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Review
. 2011 Jun 15;22(6):993-1000.
doi: 10.1021/bc200111p. Epub 2011 May 11.

Biologically optimized nanosized molecules and particles: more than just size

Michelle R Longmire  1 , Mikako Ogawa, Peter L Choyke, Hisataka Kobayashi
Affiliations
Review

Biologically optimized nanosized molecules and particles: more than just size

Michelle R Longmire et al. Bioconjug Chem. .

Abstract

The expanded biological and medical applications of nanomaterials place a premium on better understanding of the chemical and physical determinants of in vivo particles. Nanotechnology allows us to design a vast array of molecules with distinct chemical and biological characteristics, each with a specific size, charge, hydrophilicity, shape, and flexibility. To date, much research has focused on the role of particle size as a determinant of biodistribution and clearance. Additionally, much of what we know about the relationship between nanoparticle traits and pharmacokinetics has involved research limited to the gross average hydrodynamic size. Yet, other features such as particle shape and flexibility affect in vivo behavior and become increasingly important for designing and synthesizing nanosized molecules. Herein, we discuss determinants of in vivo behavior of nanosized molecules used as imaging agents with a focus on dendrimer-based contrast agents. We aim to discuss often overlooked or, yet to be considered, factors that affect in vivo behavior of synthetic nanosized molecules, as well as aim to highlight important gaps in current understanding.

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Figures

Figure 1
Figure 1
Two long linear PEG (20kD) conjugated PAMAM-G4-Gd shows renal excretion. However, Short PEG (2kD) conjugated PAMAM-G4-Gd of similar physical size shows no renal excretion.
Figure 2
Figure 2
Despite of small size, hard interior (high density) EDA-core PAMAM-G6 does not show renal excretion. Two other “softer” interior dendrimers show renal excretion.
Figure 3
Figure 3
Strategic use of dendrimer size to achieve organ-specific imaging. This schema depits a generation 3 dendrimer, with core chemistry, shape, and surface modifications functionalized for use as an MRI contrast agent. Images of mice demonstrate that stragtegic selection of dendrimer size enables target organ-specific imaging. For example, PAMAM-G8 shows the lymphatic system; PAMAM-G6 shows the blood pool; PAMAM-G4 depicts renal function; and PPI/DAM-G4 depicts liver parenchyma.
Figure 4
Figure 4
A schema for glomerular filtration of hard and soft nano-sized molecules or particles.
See this image and copyright information in PMC

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