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Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size.

Publication ,  Journal Article
Kong, G; Braun, RD; Dewhirst, MW
Published in: Cancer Res
August 15, 2000

The efficacy of novel cancer therapeutics has been hampered by the ability to deliver these agents to the tumor at effective concentrations. Liposomes have been used as a method to overcome some delivery issues and, in combination with hyperthermia, have been shown to increase drug delivery to tumors. Particle size has been shown to affect the delivery of liposomes, but it is not known how hyperthermia affects size dependence. This study investigates the effect of hyperthermia (42 degrees C) on the extravasation of different sized nanoparticles (albumin; 100-, 200-, and 400-nm liposomes) from tumor microvasculature in a human tumor (SKOV-3 ovarian carcinoma) xenograft grown in mouse window chambers. In this model (at 34 degrees C), no liposomes were able to extravasate into the tumor interstitium. Hyperthermia enabled liposome extravasation of all sizes. The magnitude of hyperthermia-induced extravasation was inversely proportional to particle size. Thus, at normothermia (34 degrees C), the pore cutoff size for this model was between 7 and 100 nm (e.g., liposomes did not extravasate). At 42 degrees C, the pore cutoff size was increased to >400 nm, allowing all nanoparticles tested to be delivered to the tumor interstitium to some degree. With hyperthermia, the 100-nm liposome experienced the largest relative increase in extravasation from tumor vasculature. Hyperthermia did not enable extravasation of 100-nm liposomes from normal vasculature, potentially allowing for tumor-specific delivery. These experiments indicate that hyperthermia can enable and augment liposomal drug delivery to tumors and potentially help target liposomes specifically to tumors.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

August 15, 2000

Volume

60

Issue

16

Start / End Page

4440 / 4445

Location

United States

Related Subject Headings

  • Particle Size
  • Ovarian Neoplasms
  • Organ Specificity
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice
  • Liposomes
  • Injections, Intravenous
  • Hyperthermia, Induced
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kong, G., Braun, R. D., & Dewhirst, M. W. (2000). Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size. Cancer Res, 60(16), 4440–4445.
Kong, G., R. D. Braun, and M. W. Dewhirst. “Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size.Cancer Res 60, no. 16 (August 15, 2000): 4440–45.
Kong G, Braun RD, Dewhirst MW. Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size. Cancer Res. 2000 Aug 15;60(16):4440–5.
Kong, G., et al. “Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size.Cancer Res, vol. 60, no. 16, Aug. 2000, pp. 4440–45.
Kong G, Braun RD, Dewhirst MW. Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size. Cancer Res. 2000 Aug 15;60(16):4440–4445.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

August 15, 2000

Volume

60

Issue

16

Start / End Page

4440 / 4445

Location

United States

Related Subject Headings

  • Particle Size
  • Ovarian Neoplasms
  • Organ Specificity
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice
  • Liposomes
  • Injections, Intravenous
  • Hyperthermia, Induced