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Dose‐Dependent Therapeutic Distinction between Active and Passive Targeting Revealed Using Transferrin‐Coated PGMA Nanoparticles
Author(s) -
Singh Ruhani,
Norret Marck,
House Michael J.,
Galabura Yuriy,
Bradshaw Michael,
Ho Diwei,
Woodward Robert C.,
Pierre Timothy G. St.,
Luzinov Igor,
Smith Nicole M.,
Lim Lee Yong,
Iyer Killugudi Swaminathan
Publication year - 2016
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201502730
Subject(s) - transferrin , nanoparticle , materials science , nanotechnology , biophysics , chemistry , chemical engineering , biochemistry , biology , engineering
The paradigm of using nanoparticle‐based formulations for drug delivery relies on their enhanced passive accumulation in the tumor interstitium. Nanoparticles with active targeting capabilities attempt to further enhance specific delivery of drugs to the tumors via interaction with overexpressed cellular receptors. Consequently, it is widely accepted that drug delivery using actively targeted nanoparticles maximizes the therapeutic benefit and minimizes the off‐target effects. However, the process of nanoparticle mediated active targeting initially relies on their passive accumulation in tumors. In this article, it is demonstrated that these two tumor‐targeted drug delivery mechanisms are interrelated and dosage dependent. It is reported that at lower doses, actively targeted nanoparticles have distinctly higher efficacy in tumor inhibition than their passively targeted counterparts. However, the enhanced permeability and retention effect of the tumor tissue becomes the dominant factor influencing the efficacy of both passively and actively targeted nanoparticles when they are administered at higher doses. Importantly, it is demonstrated that dosage is a pivotal parameter that needs to be taken into account in the assessment of nanoparticle mediated targeted drug delivery.