Journal article
Indocarbocyanine nanoparticles extravasate and distribute better than liposomes in brain tumors
Journal of controlled release, Vol.349, pp.413-424
09/2022
DOI: 10.1016/j.jconrel.2022.07.008
PMCID: PMC10200250
PMID: 35817279
Abstract
Glioblastoma (GBM) is the most devastating and aggressive brain tumor in adults. Hidden behind the blood-brain and blood-tumor barriers (BBTB), this invasive type of brain tumor is not readily accessible to nano-sized particles. Here we demonstrate that fluorescent indocarbocyanine lipids (ICLs: DiD, DiI) formulated in PEGylated lipid nanoparticle (PLN) exhibit highly efficient penetration and accumulation in GBM. PLN-formulated ICLs demonstrated more efficient penetration in GBM spheroids and organoids in vitro than liposomal ICLs. Over 82% of the tumor's extravascular area was positive for ICL fluorescence in the PLN group versus 13% in the liposomal group just one hour post-systemic injection in the intracranial GBM model. Forty-eight hours post-injection, PLN-formulated ICLs accumulated in 95% of tumor myeloid-derived suppressor cells and macrophages, 70% of tumor regulatory T cells, 50% of tumor-associated microglia, and 65% of non-immune cells. PLN-formulated ICLs extravasated better than PEGylated liposomal doxorubicin and fluorescent dextran and efficiently accumulated in invasive tumor margins and brain-invading cells. While liposomes were stable in serum in vitro and in vivo, PLNs disassembled before entering tumors, which could explain the differences in their extravasation efficiency. These findings offer an opportunity to improve therapeutic cargo delivery to invasive GBM.
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Details
- Title: Subtitle
- Indocarbocyanine nanoparticles extravasate and distribute better than liposomes in brain tumors
- Creators
- Irina V. Balyasnikova - Northwestern UniversityMarkella Zannikou - Northwestern UniversityGuankui Wang - University of MontanaYue Li - University of MontanaJoseph T. Duffy - Northwestern UniversityRebecca N. Levine - Northwestern UniversityMaggie Seblani - Northwestern UniversityHanmant Gaikwad - University of MontanaDmitri Simberg - University of Montana
- Resource Type
- Journal article
- Publication Details
- Journal of controlled release, Vol.349, pp.413-424
- DOI
- 10.1016/j.jconrel.2022.07.008
- PMID
- 35817279
- PMCID
- PMC10200250
- NLM abbreviation
- J Control Release
- ISSN
- 0168-3659
- eISSN
- 1873-4995
- Publisher
- Elsevier B.V
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01CA257958-01A1, R01NS106379, R01NS122395
- Language
- English
- Date published
- 09/2022
- Academic Unit
- Stead Family Department of Pediatrics
- Record Identifier
- 9984353843402771
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