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WIREs Nanomed Nanobiotechnol

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The NCI Alliance for Nanotechnology in Cancer: achievement and path forward

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Krzysztof Ptak, Dorothy Farrell, Nicholas J. Panaro, Piotr Grodzinski, Anna D. Barker

Published Online: Jun 08 2010

DOI: 10.1002/wnan.98

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Nanotechnology is a ‘disruptive technology’, which can lead to a generation of new diagnostic and therapeutic products, resulting in dramatically improved cancer outcomes. The National Cancer Institute (NCI) of National Institutes of Health explores innovative approaches to multidisciplinary research allowing for a convergence of molecular biology, oncology, physics, chemistry, and engineering and leading to the development of clinically worthy technological approaches. These initiatives include programmatic efforts to enable nanotechnology as a driver of advances in clinical oncology and cancer research, known collectively as the NCI Alliance for Nanotechnology in Cancer (ANC). Over the last 5 years, ANC has demonstrated that multidisciplinary approach catalyzes scientific developments and advances clinical translation in cancer nanotechnology. The research conducted by ANC members has improved diagnostic assays and imaging agents, leading to the development of point‐of‐care diagnostics, identification and validation of numerous biomarkers for novel diagnostic assays, and the development of multifunctional agents for imaging and therapy. Numerous nanotechnology‐based technologies developed by ANC researchers are entering clinical trials. NCI has re‐issued ANC program for next 5 years signaling that it continues to have high expectations for cancer nanotechnology's impact on clinical practice. The goals of the next phase will be to broaden access to cancer nanotechnology research through greater clinical translation and outreach to the patient and clinical communities and to support development of entirely new models of cancer care. WIREs Nanomed Nanobiotechnol 2010 2 450–460

Figure 1.

NCI Alliance for Nanotechnology in Cancer awarded institutions (2005–2010): Centers of Cancer Nanotechnology Excellence (in red) and Cancer Nanotechnology Platform Partnerships (in blue).

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Figure 2.

Research Articles in Cancer Nanotechnology from 2002 to 2009. The information was retrieved from MEDLINE/PubMED indexed articles using the U.S. National Library of Medicine's Medical Subject Headings (MESH) terminology related to ‘cancer’ and ‘nanotechnology’.

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Figure 3.

Particle Replication In Non‐wetting Templates (PRINT) and their uptakes by HeLa cells. (A) Scanning electron microscope (SEM) images of particles of various sizes, shapes, and compositions prepared via the PRINT process: (a) hydrogel rods containing antisense oligonucleotide; (b) crosslinked degradable matrix cubes containing doxorubicin HCl; (c) abraxane harvested onto medical adhesive; (d) insulin particles harvested onto a medical adhesive; (e) hydrogel ‘boomerangs’ containing 15 wt% iron oxide; (f) hydrogel cylinders containing 10 wt% Omniscan. (B) Transmission electron microscopy (TEM) image showing HeLa cell internalization of 150 × 450 nm (top) or 200 × 200 nm (bottom) cylindrical particles fabricated via the PRINT process. (Panels A and B reprinted with permission from Ref 6. Copyright © 2009 John Wiley & Sons, Inc.).

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Figure 4.

Schematic representation of the PSA Au‐NP probes (Upper) and the PSA bio‐barcode assay (Lower). (Upper) Barcode DNA‐functionalized Au‐NPs (30 nm) are conjugated to PSA‐specific antibodies through barcode terminal tosyl (Ts) modification to generate the coloaded PSA Au‐NP probes. In a second step, the PSA Au‐NP probes are passivated with BSA. (Lower) The bio‐barcode assay is a sandwich immunoassay. First, MMPs surfacefunctionalized with monoclonal antibodies to PSA are mixed with the PSA target protein. The MMP‐PSA hybrid structures are washed free of excess serum components and resuspended in buffer. Next PSA Au‐NP probes are added to sandwich the MMP‐bound PSA. Again after magnetic separation and wash steps, the PSA‐specific DNA barcodes are released into solution and detected using the scanometric assay, which takes advantage of Au‐NP catalyzed silver enhancement. Approximately 1/2 of the barcode DNA sequence (green) is complementary to the ‘universal’ scanometric Au‐NP probe DNA, and the other 1/2 (purple) is complementary to a chip‐surface immobilized DNA sequence that is responsible for sorting and binding barcodes complementary to the PSA barcode sequence. (Reprinted with permission from Ref 18. Copyright © 2009 National Academy of Science USA).

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Figure 5.

Schematic of how the targeted nanoparticles function. (a) Nanoparticles are assembled from the four components (see Figure 2). (b) Aqueous solutions of nanoparticles are infused into patients. (c) The nanoparticles circulate in the blood of the patient and escape via the ‘leaking’ blood vessels in tumors. (d) Nanoparticles penetrate though the tumor and enter into cells by receptor‐mediated endocytosis (transmission electron micrograph of 50 nm nanoparticles entering a cancer cell). Note that the nanoparticles enter and are initially located in vesicles within the cell and must escape and disassemble to deliver their payload. (e) Targeted nanoparticles can have numerous interactions (e.g., Tf with its receptor) on the surface of the cancer cell that then stimulate entrance into the cell. (Reprinted with permission from Ref 30. Copyright © 2009 American Chemical Society).

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Figure 6.

[¹⁸F]FAC has better selectivity for lymphoid organs compared with other PET probes for nucleoside metabolism and glycolysis. C57/BL6 mice were scanned by microPET‐CT using [¹⁸F]FAC, [¹⁸F]FLT, [¹⁸F]DFMAU and [¹⁸F]FDG. Mice were imaged 60 min after intravenous injection of probes. B: bone; BL: bladder; BR: brain; GB: gall bladder; GI: gastrointestinal tract; H: heart; K: kidney; L: liver; LU: lung; SP: spleen; Thy: thymus; BM: bone marrow; ST: stomach. (Adopted by permission from Ref 33. Copyright © 2008 Nature Publishing Group).

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works at the interface of biotechnology and materials science. His lab is researching many topics, such as investigating the mechanism of release from polymeric delivery systems with concomitant microstructural analysis and mathematical modeling; studying applications of these systems including the development of effective long-term delivery systems for insulin, anti-cancer drugs, growth factors, gene therapy agents and vaccines; developing controlled release systems that can be magnetically, ultrasonically, or enzymatically triggered to increase release rates; synthesizing new biodegradable polymeric delivery systems which will ultimately be absorbed by the body; creating new approaches for delivering drugs such as proteins and genes across complex barriers such as the blood-brain barrier, the intestine, the lung and the skin; stem cell research including controlling growth and differentiation; and creating new biomaterials with shape memory or surface switching properties.

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