Nanotheranostics--a review of recent publications

Abstract

Theranostics is referred to as a treatment strategy that combines therapeutics with diagnostics, aiming to monitor the response to treatment and increase drug efficacy and safety, which would be a key part of personalized medicine and require considerable advances in predictive medicine. Theranostics associates with both a diagnosis that tests patients for possible reactions to taking new medication and targeted drug delivery based on the test results. Emerging nanotechnology provides a great deal of opportunity to design and develop such combination agents, permitting the delivery of therapeutics and concurrently allowing the detection modality to be used not only before or after but also throughout the entire treatment regimen. The introduction of nanotheranostics into routine health care has still a long way to go, since evaluations on cytotoxicity, genotoxicity, and immunotoxicity of prospective nanotheranostics, demonstration of cost-effectiveness, and availability of appropriate accessible testing systems are still required. An extensive review, from a chemistry point of view, of the recent development of nanotheranostics and its in vitro and in vivo applications are herein presented.

Keywords: diagnostics; nanomaterial; theranostics; therapeutics.

Figure 1

(A) Schematic representation of MMP-AuNR for simultaneous imaging and photothermal therapy; (B) fluorescence spectra of MMP-AuNR in the presence of MMP-2 enzyme and dithiothreitol; (C) temperature increase of MMP-AuNR as a function of laser irradiation time; (D) NIRF tomographic images of SCC-7 tumor–bearing mice after intratumoral injection of the MMP-AuNR probe without (1) and with (2) inhibitor; (E) optical and NIRF images of excised tumor after injection of MMP-AuNR without and with MMP-2 inhibitor; (F) infrared thermal images of tumor-bearing mice according to different laser irradiation times; (G) optical images of exterior of SCC-7 tumor irradiated by laser; histology (right) and dark-field image (lower) of tumor after treatment are also presented. Reprinted with permission from Yi DK, Sun IC, Ryu JH, et al. Matrix metalloproteinase sensitive gold nanorod for simultaneous bioimaging and photothermal therapy of cancer. Bioconjug Chem. Copyright © 2010 American Chemical Society. Abbreviations: MMP-AuNR, matrix metalloprotease–sensitive gold nanorod; SCC, squamous cell carcinoma; NIRF, near-infrared fluorescence.

Figure 2

(A) Schematic illustration of anti-HER2/neu antibody–modified pH-sensitive drug-releasing magnetic nanoparticles (HER-DMNPs) for cancer therapy followed by magnetic resonance imaging (MRI); (B) color-coded T2-weighted MR images of tumor-bearing mice after the intravenous injection of HER-DMNPs and IRR-DMNPs at various time intervals, respectively; tumor regions are indicated with a white-dashed boundary; (C) pH-sensitive drug release profiles of the DMNPs over 5 days (black circle, pH 5.5; dark-gray triangle, pH 7.4; gray square, pH 9.8); (D) comparative therapeutic efficacy study in the in vivo model (black circle, HER-DMNPs; dark-gray triangle, IRR-DMNPs; gray square, doxorubicin; white diamond, saline); black arrow indicates the day of cancer cells (NIH3T6.7 cells) implantation in mice. Reprinted from Adv Mater. 2011;23(21):2436–2442. Lim EK, Huh YM, Yang J, Lee K, Suh JS, Haam S. pH-Triggered drug-releasing magnetic nanoparticles for cancer therapy guided by molecular imaging by MRI. © 2011 with permission from Wiley.

