A Bioactive Disintegrable Polymer Nanoparticle for Synergistic Vascular Anticalcification.

Although poly(aspartic acid) (PASP), a strong calcium chelating agent, may be potentially effective in inhibition of vascular calcification, its direct administration may lead to side effects. In this study, we employed polysuccinimide, a precursor of PASP, to prepare targeted polysuccinimide-based nanoparticles (PSI NPs) that not only acted as a prodrug but also functioned as a carrier of additional therapeutics to provide powerful synergistic vascular anticalcification effect. This paper shows that chemically modified PSI-NPs can serve as effective nanocarriers for loading of hydrophobic drugs, in addition to anticalcification and antireactive oxygen species (anti-ROS) activities. Curcumin (Cur), with high loading efficiency, was encapsulated into the NPs. The NPs were stable for 16 h in physiological conditions and then slowly dissolved/hydrolyzed to release the therapeutic PASP and the encapsulated drug. The drug release profile was found to be in good agreement with the NP dissolution profile such that complete release occurred after 48 h at physiological conditions. However, under acidic conditions, the NPs were stable, and Cur cumulative release reached only 30% after 1 week. Though highly effective in the prevention of calcium deposition, PSI NPs could not prevent the osteogenic trans-differentiation of vascular smooth muscle cells (VSMCs). The presence of Cur addressed this problem. It not only further reduced ROS level in macrophages but also prevented osteogenic differentiation of VSMCs in vitro. The NPs were examined in vivo in a rat model of vascular calcification induced by kidney failure through an adenine diet. The inclusion of Cur and PSI NPs combined the therapeutic effects of both. Cur-loaded NPs significantly reduced calcium deposition in the aorta without adversely affecting bone integrity or noticeable side effects/toxicity as examined by organ histological and serum biochemistry analyses.

Poly(succinimide) nanoparticles as reservoirs for spontaneous and sustained synthesis of poly(aspartic acid) under physiological conditions: potential for vascular calcification therapy and oral drug delivery.

This paper describes the preparation of poly(succinimide) nanoparticles (PSI NPs) and investigates their properties and characteristics. Employing direct and inverse precipitation methods, stable PSI NPs with tunable size and narrow dispersity were prepared without the use of any stabilizer or emulsifier. It was demonstrated that PSI NPs convert to poly(aspartic acid) (PASP) gradually under physiological conditions (37 °C, pH 7.4), while remaining stable under mildly acidic conditions. The dissolution profile was tuned and delayed by chemical modification of PSI. Through grafting a fluorophore to the PSI backbone, it was also demonstrated that such a spontaneous conversion could offer great potential for oral delivery of therapeutic agents to the colon. Sustained PASP synthesis also contributed to a sustained reduction of reactive oxygen species induced by iron. Furthermore, PSI NPs effectively prevented in vitro calcification of smooth muscle cells. This was attributed to the chelation of calcium ions to PASP, thereby inhibiting calcium deposition, because under cell culture conditions PSI NPs serve as reservoirs for the sustained synthesis of PASP. Overall, this study sheds light on the preparation and features of biocompatible and biodegradable PSI-based NPs and paves the way for further research to discover as-yet unfulfilled potential of this polymer in the form of nanoparticles.

Utilizing PET and MALDI Imaging for Discovery of a Targeted Probe for Brain Endocannabinoid α/ß-Hydrolase Domain 6 (ABHD6).

Multimodal imaging provides rich biological information, which can be exploited to study drug activity, disease associated phenotypes, and pharmacological responses. Here we show discovery and validation of a new probe targeting the endocannabinoid α/ß-hydrolase domain 6 (ABHD6) enzyme by utilizing positron emission tomography (PET) and matrix-assisted laser desorption/ionization (MALDI) imaging. [18F]JZP-MA-11 as the first PET ligand for in vivo imaging of the ABHD6 is reported and specific uptake in ABHD6-rich peripheral tissues and major brain regions was demonstrated using PET. A proof-of-concept study in nonhuman primate confirmed brain uptake. In vivo pharmacological response upon ABHD6 inhibition was observed by MALDI imaging. These synergistic imaging efforts used to identify biological information cannot be obtained by a single imaging modality and hold promise for improving the understanding of ABHD6-mediated endocannabinoid metabolism in peripheral and central nervous system disorders.

