Abstract
There is an urgent need to develop nanocarriers for the treatment of glioblastoma multiforme (GBM). Using co-registered positron emission tomography (PET) and magnetic resonance (MR) images, here we performed systematic studies to investigate how a nanocarrier's size affects the pharmacokinetics and biodistribution in rodents with a GBM xenograft. In particular, highly stable, long-circulating three-helix micelles (3HM), based on a coiled-coil protein tertiary structure, were evaluated as an alternative to larger nanocarriers. While the circulation half-life of the 3HM was similar to 110-nm PEGylated liposomes (t1/2 = 15.5 and 16.5 h, respectively), the 20-nm micelles greatly enhanced accumulation within a U87MG xenograft in nu/nu rats after intravenous injection. After accounting for tumor blood volume, the extravasated nanoparticles were quantified from the PET images, yielding ~ 0.77%ID/cm3 for the micelles and 0.45%ID/cm3 for the liposomes. For GBM lesions with a volume greater than 100 mm3, 3HM accumulation was enhanced both within the detectable tumor and in the surrounding brain parenchyma. Further, the nanoparticle accumulation was shown to extend to the margins of the GBM xenograft. In summary, 3HM provides an attractive nanovehicle for carrying treatment to GBM.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 51-60 |
| Number of pages | 10 |
| Journal | Journal of Controlled Release |
| Volume | 220 |
| DOIs | |
| State | Published - Dec 28 2015 |
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Keywords
- BBB
- Blood brain barrier
- Drug delivery
- Glioblastoma
- Liposome
- Micelles
- Nanoparticle
- PET
- PET/MR
- Positron emission tomography
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Self-assembled 20-nm 64Cu-micelles enhance accumulation in rat glioblastoma. / Seo, Jai; Ang, JooChuan; Mahakian, Lisa M.; Tam, Sarah; Fite, Brett; Ingham, Elizabeth S.; Beyer, Janine; Forsayeth, John; Bankiewicz, Krystof S.; Xu, Ting; Ferrara, Katherine W.
In: Journal of Controlled Release, Vol. 220, 28.12.2015, p. 51-60.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Self-assembled 20-nm 64Cu-micelles enhance accumulation in rat glioblastoma
AU - Seo, Jai
AU - Ang, JooChuan
AU - Mahakian, Lisa M.
AU - Tam, Sarah
AU - Fite, Brett
AU - Ingham, Elizabeth S.
AU - Beyer, Janine
AU - Forsayeth, John
AU - Bankiewicz, Krystof S.
AU - Xu, Ting
AU - Ferrara, Katherine W.
PY - 2015/12/28
Y1 - 2015/12/28
N2 - There is an urgent need to develop nanocarriers for the treatment of glioblastoma multiforme (GBM). Using co-registered positron emission tomography (PET) and magnetic resonance (MR) images, here we performed systematic studies to investigate how a nanocarrier's size affects the pharmacokinetics and biodistribution in rodents with a GBM xenograft. In particular, highly stable, long-circulating three-helix micelles (3HM), based on a coiled-coil protein tertiary structure, were evaluated as an alternative to larger nanocarriers. While the circulation half-life of the 3HM was similar to 110-nm PEGylated liposomes (t1/2 = 15.5 and 16.5 h, respectively), the 20-nm micelles greatly enhanced accumulation within a U87MG xenograft in nu/nu rats after intravenous injection. After accounting for tumor blood volume, the extravasated nanoparticles were quantified from the PET images, yielding ~ 0.77%ID/cm3 for the micelles and 0.45%ID/cm3 for the liposomes. For GBM lesions with a volume greater than 100 mm3, 3HM accumulation was enhanced both within the detectable tumor and in the surrounding brain parenchyma. Further, the nanoparticle accumulation was shown to extend to the margins of the GBM xenograft. In summary, 3HM provides an attractive nanovehicle for carrying treatment to GBM.
AB - There is an urgent need to develop nanocarriers for the treatment of glioblastoma multiforme (GBM). Using co-registered positron emission tomography (PET) and magnetic resonance (MR) images, here we performed systematic studies to investigate how a nanocarrier's size affects the pharmacokinetics and biodistribution in rodents with a GBM xenograft. In particular, highly stable, long-circulating three-helix micelles (3HM), based on a coiled-coil protein tertiary structure, were evaluated as an alternative to larger nanocarriers. While the circulation half-life of the 3HM was similar to 110-nm PEGylated liposomes (t1/2 = 15.5 and 16.5 h, respectively), the 20-nm micelles greatly enhanced accumulation within a U87MG xenograft in nu/nu rats after intravenous injection. After accounting for tumor blood volume, the extravasated nanoparticles were quantified from the PET images, yielding ~ 0.77%ID/cm3 for the micelles and 0.45%ID/cm3 for the liposomes. For GBM lesions with a volume greater than 100 mm3, 3HM accumulation was enhanced both within the detectable tumor and in the surrounding brain parenchyma. Further, the nanoparticle accumulation was shown to extend to the margins of the GBM xenograft. In summary, 3HM provides an attractive nanovehicle for carrying treatment to GBM.
KW - BBB
KW - Blood brain barrier
KW - Drug delivery
KW - Glioblastoma
KW - Liposome
KW - Micelles
KW - Nanoparticle
KW - PET
KW - PET/MR
KW - Positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=84944719510&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84944719510&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2015.09.057
DO - 10.1016/j.jconrel.2015.09.057
M3 - Article
C2 - 26437259
AN - SCOPUS:84944719510
VL - 220
SP - 51
EP - 60
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -