Visible-Light-Activated Molecular Nanomachines Kill Pancreatic Cancer Cells

Recently, synthetic molecular nanomachines (MNMs) that rotate unidirectionally in response to UV light excitation have been used to produce nanomechanical action on live cells to kill them through the drilling of holes in their cell membranes. In the work here, visible-light-absorbing MNMs are designed and synthesized to enable nanomechanical activation by 405 nm light, thereby using a wavelength of light that is less phototoxic than the previously employed UV wavelengths. Visible-light-absorbing MNMs that kill pancreatic cancer cells upon response to light activation are demonstrated. Evidence is presented to support the conclusion that MNMs do not kill cancer cells by the photothermal effect when used at low optical density. In addition, MNMs suppress the formation of reactive oxygen species, leaving nanomechanical action as the most plausible working mechanism for cell killing under the experimental conditions

Sub-100 nm gold nanomatryoshkas improve photo-thermal therapy efficacy in large and highly aggressive triple negative breast tumors

There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or necrotic regions. We report the performance advantages obtained by sub 100 nm gold nanomatryushkas, comprising concentric gold–silica–gold layers compared to conventional ~ 150 nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica–core–gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (> 1000 mm3) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4–5 × accumulation within large tumors results in superior therapy efficacy

Indium-decorated Pd nanocubes degrade nitrate anions rapidly

Indium-decorated palladium nanoparticles (In-on-PdNPs) are active for room-temperature catalytic reduction of aqueous nitrate, where the active sites are metallic In atoms on the Pd surface. The PdNPs are pseudo-spherical in shape, and it is unclear if their faceted nature plays a role in nitrate reduction. We synthesized different-sized, cube-shaped NPs with differing In coverages (sc%), and studied the resultant In-on-Pd-nanocubes (NCs) for nitrate reduction. The NCs exhibited volcano-shape activity dependence on In sc%, with peak activity around 65–75 sc%. When rate constants were normalized to undercoordinated atoms (at edge + corners), the NCs exhibited near-identical maximum activity (20×-higher than In-on-PdNPs) at ρIn/Pd edge+corner ∼0.5 (∼5 In atoms per 10 edge and corner atoms). NCs with a higher In edge + corner density (ρIn/Pd edge+corner ∼1.5) were less active but did not generate NH4+ at nitrate conversions tested up to 36 %. Edge-decorated cubes may be the structural basis of improved bimetallic catalytic denitrification of water

Theranostic gold nanoshells and nanomatryoshkas for cancer therapy

This dissertation describes the synthesis of multifunctional gold nanoparticles designed for therapy and diagnosis of cancer (theranostics), and the evaluation of their therapeutic efficacy and bioimaging of tumors in mice. The design of these metallic nanoparticles is aimed to incorporate imaging agents (MRI contrasts and fluorophores) in compact structures with dimensions below 100 nm while keeping their NIR-light-absorbing properties and optimum surface chemistry to enhance accumulation in tumor. The therapeutic response of these metallic nanoparticles is derived from the photoexcitation of their plasmon resonance, the collective oscillation of the conduction band electrons, which was advantageously utilized to enhance the quantum yield of fluorophores resonant in the NIR where the penetration of light is maximal in biological tissue and minimally destructive. Gold nanoshells as absorbers of NIR light can convert the absorbed light into heat consequently causing hyperthermia in the surrounding medium which leads to tumor cell death. To extent the application of previously developed theranostic nanoshells to the highly lethal pancreatic cancer, chapter 2 describes a magneto-fluorescent theranostic nanocomplex targeted to neutrophil gelatinase associated lipocalin (NGAL) receptor in pancreatic cancer. Gold nanoshells (SiO2-Au core-shell nanoshell) resonant at 810 nm were encapsulated in silica epilayers doped with iron oxide and the NIR dye ICG, resulting in a theranostic gold nanoshells, which provided contrast for both T2 weighted MRI and NIR fluorescence optical imaging. The large size of this complex (200 nm) potentially can hinder the accumulation in tumor. Seeking to reduce the size of the theranostic nanoparticles, chapter 3 presents the sub-100 nm Au nanomatryoshkas (Au/SiO2/Au). Au nanomatryoshkas are strong light absorbers with 77% absorption efficiency while the nanoshells are weaker absorbers with only 15% absorption efficiency. After an intravenous injection of Au nanomatryoshkas followed by a single NIR laser dose of 2 W/cm2 for 5 min, 83% of the tumor-bearing mice appeared healthy and tumor free >60 days later, while only 40% of mice treated with nanoshells survived the same period. The smaller size and larger absorption cross section of Au nanomatryoshkas combine to make this nanoparticle more effective than Au nanoshells for photothermal cancer therapy. Chapter 4 presents the therapeutic efficacy in mice bearing large (>1000 mm3) and highly aggressive triple negative breast tumors. To equip the Au nanomatryoshkas with imaging contrast agents, fluorophores were encapsulated in the internal SiO2 layer of the Au/SiO2/Au matryoshkas as described in chapter 5. We observed strong fluorescence enhancements of the NIR dyes Cy7 and IR800. This behavior can be understood by taking into account the near field enhancement induced by the Fano resonance of the nanomatryoshka, which is responsible for enhanced absorption of the fluorophores incorporated into the nanocomplex. The combination of compact size and enhanced light emission with internal encapsulation of the fluorophores for increased biocompatibility suggests outstanding potential for this type of nanoparticle complex in biomedical applications as it is investigated and presented in chapter 6