Metal ion chelation of poly(aspartic acid): From scale inhibition to therapeutic potentials.

Poly(aspartic acid) (PASP) is a biodegradable, biocompatible water-soluble synthetic anionic polypeptide. PASP has shown a strong affinity and thus robust complexation with heavy and alkaline earth metal ions, from which several applications are currently benefiting, and several more could also originate. This paper discusses different areas where the ion chelation ability of PASP has thus far been exploited. Due to its calcium chelation ability, PASP prevents precipitation of calcium salts and hence is widely used as an effective scale inhibitor in industry. Due to potassium chelation, PASP prevents precipitation of potassium tartrate and is employed as an efficient and edible stabilizer for wine preservation. Due to iron chelation, PASP inhibits corrosion of steel surfaces in harsh environments. Due to chelation, PASP can also enhance stability of various colloidal systems that contain metal ions. The chelation ability of PASP alleviated the toxicity of heavy metals in Zebrafish, inhibited the formation of kidney stones and dissolved calcium phosphate which is the main mineral of the calcified vasculature. These findings and beyond, along with the biocompatibility and biodegradability of the polymer could direct future investigations towards chelation therapy by PASP and other novel and undiscovered areas where metal ions play a key role.

Macroscale superlubricity induced by film-forming polymer brush-grafted colloidal additives.

HYPOTHESIS: Modifying surfaces with concentrated polymer brushes (CPBs) is an effective way to reduce friction of tribo-pairs lubricated with liquids. We investigate the hypothesis that colloids grafted with CPBs (hybrid colloids) can deposit onto tribo-substrates by varying the solvent quality with respect to the polymer, in order to obtain ultra-low coefficients of friction (CoFs), so-called superlubricity. EXPERIMENTS: Hybrid colloids are synthesized and characterized, and a dynamic light scattering compares their swellings in aqueous solutions of glycerol or polyethylene glycol. A mini-traction machine with viscoelastic tribo-pairs is used for lubrication experiments. Adsorption of colloids and film structures are tested using a quartz crystal microbalance and an atomic force microscope. FINDINGS: The solvent controls whether hybrid colloids spontaneously adsorb to the substrate under quiescent conditions or require contact forces to enable (tribo-)deposition. In both cases, the friction in the boundary-mixed lubrication regimes is lower upon increasing the degree of swelling of CPBs and upon increasing coverage of deposited colloids. The greatest lubrication enhancement and surface coverage occur for the spontaneously adsorbed colloids, with ultra-low CoFs of order 10-3 over a large range of speeds. The results demonstrate the potential for hybrid colloids to be used as solvent dispersible "friction modifier additives".

Investigation of a Dual siRNA/Chemotherapy Delivery System for Breast Cancer Therapy.

Multidrug resistance (MDR) is a problem that is often associated with a poor clinical outcome in chemotherapeutic cancer treatment. MDR may potentially be overcome by utilizing synergistic approaches, such as combining siRNA gene therapy and chemotherapy to target different mechanisms of apoptosis. In this study, a strategy is presented for developing multicomponent nanomedicines using orthogonal and compatible chemistries that lead to effective nanotherapeutics. Hyperbranched polymers were used as drug carriers that contained doxorubicin (DOX), attached via a pH-sensitive hydrazone linkage, and ataxia-telangiectasia mutated (ATM) siRNA, attached via a redox-sensitive disulfide group. This nanomedicine also contained cyanine 5 (Cy5) as a diagnostic tracer as well as in-house developed bispecific antibodies that allowed targeting of the epidermal growth factor receptor (EGFR) present on tumor tissue. Highly efficient coupling of siRNA was achieved with 80% of thiol end-groups on the hyperbranched polymer coupling with siRNA. This attachment was reversible, with the majority of siRNA released in vitro under reducing conditions as desired. In cellular studies, the nanomedicine exhibited increased DNA damage and cancer cell inhibition compared to the individual treatments. Moreover, the nanomedicine has great potential to suppress the metabolism of cancer cells including both mitochondrial respiration and glycolytic activity, with enhanced efficacy observed when targeted to the cell surface protein EGFR. Our findings indicated that co-delivery of ATM siRNA and DOX serves as a more efficient therapeutic avenue in cancer treatment than delivery of the single species and offers a potential route for synergistically enhanced gene therapy.

Poly(aspartic acid) in Biomedical Applications: From Polymerization, Modification, Properties, Degradation, and Biocompatibility to Applications.

