nanochannel implants for minimally-invasive insertion and intratumoral delivery

AU - Hood, R. Lyle

AU - Bruno, Giacomo

AU - Jain, Priya

AU - Anderson, Jeff

AU - Wolfe, Tatiana

AU - Quini, Caio

AU - Schmulen, Jeffery

AU - Li, Xian C.

AU - Butler, E. Brian

AU - Krishnan, Sunil

AU - Grattoni, Alessandro

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Novel approaches to achieve local, intratumoral drug delivery have the dual benefit of reducing systemic toxicity while enhancing efficacy for malignant cells. We have developed a new implantable system combining a next-generation BioNEMS nanofluidic membrane with parallel nanochannels that offers controlled release of biomolecules. Based on concentration-driven diffusive transport, nanochannel membranes provide a "drug agnostic" delivery mechanism. Integrating this nanotechnology within a small implantable capsule permits multipurpose functionality and compatibility with different therapeutic approaches as well as diagnostic imaging capability. A minimally-invasive, percutaneous trocar delivery mechanism enables serial implantation throughout a target tissue volume. In this manuscript, we demonstrate that this platform is capable of sustained delivery for chemotherapy, radiosensitization, immunomodulation, and imaging contrast, among others. This platform's utility was established through release of doxorubicin, OX86, FGK45, and Magnevist. Further proof-of-concept experiments demonstrated successful in vivo implantation and intratumoral release of antibodies and contrast agents, as well as the platform's MR-compatibility and capability as a radiopaque fiducial. These results provide strong evidence for a flexible, multifunctional nanofluidic implant capable of broadening local delivery utility in the clinic.

AB - Novel approaches to achieve local, intratumoral drug delivery have the dual benefit of reducing systemic toxicity while enhancing efficacy for malignant cells. We have developed a new implantable system combining a next-generation BioNEMS nanofluidic membrane with parallel nanochannels that offers controlled release of biomolecules. Based on concentration-driven diffusive transport, nanochannel membranes provide a "drug agnostic" delivery mechanism. Integrating this nanotechnology within a small implantable capsule permits multipurpose functionality and compatibility with different therapeutic approaches as well as diagnostic imaging capability. A minimally-invasive, percutaneous trocar delivery mechanism enables serial implantation throughout a target tissue volume. In this manuscript, we demonstrate that this platform is capable of sustained delivery for chemotherapy, radiosensitization, immunomodulation, and imaging contrast, among others. This platform's utility was established through release of doxorubicin, OX86, FGK45, and Magnevist. Further proof-of-concept experiments demonstrated successful in vivo implantation and intratumoral release of antibodies and contrast agents, as well as the platform's MR-compatibility and capability as a radiopaque fiducial. These results provide strong evidence for a flexible, multifunctional nanofluidic implant capable of broadening local delivery utility in the clinic.

KW - BioNEMS Device

KW - Controlled Delivery

KW - Fiducial Marker

KW - Imaging Contrast

KW - Intratumoral Release

KW - Localized Drug Delivery

KW - Nanoconstrained Diffusion

KW - Nanofluidics

KW - Nanotechnology.

KW - Radiosensitization

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