Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Oct;64(13):1363-84.
doi: 10.1016/j.addr.2012.08.005. Epub 2012 Aug 17.

Interactions of nanomaterials and biological systems: Implications to personalized nanomedicine

Xue-Qing Zhang  1 , Xiaoyang Xu, Nicolas Bertrand, Eric Pridgen, Archana Swami, Omid C Farokhzad
Affiliations
Review

Interactions of nanomaterials and biological systems: Implications to personalized nanomedicine

Xue-Qing Zhang et al. Adv Drug Deliv Rev. 2012 Oct.

Abstract

The application of nanotechnology to personalized medicine provides an unprecedented opportunity to improve the treatment of many diseases. Nanomaterials offer several advantages as therapeutic and diagnostic tools due to design flexibility, small sizes, large surface-to-volume ratio, and ease of surface modification with multivalent ligands to increase avidity for target molecules. Nanomaterials can be engineered to interact with specific biological components, allowing them to benefit from the insights provided by personalized medicine techniques. To tailor these interactions, a comprehensive knowledge of how nanomaterials interact with biological systems is critical. Herein, we discuss how the interactions of nanomaterials with biological systems can guide their design for diagnostic, imaging and drug delivery purposes. A general overview of nanomaterials under investigation is provided with an emphasis on systems that have reached clinical trials. Finally, considerations for the development of personalized nanomedicines are summarized such as the potential toxicity, scientific and technical challenges in fabricating them, and regulatory and ethical issues raised by the utilization of nanomaterials.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The physicochemical properties of the nanomaterial surface can trigger the different pathways of complement cascade activation [49-55]. The classical pathway is activated through deposition of specific proteins like antibodies and others. The lectin pathway is triggered by the recognition of the surface by a Mannose-binding Lectin (MBL) through pathogen-associated motifs. The lectin subsequently interacts with a serine protease (MASP) to elicit the formation of a C3-convertase (C4b2a) analogously to the classical pathway. The spontaneous tickover responsible for the alternative pathway activation is constantly present in plasma. When not properly regulated, the preferred deposition of the C3b products on the surface of the nanomaterial amplifies the cascade activation. All 3 pathways lead to C5-convertases that cleave C5 and lead to the deposition of the terminal membrane attack complex which can lyse pathogens and senescent cells, further releasing proinflammatory mediators. The release of proinflammatory chemoattractants is symbolized by the yellow outburst.
Figure 2
Figure 2
Mechanisms for the transport and accumulation of albumin-bound paclitaxel in tumors. Binding of albumin-bound paclitaxel complexes to the gp60 receptor and subsequent caveolin-1 mediated transcytosis results in transport across the endothelial barrier of the tumor vasculature. SPARC, an albumin-binding protein present in the tumor interstitium, enhances accumulation of the complexes in tumor tissue. Figure taken from reference [59].
Figure 3
Figure 3
(A) Nanoparticles with ligands specific for endothelial cell surface markers allow for binding and accumulation to tumor vasculature. (B) Once in the tumor tissue, nanoparticles with ligands specific for tumor cell markers can actively bind to tumor cells, enhancing accumulations and promoting receptor-mediated endocytosis. Figure taken from reference [69].
Figure 4
Figure 4
Assembly and function of targeted cyclodextrin nanoparticles containing siRNA. (a) Nanoparticles consist of four components: (i) a water-soluble, linear cyclodextrin-containing polymer (CDP), (ii) an adamantane (AD)-PEG conjugate (AD-PEG), (iii) the targeting component that has human transferrin (Tf) conjugated to AD-PEG (Tf-PEG-AD), and (iv) siRNA. (b) Aqueous nanoparticle solutions are infused into patients and circulate throughout the body. (c) Nanoparticles accumulate in tumor tissue due to the EPR effect. (D and E) Nanoparticle targeting ligands bind to Tf receptors on tumor cells, resulting in endocytosis (transmission electron micrograph of 50 nm nanoparticles entering a cancer cell). Figure taken from reference [79].
Figure 5
Figure 5
