Editorial pubs.acs.org/CR
Introduction: Nanoparticles in Medicine
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and drug delivery and magnetothermal treatments. The biosafety of magnetic nanoparticles is also discussed. Weissleder and co-workers review recent developments in magnetic nanoparticle-based POC diagnostics. The fundamentals of magnetic detection and actuation are discussed, followed by magnetic nanoparticle synthesis, surface modification, and bioconjugation chemistries. The clinical applications of magnetic nanoparticle-based POC diagnostics in infection, cancer, coagulation, and others are summarized. Sun, Yan, and co-workers provide a thorough review on lanthanide-based nanoparticles. The article discusses the applications of lanthanide nanoparticles in MRI, CT, and single photon emission computed tomography (SPECT) imaging, and recent progress on designing lanthanide upconversion nanoparticles and near-infrared emitting lanthanide nanoparticles for biosensing, bioimaging, and therapy. The article also discusses the applications of lanthanide nanoparticles in dual-modal and multimodal imaging, the use of nanoceria in nanomedicine, and biosafety evaluations of lanthanide nanomaterials. Dai and co-workers review the recent progress in imaging and therapy using carbon nanomaterials. The article summarizes the structures, properties, and surface functionalization of carbon nanomaterials, and it discusses fluorescence imaging, Raman imaging, transient absorption microscopy, photoacoustic imaging, and other nonoptical imaging modalities. The article highlights recent progress on drug and gene delivery, photoacoustic and photodynamic therapy, as well as in vitro cytotoxicity and in vivo toxicology results regarding various carbon nanomaterials. Kiessling, Lammers, and co-workers discuss noninvasive imaging of nanomedicines and nanotheranostics using a variety of modalities. The article discusses the use of these noninvasive imaging techniques, including PET, SPECT, CT, MRI, optical imaging, and ultrasound, for monitoring drug delivery, release, and efficacy. The detailed and quantitative information on the nanoparticle pharmacokinetics and biodistribution can guide the design of more powerful nanomedicines and nanotheranostics. For organic nanoparticles, Torchilin and co-workers provide a comprehensive review on recent advances in liposome formulations and their applications in medicine. The article gives an overview of liposome composition, preparation, and characterization, and then it discusses drug delivery using both passive, long-circulating liposomes and active and trigger-based targeting liposomes. Drug delivery with hybrid liposomes and via different routes of administration as well as the use of liposomes in molecular imaging and vaccine delivery are then discussed. Finally, the regulatory issues of liposomal drugs and broader nanomedicines are addressed. Elsabahy, Wooley, and co-workers review several recent advances in the design of polymeric nanoparticles for the
arly detection of many diseases, particularly cancers, is key to successful treatment. However, traditional diagnostic and imaging techniques cannot detect tumors in early development stages and have limited ability in differentiating benign and malignant lesions. In contrast, novel nanoparticle imaging agents can yield more sensitive and selective imaging of cancer and other diseased tissues. Nanoparticles also have the potential to be ideal carriers for delivering anticancer and other therapeutics to diseased sites with minimal collateral damage to normal tissues. The Nanoparticles in Medicine thematic issue provides a comprehensive assessment of the state-of-the-art of biological and biomedical applications of nanomaterials. The issue encompasses the unique capabilities of nanoparticles for in vitro detection, in vivo diagnosis, multimodal imaging, chemo-, photo-, gene-, and immunotherapy, theranostics, and their clinical translation, and it is organized into sections covering inorganic (metallic and metal oxide) nanoparticles, liposomes, organic nanoparticles, and hybrid nanoparticles. For inorganic nanoparticles, Xia and co-workers provide a comprehensive review of synthesis, surface modifications, and optical properties of a wide variety of Au nanomaterials. The article summarizes the applications of Au nanostructures in optical sensing/imaging, computed tomography (CT) imaging, PET imaging, Cerenkov Luminescence Imaging, drug delivery, and cancer therapy. Pharmacokinetics, biodistribution, and tumor targeting of Au nanostructures are also discussed. Lane, Qian, and Nie provide a review on surface-enhanced Raman scattering (SERS) properties and biomedical applications of Au and Ag nanoparticles. The article describes the major types of SERS-active nanostructures and summarizes the use of SERS nanoparticles for label-free molecular detection, in vitro diagnostics, in vivo spectroscopic detection, and imageguided cancer surgery. Mirkin and co-workers discuss nanoparticle-based methods for the detection of cancer by fluorescence spectroscopy. By tuning nanoparticle characteristics and their attached recognition moieties, nanoparticle probes can be used for detecting extracellular cancer biomarkers, cancer cells, and cancerous tissues in vivo. This nanoparticle-based early detection of cancer allows for therapeutic intervention in the early stages of the disease. Zhou, Gao, Liu, and Chen discussed the applications of Au nanoparticles in in vitro diagnostics (IVD). The article surveys the applications of Au nanoparticle IVDs based on localized surface plasmon resonance (LSPR), fluorescence resonance energy transfer (FRET), and electrochemical, SERS, and pointof-care (POC) assays. Challenges facing Au nanoparticle-based IVDs and potential solutions are discussed. Hyeon, Cheon, and co-workers review the development of magnetic iron oxide nanoparticles as MRI agents for sensitive and accurate diagnosis by optimizing the material synthesis and integrating with other imaging modalities. The article discusses the recent advances in magnetoresponsive therapeutic applications, including magnetomechanically targeted gene © 2015 American Chemical Society
Special Issue: Nanoparticles in Medicine Published: October 14, 2015 10407
DOI: 10.1021/acs.chemrev.5b00534 Chem. Rev. 2015, 115, 10407−10409
Chemical Reviews