Figure 3

(A) Schematic illustration of tumor-primed delivery of NIR optical imaging agent (DiR) by a tandem of three-in-one PEG-b-PLA and PEG-b-PCL micelles; (B) whole-body NIR optical images of DiR (solid tumors in the right flank) after a midline incision in the abdomen; color alteration from blue to red indicates increased average radiant efficiency; (C) laser scanning confocal microscopic images of tumor tissue (60× magnification); DiR is shown in red, and nuclei of cells are in blue (DAPI); (D) summarized histograms of ex vivo NIR optical imaging of DiR after treatment with empty PEG-b-PLA micelles (vehicle), and micelle-encapsulated paclitaxel (PTX), or PTX/17-AAG/RAPA, injected intravenously 48 hours before the injection of DiR-containing PEG-b-PCL micelles (mean ± SD; n = 3; *P < 0.05, **P < 0.01, ***P < 0.0001); (E) apoptosis index recorded in immunohistochemical analysis of apoptosis (mean ± SD; n = 3; *P < 0.05, ***P < 0.0001). Notes: (B and C) Ex vivo and in vitro tests treated with vehicle control (left), PEG-b-PLA micelles carrying PTX (middle), and three-in-one PEG-b-PLA micelles carrying PTX/17-AAG/RAPA (right); Reprinted with permission from Cho H, Kwon GS. Polymeric micelles for neoadjuvant cancer therapy and tumor-primed optical imaging. ACS Nano. Copyright © 2011 American Chemical Society. Abbreviations: NIR, near infrared; PEG-b-PLA, polyethylene glycol polylactic acid; PCL, polycaprolactone.

Figure 4

(A) Scheme of an NGS with PEG functionalization and labeled by Cy7; (B) temperature-change curves of NGS-PEG solution and water exposed to 808-nm laser at power density of 2 W/cm²; rapid rise in temperature was noted for the NGS-PEG solution, in marked contrast to the water temperature, which showed little change during the laser irradiation; (C) spectrally unmixed in vivo fluorescence images of 4T1 tumor bearing Balb/c mice, KB, and U87MG tumor–bearing nude mice at different time points post-injection of NGS-PEG-Cy7; high tumor uptake of NGS-PEG-Cy7 was observed for all three tumor models; (D) tumor-growth curves of different groups after treatment, tumor volumes normalized to initial sizes; while injection of NGS-PEG by itself or laser irradiation on uninjected mice did not affect tumor growth, tumors in the treated group were completely eliminated after NGS-PEG injection and following NIR laser irradiation; (E) survival curves of mice bearing 4T1 tumor after various treatments; NGS-PEG-injected mice after photothermal therapy survived over 40 days without a single death. Reprinted with permission from Yang K, Zhang S, Zhang G, Sun X, Lee ST, Liu Z. Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett. Copyright © 2010 American Chemical Society. Abbreviations: NGS, nanographene sheet; PEG, polyethylene glycol; NIR, near infrared.

Figure 5

(A) Schematic representation of AuNR-MMSNEs: numbers of AuNRs being capped on the outer surface of a magnetite core/mesoporous silica shell; (B) In vivo magnetic resonance imaging of a mouse before and after intratumoral injection of AuNR-MMSNEs; (C) in vitro release profiles of Au NR-MMSNE-DOX using dialysis membrane against phosphate-buffered saline solution at pH 7.4 and 5.5; (D) cell viabilities for MCF-7 cells treated with different concentrations of AuNR-MMSNEs after incubation for 24 hours, after laser exposure for 5 minutes; (E) comparison of inhibition rates for MCF-7 cells treated by AuNR-MMSNE-NIR (purple), AuNR-MMSNE-DOX (red), and AuNR-MMSNE-DOX-NIR (green); for photothermal treatment, the media were under 808-nm laser irradiation for 5 minutes at different power intensities, corresponding to maximum temperature increases to 39°C, 42°C and 45°C. Reprinted from Biomaterials. 2012;33(3):989–998. Ma M, Chen H, Chen Y, et al. Au capped magnetic core/mesoporous silica shell nanoparticles for combined photothermo-/chemo-therapy and multimodal imaging © 2012 with permission from Elsevier. Abbreviations: AuNR-MMSNEs, gold nanorod-capped magnetic core/mesoporous silica shell nanoellipsoids; DOX, doxorubicin; NIR, near infrared.