Enhancing the photocurrent and photoluminescence of single crystal monolayer MoS2ﾠwith resonant plasmonic nanoshells

Monolayer molybdenum disulfide (MoS2) produced by controlled vapor-phase synthesis is a commercially promising new two-dimensional material for optoelectronics because of its direct bandgap and broad absorption in the visible and ultraviolet regimes. By tuning plasmonic core-shell nanoparticles to the direct bandgap of monolayer MoS2 and depositing them sparsely (<1% coverage) onto the material's surface, we observe a threefold increase in photocurrent and a doubling of photoluminescence signal for both excitonic transitions, amplifying but not altering the intrinsic spectral response

The Surprising in Vivo Instability of Near-IR-Absorbing Hollow Au-Ag Nanoshells

Photothermal ablation based on resonant illumination of near-infrared-absorbing noble metal nanoparticles that have accumulated in tumors is a highly promising cancer therapy, currently in multiple clinical trials. A crucial aspect of this therapy is the nanoparticle size for optimal tumor uptake. A class of nanoparticles known as hollow Au (or Au–Ag) nanoshells (HGNS) is appealing because near-IR resonances are achievable in this system with diameters less than 100 nm. However, in this study, we report a surprising finding that in vivo HGNS are unstable, fragmenting with the Au and the remnants of the sacrificial Ag core accumulating differently in various organs. We synthesized 43, 62, and 82 nm diameter HGNS through a galvanic replacement reaction, with nanoparticles of all sizes showing virtually identical NIR resonances at ∼800 nm. A theoretical model indicated that alloying, residual Ag in the nanoparticle core, nanoparticle porosity, and surface defects all contribute to the presence of the plasmon resonance at the observed wavelength, with the major contributing factor being the residual Ag. While PEG functionalization resulted in stable nanoparticles under laser irradiation in solution, an anomalous, strongly element-specific biodistribution observed in tumor-bearing mice suggests that an avid fragmentation of all three sizes of nanoparticles occurred in vivo. Stability studies across a wide range of pH environments and in serum confirmed HGNS fragmentation. These results show that NIR resonant HGNS contain residual Ag, which does not stay contained within the HGNS in vivo. This demonstrates the importance of tracking both materials of a galvanic replacement nanoparticle in biodistribution studies and of performing thorough nanoparticle stability studies prior to any intended in vivo trial application

Indium-decorated Pd nanocubes degrade nitrate anions rapidly

Indium-decorated palladium nanoparticles (In-on-PdNPs) are active for room-temperature catalytic reduction of aqueous nitrate, where the active sites are metallic In atoms on the Pd surface. The PdNPs are pseudo-spherical in shape, and it is unclear if their faceted nature plays a role in nitrate reduction. We synthesized different-sized, cube-shaped NPs with differing In coverages (sc%), and studied the resultant In-on-Pd-nanocubes (NCs) for nitrate reduction. The NCs exhibited volcano-shape activity dependence on In sc%, with peak activity around 65-75 sc%. When rate constants were normalized to undercoordinated atoms (at edge+corners), the NCs exhibited near-identical maximum activity (20×-higher than In-on-PdNPs) at ρIn/Pd edge+corner ~0.5 (~5 In atoms per 10 edge and corner atoms). NCs with a higher In edge+corner density (ρIn/Pd edge+corner ~1.5) were less active but did not generate NH4+ at nitrate conversions tested up to 36%. Edge-decorated cubes may be the structural basis of improved bimetallic catalytic denitrification of water

Nanoparticle-Mediated, Light-Induced Phase Separations

Nanoparticles that both absorb and scatter light, when dispersed in a liquid, absorb optical energy and heat a reduced fluid volume due to the combination of multiple scattering and optical absorption. This can induce a localized liquid–vapor phase change within the reduced volume without the requirement of heating the entire fluid. For binary liquid mixtures, this process results in vaporization of the more volatile component of the mixture. When subsequently condensed, these two steps of vaporization and condensation constitute a distillation process mediated by nanoparticles and driven by optical illumination. Because it does not require the heating of a large volume of fluid, this process requires substantially less energy than traditional distillation using thermal sources. We investigated nanoparticle-mediated, light-induced distillation of ethanol-H₂O and 1-propanol-H₂O mixtures, using Au–SiO₂ nanoshells as the absorber-scatterer nanoparticle and nanoparticle-resonant laser irradiation to drive the process. For ethanol-H₂O mixtures, the mole fraction of ethanol obtained in the light-induced process is substantially higher than that obtained by conventional thermal distillation, essentially removing the ethanol-H₂O azeotrope that limits conventional distillation. In contrast, for 1-propanol-H₂O mixtures the distillate properties resulting from light-induced distillation were very similar to those obtained by thermal distillation. In the 1-propanol-H₂O system, a nanoparticle-mediated, light-induced liquid–liquid phase separation was also observed