Imaging and drug delivery using theranostic nanoparticles

Abstract

Nanoparticle technologies are significantly impacting the development of both therapeutic and diagnostic agents. At the intersection between treatment and diagnosis, interest has grown in combining both paradigms into clinically effective formulations. This concept, recently coined as theranostics, is highly relevant to agents that target molecular biomarkers of disease and is expected to contribute to personalized medicine. Here we review state-of-the-art nanoparticles from a therapeutic and a diagnostic perspective and discuss challenges in bringing these fields together. Major classes of nanoparticles include, drug conjugates and complexes, dendrimers, vesicles, micelles, core-shell particles, microbubbles, and carbon nanotubes. Most of these formulations have been described as carriers of either drugs or contrast agents. To observe these formulations and their interactions with disease, a variety of contrast agents have been used, including optically active small molecules, metals and metal oxides, ultrasonic contrast agents, and radionuclides. The opportunity to rapidly assess and adjust treatment to the needs of the individual offers potential advantages that will spur the development of theranostic agents.

Fig. 1

Typical molecular imaging instruments and images representative of each modality. a) MRI [reprinted with permission from Macmillan Publishers Ltd: [164], © (2007); Image of instrument courtesy of Bruker Biospin Corporation.], b) computed tomography [reprinted from [152], © (2010) with permission from Elsevier; Image of instrument courtesy of Siemens.], c) positron emission tomography [reprinted by permission from Macmillan Publishers Ltd.: [153], © 2008; Image of instrument courtesy of Siemens.], d) single photon emission computed tomography [Reprinted by permission from Macmillan Publishers Ltd: [165], © (2008); Image of instrument courtesy of GE Healthcare.], e) optical imaging [reprinted by permission from Macmillan Publishers Ltd.: [154], © (2006); Image of instrument courtesy of Caliper Life Sciences.], f) ultrasound [reprinted from 155; Image of instrument courtesy of VisualSonics].

Fig. 2

Structural representations of nanoparticle classes functionalized for theranostics. Schematics of a functionalized a) drug conjugate; b) dendrimer; c) vesicle; d) micelle; e) core–shell nanoparticle; f) microbubble; and g) carbon nanotube.

Fig. 3

Several examples of nanoparticle contrast agents and TNPs. a) MR images and their color maps (tumor region) of cancer-targeting events of antibody (herceptin) directed multifunctional magneto-polymeric nanohybrid (MMPN) (i–iv) and non-targeted MMPNs (v–viii) in NIH3T6.7 cells implanted in mice at various time intervals. Tumor growth inhibition was demonstrated ([156], copyright Wiley–VCH Verlag GmbH & Co. KGaA. Reproduced with permission). b) In vivo MRI of mice bearing subcutaneous LS174T human colorectal adenocarcinoma (arrows). A significant drop in T2 relaxivity indicated successful probe delivery (covalently linked siRNA to a magnetic nanoparticle) which induces tumor silencing [reprinted by permission from Macmillan Publishers Ltd.: [157], © (2007). c) In vivo NIRF imaging of U87MG tumor-bearing mice injected with 200 pmol of QD705–RGD or QD705. Arrows indicate tumors (reprinted with permission from [158], © 2006 American Chemical Society). d) MicroPET images of two mice at various time points post tailvein injection of 64Cu-labeled single-walled CNT–PEG2000 and single-walled CNT–PEG5400, respectively. The arrows point to the tumors (reprinted by permission from Macmillan Publishers Ltd.: [147], © (2007).