Poly(aspartic acid) (PASP) is an anionic polypeptide that is a highly versatile, biocompatible, and biodegradable polymer that fulfils key requirements for use in a wide variety of biomedical applications. The derivatives of PASP can be readily tailored via the amine-reactive precursor, poly(succinimide) (PSI), which opens up a large window of opportunity for the design and development of novel biomaterials. PASP also has a strong affinity with calcium ions, resulting in complexation, which has been exploited for bone targeting and biomineralization. In addition, recent studies have further verified the biocompatibility and biodegradability of PASP-based polymers, which is attributed to their protein-like structure. In light of growing interest in PASP and its derivatives, this paper presents a comprehensive review on their synthesis, characterization, modification, biodegradation, biocompatibility, and applications in biomedical areas.

Diagnostic prospects and preclinical development of optical technologies using gold nanostructure contrast agents to boost endogenous tissue contrast.

Numerous developments in optical biomedical imaging research utilizing gold nanostructures as contrast agents have advanced beyond basic research towards demonstrating potential as diagnostic tools; some of which are translating into clinical applications. Recent advances in optics, lasers and detection instrumentation along with the extensive, yet developing, knowledge-base in tailoring the optical properties of gold nanostructures has significantly improved the prospect of near-infrared (NIR) optical detection technologies. Of particular interest are optical coherence tomography (OCT), photoacoustic imaging (PAI), multispectral optoacoustic tomography (MSOT), Raman spectroscopy (RS) and surface enhanced spatially offset Raman spectroscopy (SESORS), due to their respective advancements. Here we discuss recent technological developments, as well as provide a prediction of their potential to impact on clinical diagnostics. A brief summary of each techniques' capability to distinguish abnormal (disease sites) from normal tissues, using endogenous signals alone is presented. We then elaborate on the use of exogenous gold nanostructures as contrast agents providing enhanced performance in the above-mentioned techniques. Finally, we consider the potential of these approaches to further catalyse advances in pre-clinical and clinical optical diagnostic technologies.

Hydrogels Based on Poly(aspartic acid): Synthesis and Applications.

This review presents an overview on the recent progress in the synthesis, crosslinking, interpenetrating networks, and applications of poly(aspartic acid) (PASP)-based hydrogels. PASP is a synthetic acidic polypeptide that has drawn a great deal of attention in diverse applications due particularly to its biocompatibility and biodegradability. Facile modification of its precursor, poly(succinimide) (PSI), by primary amines has opened a wide window for the design of state-of-the-art hydrogels. Apart from pH-sensitivity, PASP hydrogels can be modified with suitable species in order to respond to the other desired stimuli such as temperature and reducing/oxidizing media as well. Strategies for fabrication of nanostructured PASP-based hydrogels in the form of particle and fiber are also discussed. Different cross-linking agents for PSI/PASP such as diamines, dopamine, cysteamine, and aminosilanes are also introduced. Finally, applications of PASP-based hydrogels in diverse areas particularly in biomedical are reviewed.

Ultrasound-triggered release from metal shell microcapsules.

Metal shell microcapsules have been shown to completely retain their core until its release is triggered, making them a promising candidate for use as a controllable drug delivery vehicle due to their superior retention properties as compared to polymer shell microcapsules. Focused ultrasound (FUS) has been successfully utilised to trigger release of lipophilic drugs from polymer microcapsules, and in this work the response of gold shell microcapsules with and without an inner polymeric shell, to FUS and standard ultrasound is explored. The results show that gold shell microcapsules with an inner polymer shell rupture when exposed to standard ultrasound and that there is a linear correlation between the gold shell thickness and the extent of shell rupture. When FUS is applied to these microcapsules, powers as low as 0.16 W delivered in bursts of 10 ms/s over a period of 120 s are sufficient to cause rupture of 53 nm gold shell microcapsules. Additional findings suggest that gold shell microcapsules without the polymer layer dispersed in a hydrogel matrix, as opposed to aqueous media, rupture more efficiently when exposed to FUS, and that thicker gold shells are more responsive to ultrasound-triggered rupture regardless of the external environment. Release of dye from all successfully ruptured capsules was sustained over a period of between 7 and 35 days. These findings suggest that emulsion-templated gold shell microcapsules embedded in a hydrogel matrix would be suitable for use as an implantable drug delivery vehicle with FUS used to externally trigger release.

