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*Division of Cardiology, Campus Box 8215, 660 Euclid Ave., Washington University School of Medicine, St. Louis, MO 63108. Tel: 314-454-7674...
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Theranostic Nanomedicine with Functional Nanoarchitecture

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laboratories, from both EPFL, Switzerland, and IFOM-IEO, Italy, reveal a protocol for the minimum concentration of nanoparticles that should be tested with RBCs to ensure the detection of free dye molecules. Brush polymers are quickly gaining interest in controlled therapeutic delivery.15 In another original paper, Dr. Chong Cheng and his collaborators from SUNY Buffalo report the synthesis of a degradable brush copolymer conjugated to paclitaxel. A grafting-onto polymerization approach and azide− alkyne click chemistry protocol were followed to synthesize these well-defined degradable polymeric constructs designed for sustained release of the hydrophobic drug. Cytotoxicity and cell internalization were tested in MCF-7 breast cancer cell line in collaboration with the laboratory of Dr. Paras Prasad at SUNY Buffalo. Dr. Luigi Bonacina from University of Geneva discusses the fascinating prospect of harmonic nanoparticles in theranostics. Compared to the other approaches, the harmonic nanoparticle approach is a nascent technology; however it is slowly gaining broad interest for clinical translation. Dr. Bonacina points out that the first true biomedical-oriented applications of nonlinear nanomedicine date back only a few years. However, these early works have already shown that the approach brings a new dimension to the whole theranostics area and offers great promise. Gold nanoparticles have shown unique potential for imaging and therapy. Dr. Paresh Ray’s group from Jackson State University reports star-shaped gold coated iron nanoparticles designed for the isolation of targeted circulating tumor cells. Ray’s work also shows a possibility of photothermal destruction of the cancer cells in vitro. The work describes the development of novel star morphology for the plasmonic-magnetic nanoparticles and their selectivity toward HER2 cells by S6 aptamer mediated active targeting. Dr. David Cormode from Mount Sinai School of Medicine and his collaborators provide a brief account of multifunctional gold nanoparticles that are being used for imaging (PAT, CT, fluorescence imaging etc.) and therapy (photothermal destruction). Finally, in a critical review article Dr. Jin-Woo Kim et al. from University of Arkansas introduces the nanotechnology-based theranostic approaches for real-time detection, characterization for circulating cancer, endothelial and bacterial cells. For the reader, this special issue illustrates a presentation of the advancements related to the field of theranostics, which I hope will stimulate experimentation to progress and tune these technologies for basic, translational and clinical applications.

his special issue of Molecular Pharmaceutics is dedicated to the topic of theranostics where we discuss the role of functional nanometer-sized agents in personalized medicine.1−3 Molecular imaging is defined as a noninvasive way to image cellular and subcellular events.4 Over the past two decades, the field has gained tremendous vigor with high potential for translational research. Major advancements in the areas of chemistry, molecular biology, genetics and engineering created unique opportunities for cross disciplinary work with the objective of driving clinical imaging strategies for early, sensitive detection, diagnosis and treatment of a disease at the molecular and cellular level with uncompromised specificity.5,6 The unprecedented potential of nanoparticles for both detection and drug delivery has been well established.7−9 Myriad advancement has been made toward the development of defined nanostructure for performing dual function, i.e., imaging and therapy (theranostics). Biological and biophysical obstacles are overcome by the incorporation of homing agents, contrast materials and therapeutics into the nano platform, which allow for theranostic applications.10−12 In our perspective article, Dr. Sonke Svenson of Drug Delivery Solutions LLC shares his vast experience in bringing nanotechnology to the market. In this lead paper he illustrates the concept of theranostics and introduces the readers to the opportunities and challenges created by these nanocarriers for clinical translation. He points out that there are over 40 nanoformulations that are being investigated at different levels of clinical development. Interestingly, the majority of them rely on passive targeting approaches. Dr. Xiankai Sun from University of Texas Southwestern Medical Center discusses the potential application of dendrimers for the diagnosis and treatment of prostate cancer. While the Sun lab report emphasizes nuclear medicine, his team and collaborators describe relevant chemical strategies for the design and syntheses of dendritic nanostructures. This review article further exemplifies the different targeting approaches (e.g., type II transmembrane glycoprotein PSMA, integrin αvβ3), diagnostic tactics (MRI, CT, PET, SPECT, optical etc.) and therapeutics (chemotherapeutics, genetherapy, immunotherapy, radiotherapy etc.). Size dictates the in vivo characteristics of nanoparticles designed for targeting specific biological markers and strongly associates with its biodistributive nature, tissue accumulation and cellular uptake.13,14 The work from Dr. Jianjuan Cheng and his team further supports this claim. In this original report, the Cheng lab from UIUC looks at the size-dependent tumor penetration of camptothecin-conjugated-silica nanoparticles in the treatment of subcutaneous LLC tumor mice. Results indicate that the 50 nm sized nanoagents showed higher antitumor efficacy in comparison to their larger (200 nm) analogues. Dr. Francesco Stellacci, a recognized leader in this field, reports that incubation of nanoparticles with erythrocytes is an excellent approach to determine if unbound optical probe is present. In this interesting fundamental work, the reporting © 2013 American Chemical Society

