Modulating Pharmacokinetics, Tumor Uptake and Biodistribution by Engineered Nanoparticles

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Sep 21

PMID 21931696

Citations 155

Authors

Rochelle R Arvizo

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

Soon will be listed here.

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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References

Peer D, Karp J, Hong S, Farokhzad O, Margalit R, Langer R . Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2008; 2(12):751-60. DOI: 10.1038/nnano.2007.387. View

Fang J, Nakamura H, Maeda H . The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev. 2010; 63(3):136-51. DOI: 10.1016/j.addr.2010.04.009. View

Owens 3rd D, Peppas N . Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2005; 307(1):93-102. DOI: 10.1016/j.ijpharm.2005.10.010. View

Simberg D, Park J, Karmali P, Zhang W, Merkulov S, McCrae K . Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance. Biomaterials. 2009; 30(23-24):3926-33. PMC: 2792080. DOI: 10.1016/j.biomaterials.2009.03.056. View

Sinha R, Kim G, Nie S, Shin D . Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery. Mol Cancer Ther. 2006; 5(8):1909-17. DOI: 10.1158/1535-7163.MCT-06-0141. View

Li M, Al-Jamal K, Kostarelos K, Reineke J . Physiologically based pharmacokinetic modeling of nanoparticles. ACS Nano. 2010; 4(11):6303-17. DOI: 10.1021/nn1018818. View

Langer R, Tirrell D . Designing materials for biology and medicine. Nature. 2004; 428(6982):487-92. DOI: 10.1038/nature02388. View

Ferrari M . Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer. 2005; 5(3):161-71. DOI: 10.1038/nrc1566. View

Jain R, Stylianopoulos T . Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol. 2010; 7(11):653-64. PMC: 3065247. DOI: 10.1038/nrclinonc.2010.139. View

10.

Arvizo R, Miranda O, Thompson M, Pabelick C, Bhattacharya R, Robertson J . Effect of nanoparticle surface charge at the plasma membrane and beyond. Nano Lett. 2010; 10(7):2543-8. PMC: 2925219. DOI: 10.1021/nl101140t. View

11.

Medintz I, Uyeda H, Goldman E, Mattoussi H . Quantum dot bioconjugates for imaging, labelling and sensing. Nat Mater. 2005; 4(6):435-46. DOI: 10.1038/nmat1390. View

12.

Kanaras A, Kamounah F, Schaumburg K, Kiely C, Brust M . Thioalkylated tetraethylene glycol: a new ligand for water soluble monolayer protected gold clusters. Chem Commun (Camb). 2002; (20):2294-5. DOI: 10.1039/b207838b. View

13.

Agasti S, Chompoosor A, You C, Ghosh P, Kim C, Rotello V . Photoregulated release of caged anticancer drugs from gold nanoparticles. J Am Chem Soc. 2009; 131(16):5728-9. PMC: 2673701. DOI: 10.1021/ja900591t. View

14.

Gwak H, Choi J, Choi H . Enhanced bioavailability of piroxicam via salt formation with ethanolamines. Int J Pharm. 2005; 297(1-2):156-61. DOI: 10.1016/j.ijpharm.2005.03.016. View

15.

Templeton A, Wuelfing W, Murray R . Monolayer-protected cluster molecules. Acc Chem Res. 2000; 33(1):27-36. DOI: 10.1021/ar9602664. View

16.

Davis A, Tannock I . Tumor physiology and resistance to chemotherapy: repopulation and drug penetration. Cancer Treat Res. 2002; 112:1-26. DOI: 10.1007/978-1-4615-1173-1_1. View

17.

Schluep T, Hwang J, Hildebrandt I, Czernin J, Choi C, Alabi C . Pharmacokinetics and tumor dynamics of the nanoparticle IT-101 from PET imaging and tumor histological measurements. Proc Natl Acad Sci U S A. 2009; 106(27):11394-9. PMC: 2703672. DOI: 10.1073/pnas.0905487106. View

18.

Chanda N, Kan P, Watkinson L, Shukla R, Zambre A, Carmack T . Radioactive gold nanoparticles in cancer therapy: therapeutic efficacy studies of GA-198AuNP nanoconstruct in prostate tumor-bearing mice. Nanomedicine. 2009; 6(2):201-9. DOI: 10.1016/j.nano.2009.11.001. View

19.

Grobmyer S, Iwakuma N, Sharma P, Moudgil B . What is cancer nanotechnology?. Methods Mol Biol. 2010; 624:1-9. DOI: 10.1007/978-1-60761-609-2_1. View

20.

Wu W, Wieckowski S, Pastorin G, Benincasa M, Klumpp C, Briand J . Targeted delivery of amphotericin B to cells by using functionalized carbon nanotubes. Angew Chem Int Ed Engl. 2005; 44(39):6358-62. DOI: 10.1002/anie.200501613. View