Tagged Core-Satellite Nanoassemblies: Role of Assembling Sequence on Surface-Enhanced Raman Scattering (SERS) Performance.

Plasmonic nanoassemblies with amplified optical responses are attractive as chemo/bio sensors and diagnostic tracking agents. For real-life implementation, such nanostructures require a well-designed and controlled formation for maximizing the optical amplification. Forming these nanoassemblies typically requires numerous steps; however, the importance of the sequence of the steps is typically not discussed. Thus, here we have investigated the role of the sequence of tagging (or labeling, barcoding) of such plasmonic nanoassemblies with Raman active molecules in a quest to maximize the surface-enhanced Raman scattering (SERS) enhancement that could be achieved from the nanoassemblies. We have chosen the core-satellite nanoassembly arrangement to study the role of tagging sequence because it allows us to keep structural parameters constant that would otherwise influence the SERS amplification. We demonstrate that incorporating the tag molecule at an assembly point before formation of the nanojunctions leads to more tag molecules being positioned at the core-satellite nanojunctions, thereby resulting in higher SERS signal enhancement. This will thus prove to be a useful tool in fully utilizing the nanoassembly morphology generated hot-spot and maximizing its SERS performance.

Spatial arrangement of block copolymer nanopatterns using a photoactive homopolymer substrate.

Spatial control of the orientation of block copolymers (BCPs) in thin films offers enormous opportunities for practical nanolithography applications. In this study, we demonstrate the use of a substrate comprised of poly(4-acetoxystyrene) to spatially control interfacial interactions and block copolymer orientation over different length scales. Upon UV irradiation poly(4-acetoxystyrene) undergoes a photo-Fries rearrangement yielding phenolic groups available for further functionalization. The wetting behaviour of PS-b-PMMA deposited on the poly(4-acetoxystyrene) films could be precisely controlled through controlling the UV irradiation dose. After exposure, and a mild post-exposure treatment, the substrate switches from asymmetric, to neutral and then to symmetric wetting. Upon exposure through photomasks, a range of high fidelity micro-patterns consisting of perpendicularly oriented lamellar microdomains were generated. Furthermore, the resolution of chemically patterned poly(4-acetoxystyrene) substrate could be further narrowed to submicrometer scale using electron beam lithography. When the BCP was annealed on an e-beam modified poly(4-acetoxystyrene) surface, the interface between domains of parallel and perpendicular orientation of the BCPs was well defined, especially when compared with the substrates patterned using the photomask.

In vivo therapeutic evaluation of polymeric nanomedicines: effect of different targeting peptides on therapeutic efficacy against breast cancer.

Targeted nanomedicines offer many advantages over macromolecular therapeutics that rely only on passive accumulation within the tumour environment. The aim of this work was to investigate the in vivo anticancer efficiency of polymeric nanomedicines that were conjugated with peptide aptamers that show high affinity for receptors on many cancer cells. In order to assess the ability for the nanomedicine to treat cancer and investigate how structure affected the behavior of the nanomedicine, three imaging modalities were utilized, including in vivo optical imaging, multispectral optoacoustic tomography (MSOT) and ex vivo confocal microscopy. An 8-mer (A8) or 13-mer (A13) peptide aptamer that have been shown to exhibit high affinity for heat shock protein 70 (HSP70) was covalently-bound to hyperbranched polymer (HBP) nanoparticles with the purpose of both cellular targeting, as well as the potential to impart some level of chemo-sensitization to the cells. Furthermore, doxorubicin was bound to the polymeric carrier as the anticancer drug, and Cyanine-5.5 (Cy5.5) was incorporated into the polymer as a monomeric fluorophore to aid in monitoring the behavior of the nanomedicine. Enhanced tumour regression was observed in nude mice bearing MDA-MB-468 xenografts when the nanocarriers were targeted using the peptide ligands, compared to control groups treated with free DOX or HBP without aptamer. The accumulated DOX level in solid tumours was 5.5 times higher in mice treated with the targeted therapeutic, than mice treated with free DOX, and 2.6 times higher than the untargeted nanomedicine that relied only on passive accumulation. The results suggest that aptamer-targeted therapeutics have great potential for improving accumulation of nanomedicines in tumours for therapy.

