Format

Send to

Choose Destination
J Control Release. 2014 Oct 10;191:115-22. doi: 10.1016/j.jconrel.2014.05.006. Epub 2014 May 14.

Prolonged blood circulation and enhanced tumor accumulation of folate-targeted dendrimer-polymer hybrid nanoparticles.

Author information

1
Department of Biopharmaceutical Sciences, University of Illinois, Chicago 60612, USA.
2
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago 60612, USA.
3
Department of Biopharmaceutical Sciences, University of Illinois, Chicago 60612, USA; Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago 60612, USA.
4
Department of Biopharmaceutical Sciences, University of Illinois, Chicago 60612, USA; Department of Biongineering, University of Illinois, Chicago 60612, USA. Electronic address: sphong@uic.edu.

Abstract

Nanoparticle (NP)-based drug delivery platforms have received a great deal of attention over the past two decades for their potential in targeted cancer therapies. Despite the promises, passive targeting approaches utilizing relatively larger NPs (typically 50-200nm in diameter) allow for passive tumor accumulation, but hinder efficient intratumoral penetration. Conversely, smaller, actively targeted NPs (<20nm in diameter) penetrate well into the tumor mass, but are limited by their rapid systemic elimination. To overcome these limitations, we have designed a multi-scale hybrid NP platform that loads smaller poly(amidoamine) (PAMAM) dendrimers (~5nm in diameter) into larger poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PLA) NPs (~70nm). A biodistribution study in healthy mice revealed that the hybrid NPs circulated longer than free dendrimers and were mostly cleared by macrophages in the liver and spleen, similar to the in vivo behavior of PEG-PLA NPs. When injected intravenously into the BALB/c athymic nude mice bearing folate receptor (FR)-overexpressing KB xenograft, the targeted hybrid NPs encapsulating folate (FA)-targeted dendrimers achieved longer plasma circulation than free dendrimers and higher tumor concentrations than both free dendrimers and the empty PEG-PLA NPs. These results suggest that the hybrid NPs successfully combine the in vivo advantages of dendrimers and polymeric NPs, demonstrating their potential as a new, modular platform for drug delivery.

KEYWORDS:

Dendrimer; In vivo targeting; Nanoparticle

PMID:
24837188
PMCID:
PMC4156894
DOI:
10.1016/j.jconrel.2014.05.006
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center