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Jai Woong Seo1, JooChuan Ang2, Lisa M Mahakian1
1Department of Biomedical Engineering, University of California, Davis, Davis, CA, United States.
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 16.5h, 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/cm(3) for the micelles and 0.45%ID/cm(3) for the liposomes. For GBM lesions with a volume greater than 100mm(3), 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.
Insights
Smaller nanocarriers, specifically 20-nm three-helix micelles (3HM), show enhanced accumulation in glioblastoma multiforme (GBM) tumors compared to larger liposomes. These 3HM nanocarriers effectively deliver treatment to GBM lesions and surrounding tissue.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Glioblastoma multiforme (GBM) treatment requires effective nanocarrier drug delivery systems.
- Current nanocarriers face challenges in tumor accumulation and distribution.
- There is a need for optimized nanocarrier designs for GBM therapy.
Purpose of the Study:
- To investigate the impact of nanocarrier size on glioblastoma multiforme (GBM) pharmacokinetics and biodistribution.
- To evaluate 20-nm three-helix micelles (3HM) as a potential nanocarrier for GBM treatment.
- To compare the tumor accumulation of 3HM with larger nanocarriers.
Main Methods:
- Utilized co-registered positron emission tomography (PET) and magnetic resonance (MR) imaging in rodent GBM xenograft models.
- Systematically studied the pharmacokinetics and biodistribution of 20-nm 3HM and 110-nm PEGylated liposomes.
- Quantified nanoparticle extravasation and accumulation within tumors using PET imaging.
Main Results:
- 3HM exhibited similar circulation half-life to PEGylated liposomes but significantly enhanced accumulation in U87MG xenografts.
- Quantified extravasated nanoparticles showed higher concentration for 3HM (~0.77%ID/cm³) compared to liposomes (~0.45%ID/cm³).
- 3HM accumulation was observed within detectable GBM tumors, surrounding brain parenchyma, and at tumor margins.
Conclusions:
- 20-nm three-helix micelles (3HM) demonstrate superior tumor accumulation and distribution for glioblastoma multiforme (GBM) compared to larger nanocarriers.
- 3HM represent a promising nanovehicle for targeted drug delivery in GBM treatment.
- Nanocarrier size is a critical factor influencing therapeutic efficacy in GBM.
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