(A and B) Two-step process for targeting biomarkers on cancer cells. Live cells are labeled with TCO-modified antibodies followed by covalent reaction with Tz-modified fluorescent0labeled iron oxide nanoparticles. (C) Cell profiling using a miniaturized diagnostic magnetic resonance device. Excellent correlation was observed between NMR signals of tumor cells and marker expression levels measured using flow cytometry. Figure taken from reference [102].
Figure 6
Figure 6
(A) Cell-uptake selection process for isolating RNA aptamers capable of cell-specific internalization in prostate cancer cells. (B) Visualization of aptamer-functionalized nanoparticle internalization by PC3 cells using confocal fluorescence microscopy. The nucleus is stained blue (DAPI), the cytoskeleton is stained red (rhodamine phalloidin), and the nanoparticles are green (NBD dye). Figure taken from reference [74, 108].
Figure 7
Figure 7
Tumor cell internalization of polymer-drug conjugates occurs through several possible mechanisms, including fluid-phase pinocytosis (in solution), non-specific membrane binding (due to hydrophobic or charge interactions) resulting in receptor-mediated pinocytosis, or ligand-receptor docking. The linker used to conjugate drug to the polymer allow for intracellular drug release based on a trigger such as exposure to lysosomal enzymes (e.g., Gly-Phe-Leu-Gly is cleaved by cathepsin B) or low pH (e.g., a hydrazone linker degrades in endosomes and lysosomes (pH 6.5 to <4.0)). Pharmacological targets in the cell are reached by the active or passive transport of drugs out of endosomal or lysosomal vesicles. Intracellular delivery allows drugs to bypass membrane efflux pumps such as p-glycoprotein that aid in drug resistance. Polymers that are not biodegradable can be removed from cells through exocytosis. Figure taken from reference [118].
Figure 8
Figure 8
The proton sponge effect allows for cationic nanoparticles to escape endosomal and lysosomal vesicles and enter the cytoplasm. When cationic nanoparticles enter acidic vesicles, unsaturated amino groups sequester protons supplied by v-ATPase (proton pump). Sequestered protons cause the pump to continue functioning, leading to the retention of chloride ions and water molecules. Eventually, osmotic swelling causes rupture of the vesicle and the cationic nanoparticles are able to enter the cytoplasm.
Figure 9
Figure 9
(a) Schematic of a QD-aptamer (doxorubicin) system capable of fluorescence resonance energy transfer (FRET). Doxorubicin is able to intercalate with the A10 PSMA aptamer bound to the QD surface, quenching both QD and doxorubicin fluorescence through a Bi-FRET mechanism (“OFF” state). (b) Aptamer targeting results in receptor-mediated endocytosis of QD-aptamer (doxorubicin) conjugates by cancer cells. Doxorubicin release from QD-aptamer (doxorubicin) conjugates results in fluorescence recovery by both QD and doxorubicin (“ON” state). LNCaP cells expressing PSMA were incubated with QD-aptamer (doxorubicin) for 0.5 h at 37 °C, washed two times with PBS buffer, and further incubated at 37 °C for (c) 0 h and (d) 1.5 h before imaging using confocal laser scanning microscopy. Doxorubicin is shown in red and QDs are shown in green. The lower right images of each panel represent the overlay of doxorubicin and QD fluorescent. The scale bar is 20 μm. Figure taken from reference [183].
Figure 10
Figure 10
Pt(IV)-PLA drug conjugates were blended with PLGA-PEG and docetaxel to form nanoparticles capable of delivering chemotherapy drug combinations. The nanoparticle surface was then functionalized with the A10 aptamer to target the nanoparticles to PSMA receptors. Figure taken from reference [192].
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer. 2005;5:161–171. - PubMed
    1. Jain KK. Role of nanobiotechnology in the development of personalized medicine. Nanomedicine (Lond) 2009;4:249–252. - PubMed
    1. Jain KK. Personalized medicine. Curr. Opin. Mol. Ther. 2002;4:548–558. - PubMed
    1. Vizirianakis IS. Nanomedicine and personalized medicine toward the application of pharmacotyping in clinical practice to improve drug-delivery outcomes. Nanomedicine. 2011;7:11–17. - PubMed
    1. Sakamoto JH, van de Ven AL, Godin B, Blanco E, Serda RE, Grattoni A, Ziemys A, Bouamrani A, Hu T, Ranganathan SI, De Rosa E, Martinez JO, Smid CA, Buchanan RM, Lee SY, Srinivasan S, Landry M, Meyn A, Tasciotti E, Liu X, Decuzzi P, Ferrari M. Enabling individualized therapy through nanotechnology. Pharmacol. Res. 2010;62:57–89. - PMC - PubMed

Publication types