Editorial
have largely been realized through reduced toxicity, but not through significantly enhanced efficacy. The lack of enhanced efficacy is likely due to the fact that the existing oncology nanoformulations are all monotherapies. To remedy this deficiency, several ongoing clinical trials are evaluating the feasibility of combining chemotherapeutic nanomedicines with radiotherapy or small molecule drugs (such as gemcitabine). There is thus an urgent need for the development of novel nanoparticle formulations that are capable of enhanced delivery and temporally controlled release of multiple synergistic therapeutics in order to achieve much enhanced therapeutic efficacy. In the area of nucleic acid delivery, the initial enthusiasm of siNRA-based cancer treatment has not led to much success, mainly due to the inability to simultaneously meet the requirements of enhanced cancer cell uptake via endocytosis and rapid endosomal escape to minimize the degradation of siRNA. Nanoparticles with the ability to accumulate in the tumor as well as to trigger endosomal escape are urgently needed in order to realize the promise of siRNA and other nucleic acid therapeutics. Such nanoparticles will also likely play a significant role in affording better therapeutic vaccines to further enhance the highly successful checkpoint inhibitorbased cancer immunotherapy. Nanoparticle-based in vitro diagnostics are likely to see major advances owing to the much lower regulatory barriers; however, FDA approval of IVDs by no means can guarantee commercial success in this area. Nanoparticle-based in vivo imaging agents will likely have to be piggybacked with nanotherapeutics in order to justify the huge financial burden for clinical trials. The comprehensive reviews in this issue will stimulate discussion and further developments of this active research field, spurring the clinical translation of novel diagnostics and therapeutics.
delivery of diagnostic and/or therapeutic agents. The various barriers toward the clinical development of these materials are also discussed. The applications of polymer nanoparticles in CT, SPECT, MRI, and multimodal imaging, in cardiovascular, cancer, and infectious disease therapy, and in theranostics are discussed in detail. Ng and Zheng provide a review on the applications of intermolecular dye interactions in organic nanoparticles for phototheranostic applications. The article focuses on the development of organic nanostructures with chromophores interacting via “through-space” mechanisms, and it discusses the optical imaging and therapy techniques relying on radiative emission, vibrational relaxation, and intersystem crossing/ triplet-state relaxation of the constituent chromophores. The exploitations of intermolecular dye interaction-dependent photophysical properties in developing novel photothermal therapy and photoacoustic imaging strategies are reviewed. Lächelt and Wagner discuss the delivery of nucleic acid therapeutics via complexation with polymeric carriers into polyplex nanoparticles. The article gives a brief overview on therapeutic nucleic acids and challenges for their delivery, followed by an in-depth discussion on polyplex-based nucleic acid delivery, ranging from delivery pathways, to cationic core polymers, to functional delivery domains, and to multifunctional dynamic polyplexes. The article also provides a perspective on the limited clinical success of therapeutic nucleic acids. For hybrid nanoparticles, He, Liu, and Lin summarize the development of nanoscale metal−organic frameworks (NMOFs) and nanoscale coordination polymers (NCPs) for cancer therapy and biomedical imaging. NMOFs and NCPs represent a novel class of hybrid nanomaterials that have been developed over the past decade. This article describes common strategies used for NMOF/NCP synthesis and for incorporation of imaging agents and drugs within NMOFs and NCPs as well as summarizes the applications of NMOFs and NCPs in drug delivery and therapy, imaging, and sensing. Irvine et al. review the development of synthetic nanoparticles for vaccines and immunotherapy. The article provides a brief description of key cellular actors in the immune system and summarizes the applications of various types of nanomaterials in developing vaccines and stimulating active immunotherapy. The article gives an overview of how interdisciplinary teams use nanomaterials as powerful tools to probe or manipulate immune responses for therapeutic purposes. Finally, Wang and co-workers provide a thorough review of recent progress on clinical translation of nanomedicine. The article examines preclinical evidence, chosen clinical path to translation, and clinical data of clinically approved nanomedicine products. The clinical data on nanomedicines that are under clinical investigation or failed clinical translation are also discussed. A bright outlook for the future of nanomedicine is given along with a few general directions for facilitating the translation of new nanomedicine products. The importance of nanoparticles in medicine has been validated by the clinical and commercial success of several oncology nanoformulations of existing chemotherapeutics, such as Doxil (PEGylated liposomal doxorubicin) and Abraxane (albumin-bound paclitaxel). However, none of the newer nanoparticle platforms, including inorganic particles, polymer micelles, and polymer conjugates, have yet received FDA approval in spite of extensive clinical testing. Furthermore, the clinical benefits of even the FDA-approved nanoformulations
Wenbin Lin*
University of Chicago
AUTHOR INFORMATION Corresponding Author
*E-mail:
[email protected]. Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS. The authors declare no competing financial interest. Biography
Wenbin Lin is the James Franck Professor of Chemistry and Comprehensive Cancer Center at the University of Chicago. His 10408
DOI: 10.1021/acs.chemrev.5b00534 Chem. Rev. 2015, 115, 10407−10409
Chemical Reviews
Editorial
research efforts focus on designing novel supramolecular systems and hybrid nanomaterials for applications in chemical and life sciences. He has published >250 papers and is among the 2015 list of highly cited chemists. (Group website: http://linlab.uchicago.edu/.)
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DOI: 10.1021/acs.chemrev.5b00534 Chem. Rev. 2015, 115, 10407−10409