3D shape change of multi-responsive hydrogels based on a light-programmed gradient in volume phase transition.

We present a new multi-responsive hydrogel based on oligo(ethylene glycol) methacrylate (OEGMA) and incorporating the photosensitive monomer 4-acetoxystyrene (AOST). Light irradiation creates a gradient in the volume phase transition temperature (VPTT) across the hydrogel, resulting in stimuli-responsive 3D deformations, with a largest achievable bending angle of 354°. The gradient hydrogels exhibited controllable, reversible and repeatable 3D deformations driven by changes in temperature or ionic strength. Multiple complex shape changes were achieved through patterned illumination.

A two-step synthesis for preparing metal microcapsules with a biodegradable polymer substrate.

Metal microcapsules have recently received attention and are being developed as improved carrier materials when compared to polymer microcapsules. In this work we have developed a novel, simplified method by which polymeric microcapsules can be synthesised using a combination of poly(vinyl pyrrolidone)-stabilised platinum nanoparticles (PVP-Pt) and poly(vinyl pyrrolidone) (PVP) as stabilisers, to allow for a secondary metal shell to be grown. We investigate the relationship between the molar ratio of reducing agent to platinum salt and the size of the resulting NPs and seek to develop further fundamental understanding of the factors governing the secondary metal shell thickness and quality, to allow production of cost-effective metal microcapsules without sacrificing core retention efficiency. We found that the size of the nanoparticles had no significant effect on secondary shell thickness, but did affect the quality of the resulting gold shells. Gold salt concentration was found to be a limiting factor in the electroless deposition of the metal shell. In this work, we have successfully produced PLGA microcapsules with more cost-effective gold shells, as thin as 56 ± 13 nm and capable of complete core retention of volatile actives.

Proton-Conducting La-Doped Ceria-Based Internal Reforming Layer for Direct Methane Solid Oxide Fuel Cells.

Performance degradation caused by carbon deposition substantially restricts the development of direct methane solid oxide fuel cells (SOFCs). Here, an internal reforming layer composed of Ni supported on proton conducting La-doped ceria, such as La2Ce2O7 (LDC) and La1.95Sm0.05Ce2O7 (LSDC) is applied over conventional Ni-Ce0.8Sm0.2O2-x (SDC) anodes for direct methane SOFCs. The proton conducting layer can adsorb water for internal reforming thus significantly improving the performance of the direct methane SOFCs. In situ Raman and FTIR results confirm the water adsorption capacity of LDC and LSDC. They also exhibit excellent phase stability in wet CO2 at 650 °C for 10 h, which ensures that the additional catalyst layer maintains structure stability during the internal reforming. In wet methane at 650 °C, the peak power density of the conventional cell is only 580 ± 20 mW cm-2, and increases to 699 ± 20 and 639 ± 20 mW cm-2 with the addition of Ni-LDC and -LSDC layers, respectively. For the stability test in wet methane at 650 °C and 0.2 A cm-2, the voltage of the conventional cell starts to drop dramatically in 10 h, while the Ni-LDC and -LSDC catalyst layers operate stably in 26 h under the identical conditions. These catalyst layers even show comparable stability in dry and wet methane in 26 h, but for longer operation, the wet methane is still preferred for maintaining the stability of the cell.

Using Peptide Aptamer Targeted Polymers as a Model Nanomedicine for Investigating Drug Distribution in Cancer Nanotheranostics.

Theranostics is a strategy that combines multiple functions such as targeting, stimulus-responsive drug release, and diagnostic imaging into a single platform, often with the aim of developing personalized medicine.1,2 Based on this concept, several well-established hyperbranched polymeric theranostic nanoparticles were synthesized and characterized as model nanomedicines to investigate how their properties affect the distribution of loaded drugs at both the cell and whole animal levels. An 8-mer peptide aptamer was covalently bound to the periphery of the nanoparticles to achieve both targeting and potential chemosensitization functionality against heat shock protein 70 (Hsp70). Doxorubicin was also bound to the polymeric carrier as a model chemotherapeutic drug through a degradable hydrazone bond, enabling pH-controlled release under the mildly acid conditions that are found in the intracellular compartments of tumor cells. In order to track the nanoparticles, cyanine-5 (Cy5) was incorporated into the polymer as an optical imaging agent. In vitro cellular uptake was assessed for the hyperbranched polymer containing both doxorubicin (DOX) and Hsp70 targeted peptide aptamer in live MDA-MB-468 cells, and was found to be greater than that of either the untargeted, DOX-loaded polymer or polymer alone due to the specific affinity of the peptide aptamer for the breast cancer cells. This was also validated in vivo with the targeted polymers showing much higher accumulation within the tumor 48 h postinjection than the untargeted analogue. More detailed assessment of the nanomedicine distribution was achieved by directly following the polymeric carrier and the doxorubicin at both the in vitro cellular level via compartmental analysis of confocal images of live cells and in whole tumors ex vivo using confocal imaging to visualize the distribution of the drug in tumor tissue as a function of distance from blood vessels. Our results indicate that this polymeric carrier shows promise as a cancer theranostic, demonstrating active targeting to tumor cells with the capability for simultaneous drug release.

