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Rapid sequestration and prolonged retention of intravenously injected nanoparticles by the liver and spleen (reticuloendothelial system (RES)) presents a major barrier to effective delivery to the target site and hampers clinical translation of nanomedicine. Inspired by biological macromolecular drugs, synthesis of ultrasmall (diameter ≈12-15 nm) porous silica nanoparticles (UPSNs), capable of prolonged plasma half-life, attenuated RES sequestration, and accelerated hepatobiliary clearance, is reported. The study further investigates the effect of tumor vascularization on uptake and retention of UPSNs in two mouse models of triple negative breast cancer with distinctly different microenvironments. A semimechanistic mathematical model is developed to gain mechanistic insights into the interactions between the UPSNs and the biological entities of interest, specifically the RES. Despite similar systemic pharmacokinetic profiles, UPSNs demonstrate strikingly different tumor responses in the two models. Histopathology confirms the differences in vasculature and stromal status of the two models, and corresponding differences in the microscopic distribution of UPSNs within the tumors. The studies demonstrate the successful application of multidisciplinary and complementary approaches, based on laboratory experimentation and mathematical modeling, to concurrently design optimized nanomaterials, and investigate their complex biological interactions, in order to drive innovation and translation., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

DNA aptamers are integrated into synthetic hydrogel networks with the aim of creating hydrogels that undergo volume changes when exposed to target molecules. Specifically, single-stranded DNA aptamers in cDNA-bound, extended state are incorporated into hydrogel networks as cross-links, so that the nanoscale conformational change of DNA aptamers upon binding to target molecules will induce macroscopic volume decreases of hydrogels. Hydrogels incorporating adenosine triphosphate (ATP)-binding aptamers undergo controllable volume decreases of up to 40.3 ± 4.6% when exposed to ATP, depending on the concentration of DNA aptamers incorporated in the hydrogel network, temperature, and target molecule concentration. Importantly, this approach can be generalized to aptamer sequences with distinct binding targets, as demonstrated here that hydrogels incorporating an insulin-binding aptamer undergo volume changes in response to soluble insulin. This work provides an example of bioinspired hydrogels that undergo macroscopic volume changes that stem from conformational shifts in resident DNA-based cross-links., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Noninvasive dynamic positron emission tomography (PET) imaging was used to investigate the balance between renal clearance and tumor uptake behaviors of polyethylene glycol (PEG)-modified porphyrin nanoparticles (TCPP-PEG) with various molecular weights. TCPP-PEG 10K nanoparticles with clearance behavior would be a good candidate for PET image-guided photodynamic therapy.

Macrocyclic chelators have been widely employed in the realm of nanoparticle-based positron emission tomography (PET) imaging, whereas its accuracy remains questionable. Here, we found that 64 Cu can be intrinsically labeled onto nanographene based on interactions between Cu and the π electrons of graphene without the need of chelator conjugation, providing a promising alternative radiolabeling approach that maintains the native in vivo pharmacokinetics of the nanoparticles. Due to abundant π bonds, reduced graphene oxide (RGO) exhibited significantly higher labeling efficiency in comparison with graphene oxide (GO) and exhibited excellent radiostability in vivo. More importantly, nonspecific attachment of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) on nanographene was observed, which revealed that chelator-mediated nanoparticle-based PET imaging has its inherent drawbacks and can possibly lead to erroneous imaging results in vivo., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

While position emission tomography (PET) is an important molecular imaging technique for both preclinical research and clinical disease diagnosis/prognosis, chelator-free radiolabeling has emerged as a promising alternative approach to label biomolecules or nanoprobes in a facile way. Herein, starting from bottom-up synthesized WS 2 nanoflakes, this study fabricates a unique type of WS 2 /WO x nanodots, which can function as inherent hard oxygen donor for stable radiolabeling with Zirconium-89 isotope ( 89 Zr). Upon simply mixing, 89 Zr can be anchored on the surface of polyethylene glycol (PEG) modified WS 2 /WO x (WS 2 /WO x -PEG) nanodots via a chelator-free method with surprisingly high labeling yield and great stability. A higher degree of oxidation in the WS 2 /WO x -PEG sample (WS 2 /WO x (0.4)) produces more electron pairs, which would be beneficial for chelator-free labeling of 89 Zr with higher yields, suggesting the importance of surface chemistry and particle composition to the efficiency of chelator-free radiolabeling. Such 89 Zr-WS 2 /WO x (0.4)-PEG nanodots are found to be an excellent PET contrast agent for in vivo imaging of tumors upon intravenous administration, or mapping of draining lymph nodes after local injection., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Edible, surfactant-stripped, frozen micelles are formed from pheophytin (demetallated chlorophyll), a pigment that is naturally consumed in human diets. Pheophytin nanoparticles pass completely and safely through the gastrointestinal tract and enable trimodal gut contrast imaging via photoacoustic, fluorescence, and positron emission tomography techniques., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A systematic study of in vitro and in vivo behavior of biodegradable mesoporous silica nanoparticles (bMSNs), designed to carry multiple cargos (both small and macromolecular drugs) and subsequently self-destruct following release of their payloads, is presented. Complete degradation of bMSNs is seen within 21 d of incubation in simulated body fluid. The as-synthesized bMSNs are intrinsically radiolabeled with oxophilic zirconium-89 ( 89 Zr, t = 78.4 h) radionuclide to track their in vivo pharmacokinetics via positron emission tomography imaging. Rapid and persistent CD105 specific tumor vasculature targeting is successfully demonstrated in murine model of metastatic breast cancer by using TRC105 (an anti-CD105 antibody)-conjugated bMSNs. This study serves to illustrate a simple, versatile, and readily tunable approach to potentially overcome the current challenges facing nanomedicine and further the goals of personalized nanotheranostics.1/2 = 78.4 h) radionuclide to track their in vivo pharmacokinetics via positron emission tomography imaging. Rapid and persistent CD105 specific tumor vasculature targeting is successfully demonstrated in murine model of metastatic breast cancer by using TRC105 (an anti-CD105 antibody)-conjugated bMSNs. This study serves to illustrate a simple, versatile, and readily tunable approach to potentially overcome the current challenges facing nanomedicine and further the goals of personalized nanotheranostics.

