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. 2011;6(9):e24374.
doi: 10.1371/journal.pone.0024374. Epub 2011 Sep 13.

Modulating pharmacokinetics, tumor uptake and biodistribution by engineered nanoparticles

Rochelle R Arvizo  1 , Oscar R Miranda, Daniel F Moyano, Chad A Walden, Karuna Giri, Resham Bhattacharya, J David Robertson, Vincent M Rotello, Joel M Reid, Priyabrata Mukherjee
Affiliations

Modulating pharmacokinetics, tumor uptake and biodistribution by engineered nanoparticles

Rochelle R Arvizo et al. PLoS One. 2011.

Abstract

Background: Inorganic nanoparticles provide promising tools for biomedical applications including detection, diagnosis and therapy. While surface properties such as charge are expected to play an important role in their in vivo behavior, very little is known how the surface chemistry of nanoparticles influences their pharmacokinetics, tumor uptake, and biodistribution.

Method/principal findings: Using a family of structurally homologous nanoparticles we have investigated how pharmacological properties including tumor uptake and biodistribution are influenced by surface charge using neutral (TEGOH), zwitterionic (Tzwit), negative (TCOOH) and positive (TTMA) nanoparticles. Nanoparticles were injected into mice (normal and athymic) either in the tail vein or into the peritoneum.

Conclusion: Neutral and zwitterionic nanoparticles demonstrated longer circulation time via both i.p. and i.v. administration, whereas negatively and positively charged nanoparticles possessed relatively short half-lives. These pharmacological characteristics were reflected on the tumor uptake and biodistribution of the respective nanoparticles, with enhanced tumor uptake by neutral and zwitterionic nanoparticles via passive targeting.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Structural representation of gold nanoparticles (2 nm core diameter) used.
Gold nanoparticles (AuNPs) of different surface charges were generated by chemical modification of the terminal portion of the ligand bonded to the nanoparticle core. Four types of AuNPs were used neutral (TEGOH), positive (TTMA), negative (TCOOH) and zwitterionic (TZwit). The surface charge was measured by zeta potential.
Figure 2
Figure 2. Plasma profiles for gold nanoparticles.
Normal mice were injected either (A) intravenously or (B) intraperitoneally. Data points are the mean +/− SEM from n = 3 animals.
Figure 3
Figure 3. Quantification of in vivo accumulation of gold nanoparticles into tumors.
Coinciding with the blood concentration, nanoparticles that showed a long retention time in circulation were able to extravasate and accumulate into the tumor. Data points are the mean +/− SEM from n = 5 animals.
Figure 4
Figure 4. Tissue distribution of gold nanoparticles in mice.
In vivo mean gold concentration (µg) per gram of organ 24 hours post (A) IP injection and (B) IV injection. The mode of administration and the ligand end group of AuNPs affects the level of gold uptake in different tissues with the RES being the dominant mode of clearance. Data points are the mean +/− SEM from n = 5 animals. Results are reported as gold concentration (µg) per gram of organ.
See this image and copyright information in PMC

References

    1. Petros RA, DeSimone JM. Strategies in the design of nanoparticles for therapeutic applications. Nature Review Drug Discovery. 2010;9(8):615–627. - PubMed
    1. Davis AJ, Tannock IF. Tumor physiology and resistance to chemotherapy: repopulation and drug penetration. Cancer Treat Res. 2002;112:1–26. - PubMed
    1. Gindy ME, Prud'homme RK. Multifunctional nanoparticles for imaging, delivery and targeting in cancer therapy. Expert Opinion on Drug Delivery. 2009;6(8):865–878. - PubMed
    1. Gao J, Liang G, Zhang B, Kuang Y, Zhang X, et al. FePt@CoS(2) yolk-shell nanocrystals as a potent agent to kill HeLa cells. J Am Chem Soc. 2007;129(5):1428–1433. - PubMed
    1. Langer R, Tirrell DA. Designing materials for biology and medicine. Nature. 2004;428(6982):487–492. - PubMed

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