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Adv Mater. 2018 Dec;30(50):e1805557. doi: 10.1002/adma.201805557. Epub 2018 Oct 11.

Nanoparticle-Laden Macrophages for Tumor-Tropic Drug Delivery.

Author information

1
Department of Chemistry, University of Georgia, Athens, GA, 30602, USA.
2
Department of Radiology and Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
3
Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.
4
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia Athens, Athens, GA, 30602, USA.

Abstract

Macrophages hold great potential in cancer drug delivery because they can sense chemotactic cues and home to tumors with high efficiency. However, it remains a challenge to load large amounts of therapeutics into macrophages without compromising cell functions. This study reports a silica-based drug nanocapsule approach to solve this issue. The nanocapsule consists of a drug-silica complex filling and a solid silica sheath, and it is designed to minimally release drug molecules in the early hours of cell entry. While taken up by macrophages at high rates, the nanocapsules minimally affect cell migration in the first 6-12 h, buying time for macrophages to home to tumors and release drugs in situ. In particular, it is shown that doxorubicin (Dox) as a representative drug can be loaded into macrophages up to 16.6 pg per cell using this approach. When tested in a U87MG xenograft model, intravenously (i.v.) injected Dox-laden macrophages show comparable tumor accumulation as untreated macrophages. Therapy leads to efficient tumor growth suppression, while causing little systematic toxicity. This study suggests a new cell platform for selective drug delivery, which can be readily extended to the treatment of other types of diseases.

KEYWORDS:

cancer; cell-mediated drug delivery; doxorubicin; glioblastoma; macrophages; nanoparticles

PMID:
30368972
PMCID:
PMC6506271
DOI:
10.1002/adma.201805557
[Indexed for MEDLINE]
Free PMC Article

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