Optical imaging has been the primary imaging modality for nearly all of the renal clearable nanoparticles since 2007. Due to the tissue depth penetration limitation, providing accurate organ kinetics non-invasively has long been a huge challenge. Although a more quantitative imaging technique has been developed by labeling nanoparticles with single-photon emission computed tomography (SPECT) isotopes, the low temporal resolution of SPECT still limits its potential for visualizing the rapid dynamic process of renal clearable nanoparticles in vivo. The dynamic positron emission tomography (PET) imaging of renal clearable gold (Au) nanoparticles by labeling them with copper-64 ((64) Cu) to form (64) Cu-NOTA-Au-GSH is reported. Systematic nanoparticle synthesis and characterizations are performed to demonstrate the efficient renal clearance of as-prepared nanoparticles. A rapid renal clearance of (64) Cu-NOTA-Au-GSH is observed (>75%ID at 24 h post-injection) with its elimination half-life calculated to be less than 6 min, over 130 times shorter than previously reported similar nanoparticles. Dynamic PET imaging not only addresses the current challenges in accurately and non-invasively acquiring the organ kinetics, but also potentially provides a highly useful tool for studying renal clearance mechanism of other ultra-small nanoparticles, as well as the diagnosis of kidney diseases in the near future., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Multifunctional theranostic agents have become rather attractive to realize image-guided combination cancer therapy. Herein, we develop a novel method to synthesize Bi 2 Se 3 nanosheets decorated with mono-dispersed FeSe 2 nanoparticles (FeSe 2 /Bi 2 Se 3 ) for tetra-modal image-guided combined photothermal & radiation tumor therapy. Interestingly, upon addition of Bi(NO 3 ) 3 , pre-made FeSe 2 nanoparticles via cation exchange would be gradually converted into Bi 2 Se 3 nanosheets, on which remaining FeSe 2 nanoparticles are decorated. The yielded FeSe 2 /Bi 2 Se 3 composite-nanostructures were then modified with polyethylene glycol (PEG). Taking advantages of the high r 2 relaxivity of FeSe 2 , the X-ray attenuation ability of Bi 2 Se 3 , the strong near-infrared (NIR) optical absorbance of the whole nanostructure, as well as the chelate-free radiolabeling of 64 Cu on FeSe 2 /Bi 2 Se 3 -PEG, in vivo magnetic resonance (MR)/computer tomography (CT)/photoacoustic (PA)/position emission tomography (PET) multimodal imaging was carried out, revealing efficient tumor homing of FeSe 2 /Bi 2 Se 3 -PEG after intravenous injection. Utilizing the intrinsic physical properties of FeSe 2 /Bi 2 Se 3 -PEG, in vivo photothermal & radiation therapy to achieve synergistic tumor destruction was then realized, without causing obvious toxicity to the treated animals. Our work presents a unique method to synthesize composite-nanostructures with highly integrated functionalities, promising not only for nano-biomedicine, but also potentially for other different nanotechnology fields.

Although chelator-based radiolabeling techniques have been used for decades, concerns about the complexity of coordination chemistry, possible altering of pharmacokinetics of carriers, and potential detachment of radioisotopes during imaging have driven the need for developing a simple yet better technique for future radiolabeling. Here, the emerging concept of intrinsically radiolabeled nanoparticles, which could be synthesized using methods such as hot-plus-cold precursors, specific trapping, cation exchange, and proton beam activation, is introduced. Representative examples of using these multifunctional nanoparticles for multimodality molecular imaging are highlighted together with current challenges and future research directions. Although still in the early stages, design and synthesis of intrinsically radiolabeled nanoparticles has shown attractive potential to offer easier, faster, and more specific radiolabeling possibilities for the next generation of molecular imaging., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Copper sulfide (CuS) nanoparticles have attracted increasing attention from biomedical researchers across the globe, because of their intriguing properties which have been mainly explored for energy- and catalysis-related applications to date. This focused review article aims to summarize the recent progress made in the synthesis and biomedical applications of various CuS nanoparticles. After a brief introduction to CuS nanoparticles in the first section, we will provide a concise outline of the various synthetic routes to obtain different morphologies of CuS nanoparticles, which can influence their properties and potential applications. CuS nanoparticles have found broad applications in vitro, especially in the detection of biomolecules, chemicals, and pathogens which will be illustrated in detail. The in vivo uses of CuS nanoparticles have also been investigated in preclinical studies, including molecular imaging with various techniques, cancer therapy based on the photothermal properties of CuS, as well as drug delivery and theranostic applications. Research on CuS nanoparticles will continue to thrive over the next decade, and tremendous opportunities lie ahead for potential biomedical/clinical applications of CuS nanoparticles., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)