PuSH - Publikationsserver des Helmholtz Zentrums München

Manzoor, A.A.* ; Lindner, L.H. ; Landon, C.D.* ; Park, J.Y.* ; Simnick, A.J.* ; Dreher, M.R.* ; Das, S.* ; Hanna, G.* ; Park, W.* ; Chilkoti, A.* ; Koning, G.A.* ; ten Hagen, T.L.M.* ; Needham, D.* ; Dewhirst, M.W.*

Overcoming limitations in nanoparticle drug delivery: Triggered, intravascular release to improve drug penetration into tumors.

Cancer Res. 72, 5566-5575 (2012)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Traditionally, the goal of nanoparticle-based chemotherapy has been to decrease normal tissue toxicity by improving drug specificity to tumors. The enhanced permeability and retention effect can permit passive accumulation into tumor interstitium. However, suboptimal delivery is achieved with most nanoparticles because of heterogeneities of vascular permeability, which limits nanoparticle penetration. Furthermore, slow drug release limits bioavailability. We developed a fast drug-releasing liposome triggered by local heat that has already shown substantial antitumor efficacy and is in human trials. Here, we show that thermally sensitive liposomes (Dox-TSL) release doxorubicin inside the tumor vasculature. Real-time confocal imaging of doxorubicin delivery to murine tumors in window chambers and histologic analysis of flank tumors illustrates that intravascular drug release increases free drug in the interstitial space. This increases both the time that tumor cells are exposed to maximum drug levels and the drug penetration distance, compared with free drug or traditional pegylated liposomes. These improvements in drug bioavailability establish a new paradigm in drug delivery: rapidly triggered drug release in the tumor bloodstream. Cancer Res; 72(21); 5566-75. (C)2012 AACR.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Temperature-sensitive Liposomes ; Solid Tumors ; Thermosensitive Liposomes ; Local Hyperthermia ; Selective Delivery ; Mild Hyperthermia ; Xenograft Model ; Blood-vessels ; Murine Tumors ; In-vitro
ISSN (print) / ISBN 0008-5472
e-ISSN 1538-7445
Zeitschrift Cancer Research
Quellenangaben Band: 72, Heft: 21, Seiten: 5566-5575 Artikelnummer: , Supplement: ,
Verlag American Association for Cancer Research (AACR)
Verlagsort Philadelphia, Pa.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CCG Tumor Therapy with Hyperthermia (IMI-KTH)