Dipanjan Pan,* Guest Editor

Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63108, United States Special Issue: Theranostic Nanomedicine with Functional Nanoarchitecture Published: March 4, 2013 781

dx.doi.org/10.1021/mp400044j | Mol. Pharmaceutics 2013, 10, 781−782

Molecular Pharmaceutics



Editorial

AUTHOR INFORMATION

Corresponding Author

*Division of Cardiology, Campus Box 8215, 660 Euclid Ave., Washington University School of Medicine, St. Louis, MO 63108. Tel: 314-454-7674. Fax: 314-454-5265. E-mail: [email protected]. Notes

Views expressed in this editorial are those of the author and not necessarily the views of the ACS.



REFERENCES

(1) Shin, S. J.; Beech, J. R.; Kelly, K. A. Targeted nanoparticles in imaging: paving the way for personalized medicine in the battle against cancer Integr Biol (Camb) 2012 Dec 17, 5 (1), 29−42. (2) Pang, T. Theranostics, the 21st century bioeconomy and ’one health’. Expert Rev Mol Diagn. 2012 Nov, 12 (8), 807−9. (3) Lee, D. Y.; Li, K. C. Molecular theranostics: a primer for the imaging professional. AJR Am J Roentgenol. 2011 Aug, 197 (2), 318− 24. (4) James, M. L.; Gambhir, S. S. A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev. 2012 Apr, 92 (2), 897−965. (5) Pan, D.; Lanza, G. M.; Wickline, S. A.; Caruthers, S. D. Nanomedicine: perspective and promises with ligand-directed molecular imaging. Eur J Radiol. 2009 May, 70 (2), 274−85. (6) Alberti, C. From molecular imaging in preclinical/clinical oncology to theranostic applications in targeted tumor therapy. Eur Rev Med Pharmacol Sci. 2012 Dec, 16 (14), 1925−33. (7) Wang, L. S.; Chuang, M. C.; Ho, J. A. Nanotheranostics–a review of recent publications. Int J Nanomedicine. 2012, 7, 4679−95. (8) Lammers, T.; Aime, S.; Hennink, W. E.; Storm, G.; Kiessling, F. Theranostic nanomedicine. Acc. Chem. Res. 2011 Oct 18, 44 (10), 1029−38. (9) Cabral, H.; Nishiyama, N.; Kataoka, K. Supramolecular nanodevices: from design validation to theranostic nanomedicine. Acc. Chem. Res. 2011 Oct 18, 44 (10), 999−1008. (10) Kunjachan, S.; Jayapaul, J.; Mertens, M. E.; Storm, G.; Kiessling, F.; Lammers, T. Theranostic systems and strategies for monitoring nanomedicine-mediated drug targeting. Curr Pharm Biotechnol. 2012 Mar, 13 (4), 609−22. (11) Pan, D.; Caruthers, S. D.; Chen, J.; Winter, P. M.; SenPan, A.; Schmieder, A. H.; Wickline, S. A.; Lanza, G. M. Nanomedicine strategies for molecular targets with MRI and optical imaging. Future Med Chem. 2010 Mar, 2 (3), 471−90. (12) Lanza, G. M. ICAM-1 and nanomedicine: nature’s doorway to the extravascular tissue realm. Arterioscler Thromb Vasc Biol. 2012 May, 32 (5), 1070−1. (13) Pan, D.; Pramanik, M.; Senpan, A.; Ghosh, S.; Wickline, S. A.; Wang, L. V.; Lanza, G. M. Near infrared photoacoustic detection of sentinel lymph nodes with gold nanobeacons. Biomaterials 2010 May, 31 (14), 4088−93. (14) Albanese, A.; Tang, P. S.; Chan, W. C. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng. 2012, 14, 1−16. (15) Elsabahy, M.; Wooley, K. L. Design of polymeric nanoparticles for biomedical delivery applications. Chem Soc Rev. 2012 Apr 7, 41 (7), 2545−61.

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dx.doi.org/10.1021/mp400044j | Mol. Pharmaceutics 2013, 10, 781−782