Hydrogels with Lotus Leaf Topography: Investigating Surface Properties and Cell Adhesion.

The interactions of cells with the surface of materials is known to be influenced by a range of factors that include chemistry and roughness; however, it is often difficult to probe these factors individually without also changing the others. Here we investigate the role of roughness on cell adhesion while maintaining the same underlying chemistry. This was achieved by using a polymerization in mold technique to prepare poly(hydroxymethyl methacrylate) hydrogels with either a flat topography or a topography that replicated the microscale features of lotus leaves. These materials were then assessed for cell adhesion, and atomic force microscopy and contact angle analysis were then used to probe the physical reasons for the differing behavior in relation to cell adhesion.

Hyperbranched polymer-gold nanoparticle assemblies: role of polymer architecture in hybrid assembly formation and SERS activity.

Plasmonic gold nanoassemblies that self-assemble with the aid of linking molecules or polymers have the potential to yield controlled hierarchies of morphologies and consequently result in materials with tailored optical (e.g., localized surface plasmon resonances (LSPR)) and spectroscopic properties (e.g., surface-enhanced Raman scattering (SERS)). Molecular linkers that are structurally well-defined are promising for forming hybrid nanoassemblies which are stable in aqueous solution and are increasingly finding application in nanomedicine. Despite much ongoing research in this field, the precise role of molecular linkers in governing the morphology and properties of the hybrid nanoassemblies remains unclear. Previously we have demonstrated that branched linkers, such as hyperbranched polymers, with specific anchoring end groups can be successfully employed to form assemblies of gold NPs demonstrating near-infrared SPRs and intense SERS scattering. We herein introduce a tailored polymer as a versatile molecular linker, capable of manipulating nanoassembly morphologies and hot-spot density. In addition, this report explores the role of the polymeric linker architecture, specifically the degree of branching of the tailored polymer in determining the formation, morphology, and properties of the hybrid nanoassemblies. The degree of branching of the linker polymer, in addition to the concentration and number of anchoring groups, is observed to strongly influence the self-assembly process. The assembly morphology shifts primarily from 1D-like chains to 2D plates and finally to 3D-like globular structures, with increase in degree of branching of the macromolecular linker. Insights have been gained into how the morphology influences the SERS performance of these nanoassemblies with respect to hot-spot density. These findings supplement the understanding of the morphology determining nanoassembly formation and pave the way for the possible application of these nanoassemblies as SERS biosensors for medical diagnostics.

Multimodal polymer nanoparticles with combined 19F magnetic resonance and optical detection for tunable, targeted, multimodal imaging in vivo.

Understanding the complex nature of diseased tissue in vivo requires development of more advanced nanomedicines, where synthesis of multifunctional polymers combines imaging multimodality with a biocompatible, tunable, and functional nanomaterial carrier. Here we describe the development of polymeric nanoparticles for multimodal imaging of disease states in vivo. The nanoparticle design utilizes the abundant functionality and tunable physicochemical properties of synthetically robust polymeric systems to facilitate targeted imaging of tumors in mice. For the first time, high-resolution (19)F/(1)H magnetic resonance imaging is combined with sensitive and versatile fluorescence imaging in a polymeric material for in vivo detection of tumors. We highlight how control over the chemistry during synthesis allows manipulation of nanoparticle size and function and can lead to very high targeting efficiency to B16 melanoma cells, both in vitro and in vivo. Importantly, the combination of imaging modalities within a polymeric nanoparticle provides information on the tumor mass across various size scales in vivo, from millimeters down to tens of micrometers.