The passive targeting of polymeric micelles in various types and sizes of tumor models

Kai Xiao, Juntao Luo, Yuanpei Li, Wenwu Xiao, Joyce S Lee, Abby M. Gonik, Kit Lam

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Nanoparticles with 10-100 nm in diameter could selectively accumulate in tumor tissue via the enhanced permeability and retention (EPR) effect. This "passive targeting" is believed to be the result of the defective "leaky" vasculature and reduced lymphatic drainage systems in most solid tumors. The physicochemical characteristics of nanoparticles such as particle size and surface charge can dramatically affect the EPR effect and tumor targeting property. The EPR effect and anti-cancer efficacy of nanoparticles may also be influenced by the variation of tumor characteristics including cancer type, stage of disease, site of implantation and host species. We have developed a novel linear dendritic block copolymer, composed of polyethylene glycol (PEG) and dendritic oligomer of cholic acid, which self-assembles into nano-sized stable micelles for targeting delivery of anticancer drug in ovarian cancer xenograft models. In this study, we used near infrared fluorescence (NIRF) optical imaging technique to systematically investigate the in vivo passive accumulation of this newly developed polymeric micelle (via EPR effect) in different types and sizes of tumors. The results demonstrated that the micelles could preferentially accumulate in many types of tumor xenografts or synografts implanted in mice. Nanoparticle uptake in solid tumors was found to be much higher than that of lymphoma, which could be attributed to the relatively low microvascular density in the latter. Furthermore, the passive tumor targeting of micelles was investigated in the transgenic mammary carcinoma mouse model, indicating micelles could accumulate in the tumors to varying extent, with higher uptake in medium (5-7 mm) and large (8-10 mm) tumors than that in small tumors (2-4 mm), which is likely due to the lack of or underdeveloped vasculature network in small tumors.

Original languageEnglish (US)
Pages (from-to)79-85
Number of pages7
JournalNanoscience and Nanotechnology Letters
Volume2
Issue number2
DOIs
StatePublished - Jun 2010

Keywords

  • Enhanced Permeability and Retention (EPR) Effect
  • Micelle
  • Near Infrared Fluorescence (NIRF)
  • Optical Imaging
  • Polymeric Nanoparticle
  • Tumor Size
  • Tumor Type

ASJC Scopus subject areas

  • Materials Science(all)

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