Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

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

Publication ,  Journal Article
Manzoor, AA; Lindner, LH; Landon, CD; Park, J-Y; Simnick, AJ; Dreher, MR; Das, S; Hanna, G; Park, W; Chilkoti, A; Koning, GA; ten Hagen, TLM ...
Published in: Cancer Res
November 1, 2012

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

November 1, 2012

Volume

72

Issue

21

Start / End Page

5566 / 5575

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Oncology & Carcinogenesis
  • Neoplasms, Experimental
  • Nanoparticles
  • Microscopy, Confocal
  • Mice
  • Liposomes
  • Humans
  • Hot Temperature
  • Drug Delivery Systems
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Manzoor, A. A., Lindner, L. H., Landon, C. D., Park, J.-Y., Simnick, A. J., Dreher, M. R., … Dewhirst, M. W. (2012). Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors. Cancer Res, 72(21), 5566–5575. https://doi.org/10.1158/0008-5472.CAN-12-1683
Manzoor, Ashley A., Lars H. Lindner, Chelsea D. Landon, Ji-Young Park, Andrew J. Simnick, Matthew R. Dreher, Shiva Das, et al. “Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors.Cancer Res 72, no. 21 (November 1, 2012): 5566–75. https://doi.org/10.1158/0008-5472.CAN-12-1683.
Manzoor AA, Lindner LH, Landon CD, Park J-Y, Simnick AJ, Dreher MR, et al. Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors. Cancer Res. 2012 Nov 1;72(21):5566–75.
Manzoor, Ashley A., et al. “Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors.Cancer Res, vol. 72, no. 21, Nov. 2012, pp. 5566–75. Pubmed, doi:10.1158/0008-5472.CAN-12-1683.
Manzoor AA, Lindner LH, Landon CD, Park J-Y, Simnick AJ, Dreher MR, Das S, Hanna G, Park W, Chilkoti A, Koning GA, ten Hagen TLM, Needham D, Dewhirst MW. Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors. Cancer Res. 2012 Nov 1;72(21):5566–5575.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

November 1, 2012

Volume

72

Issue

21

Start / End Page

5566 / 5575

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Oncology & Carcinogenesis
  • Neoplasms, Experimental
  • Nanoparticles
  • Microscopy, Confocal
  • Mice
  • Liposomes
  • Humans
  • Hot Temperature
  • Drug Delivery Systems