This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

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Analysis of nanoparticle delivery to tumours

Applications in Theranostics Guanying Chen,*,†,‡ Hailong Qiu,†,‡ Paras N. Prasad,*,‡,§ and Xiaoyuan Chen* †School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China ‡Department of Chemistry and the Institute for Lasers, Photonics, and Biophotonics, University at Buffalo, State University of New York, Buffalo, New York 14260, United States Department of Chemistry, Korea University, Seoul 136-701, Korea Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892-2281, United States

Upconversion Nanoparticles: Design, Nanochemistry, and Applications in Theranostics

Functional Nanomaterials for Phototherapies of Cancer

The nonradiative conversion of light energy into heat (photothermal therapy, PTT) or sound energy (photoacoustic imaging, PAI) has been intensively investigated for the treatment and diagnosis of cancer, respectively. By taking advantage of nanocarriers, both imaging and therapeutic functions together with enhanced tumour accumulation have been thoroughly studied to improve the pre-clinical efficiency of PAI and PTT. In this review, we first summarize the development of inorganic and organic nano photothermal transduction agents (PTAs) and strategies for improving the PTT outcomes, including applying appropriate laser dosage, guiding the treatment via imaging techniques, developing PTAs with absorption in the second NIR window, increasing photothermal conversion efficiency (PCE), and also increasing the accumulation of PTAs in tumours. Second, we introduce the advantages of combining PTT with other therapies in cancer treatment. Third, the emerging applications of PAI in cancer-related research are exemplified. Finally, the perspectives and challenges of PTT and PAI for combating cancer, especially regarding their clinical translation, are discussed. We believe that PTT and PAI having noteworthy features would become promising next-generation non-invasive cancer theranostic techniques and improve our ability to combat cancers.

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Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer

Photoacoustic imaging holds great promise for the visualization of physiology and pathology at the molecular level with deep tissue penetration and fine spatial resolution. To fully utilize this potential, photoacoustic molecular imaging probes have to be developed. Here, we introduce near-infrared light absorbing semiconducting polymer nanoparticles as a new class of contrast agents for photoacoustic molecular imaging. These nanoparticles can produce a stronger signal than the commonly used single-walled carbon nanotubes and gold nanorods on a per mass basis, permitting whole-body lymph-node photoacoustic mapping in living mice at a low systemic injection mass. Furthermore, the semiconducting polymer nanoparticles possess high structural flexibility, narrow photoacoustic spectral profiles and strong resistance to photodegradation and oxidation, enabling the development of the first near-infrared ratiometric photoacoustic probe for in vivo real-time imaging of reactive oxygen species--vital chemical mediators of many diseases. These results demonstrate semiconducting polymer nanoparticles to be an ideal nanoplatform for developing photoacoustic molecular probes.

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Semiconducting polymer nanoparticles as photoacoustic molecular imaging probes in living mice

Gold nanostructures have garnered considerable attention in recent years for their potential to facilitate both the diagnosis and treatment of cancer through their advantageous chemical and physical properties. The key feature of Au nanostructures for enabling this diverse array of biomedical applications is their attractive optical properties, specifically the scattering and absorption of light at resonant wavelengths due to the excitation of plasmon oscillations. This phenomenon is commonly known as localized surface plasmon resonance (LSPR) and is the source of the ruby red color of conventional Au colloids. The resonant wavelength depends on the size, shape, and geometry of the nanostructures, providing a set of knobs to manipulate the optical properties as needed. For in vivo applications, especially when optical excitation or transduction is involved, the LSPR peaks of the Au nanostructures have to be tuned to the transparent window of soft tissues in the near-infrared (NIR) region (from 700 to 900 ...

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Gold Nanocages: From Synthesis to Theranostic Applications

Gold nanocages have recently emerged as a novel class of photothermal transducers and drug carriers for cancer treatment. However, their pharmacokinetics and tumor targeting capability remain largely unexplored due to the lack of an imaging modality for quick and reliable mapping of their distributions in vivo. Herein, Au nanocages were prepared with controlled physicochemical properties and radiolabeled with 64Cu in high specific activities for in vivo evaluation using positron emission tomography (PET). Our pharmacokinetic studies with femtomolar administrations suggest that 30 nm nanocages had a greatly improved biodistribution profile than 55 nm nanocages, together with higher blood retention and lower hepatic and splenic uptakes. In a murine EMT-6 breast cancer model, the small cages also showed a significantly higher level of tumor uptake and a greater tumor-to-muscle ratio than the large cages. Quantitative PET imaging confirmed rapid accumulation and retention of Au nanocages inside the tumors. Th...

Evaluating the pharmacokinetics and in vivo cancer targeting capability of Au nanocages by positron emission tomography imaging.

The unique photophysical properties of noble metal nanoparticles contribute to their potential as photoactivated drug delivery vectors. Here we demonstrate the synthesis and characterization of 60–80 nm silver nanoparticles (SNPs) decorated with thiol-terminated photolabile DNA oligonucleotides. In vitro assays and fluorescent confocal microscopy of treated cell cultures show efficient UV-wavelength photoactivation of surface-tethered caged ISIS2302 antisense oligonucleotides possessing internal photocleavable linkers. As a demonstration of the advantages of these novel nanocarriers, we investigate properties including: enhanced stability to nucleases, increased hybridization activity upon photorelease, and efficient cellular uptake as compared to commercial transfection vectors. Their potential as multicomponent delivery agents for oligonucleotide therapeutics is shown through regulation of ICAM-1 (Intracellular Adhesion Molecule-1) silencing. Our results suggest a means to achieve light-triggered, spati...

Silver Nanoscale Antisense Drug Delivery System for Photoactivated Gene Silencing

Gold nanoparticles with tunable absorption and scattering properties have been developed as contrast agents for various optical imaging techniques. As a hybrid modality that combines the merits of both optical and ultrasonic imaging, photoacoustic (PA) imaging also benefits from the use of these nanoparticles to greatly enhance the contrast for visualization of structures and biomarkers in biological tissues. Gold nanocages characterized by hollow interiors, ultrathin and porous walls are of particular interest for in vivo PA imaging because of their compact sizes, bio-inertness and well-defined surface chemistry, as well as their strong and highly wavelength-tunable optical absorption in the near-infrared (NIR) optical window of soft tissues. This review discusses the application of gold nanocages as a new class of contrast agents for PA imaging in the context of cancer diagnosis.

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Gold nanocages as contrast agents for photoacoustic imaging

A system comprising 'signalling' and 'receiving' modules — where the receiving module circulating in the bloodstream is directed to the tumour by a cascade triggered by the signalling module — improves the targeting effect of a nanomedicine.

Paige Brown

Papers

Gold Nanocages: From Synthesis to Theranostic Applications

Evaluating the pharmacokinetics and in vivo cancer targeting capability of Au nanocages by positron emission tomography imaging.

Silver Nanoscale Antisense Drug Delivery System for Photoactivated Gene Silencing

Gold nanocages as contrast agents for photoacoustic imaging

Nanomedicine: Swarming towards the target