Extensive efforts have been devoted to synthesizing photothermal agents (PTAs) that are active in the first near-infrared (NIR) region (650–950 nm). However, PTAs for photothermal therapy in the ...second NIR window (1000–1350 nm) are still rare. Here, it is shown that two-dimensional ultrathin polypyrrole (PPy) nanosheets prepared via a novel space-confined synthesis method could exhibit unique broadband absorption with a large extinction coefficient of 27.8 L g–1 cm–1 at 1064 nm and can be used as an efficient PTA in the second NIR window. This unique optical property is attributed to the formation of bipolaron bands in highly doped PPy nanosheets. The measured prominent photothermal conversion efficiency could achieve 64.6%, surpassing previous PTAs that are active in the second NIR window. Both in vitro and in vivo studies reveal that these ultrathin PPy nanosheets possess good biocompatibility and notable tumor ablation ability in the second NIR window. Our study highlights the potential of ultrathin two-dimensional polymers with unique optical properties in biomedical applications.
Development of photothermal materials which are able to harness sunlight and convert it to thermal energy seems attractive. Besides carbon-based nanomaterials, conjugated polymers are emerging ...promising photothermal materials but their facile syntheses remain challenging. In this work, by modification of a CBT-Cys click condensation reaction and rational design of the starting materials, we facilely synthesize conjugated polymers poly-2-phenyl-benzobisthiazole (PPBBT) and its dihexyl derivative with good photothermal properties. Under the irradiation of either sunlight-mimicking Xe light or near-infrared laser, we verify that PPBBT has comparable photothermal heating-up speed to that of star material single-wall carbon nanotube. Moreover, PPBBT is used to fabricate water-soluble NP
nanoparticles which maintain excellent photothermal properties in vitro and photothermal therapy effect on the tumours exposed to laser irradiation. We envision that our synthetic method provides a facile approach to fabricate conjugated polymers for more promising applications in biomedicine or photovoltaics in the near future.
Stimuli‐responsive materials are so named because they can alter their physicochemical properties and/or structural conformations in response to specific stimuli. The stimuli can be internal, such as ...physiological or pathological variations in the target cells/tissues, or external, such as optical and ultrasound radiations. In recent years, these materials have gained increasing interest in biomedical applications due to their potential for spatially and temporally controlled release of theranostic agents in response to the specific stimuli. This article highlights several recent advances in the development of such materials, with a focus on their molecular designs and formulations. The future of stimuli‐responsive materials will also be explored, including combination with molecular imaging probes and targeting moieties, which could enable simultaneous diagnosis and treatment of a specific disease, as well as multi‐functionality and responsiveness to multiple stimuli, all important in overcoming intrinsic biological barriers and increasing clinical viability.
Stimuli‐responsive carriers can respond to environmental variations and release theranostic cargos in a spatially and temporally controlled manner. The variations can be internal, such as physiological and pathological changes in the target cells/tissues, or caused by external means such as optical and ultrasound radiations.
The efficacy of nano-mediated drug delivery has been impeded by multiple biological barriers such as the mononuclear phagocyte system (MPS), as well as vascular and interstitial barriers. To overcome ...the abovementioned obstacles, we report a nano-pathogenoid (NPN) system that can in situ hitchhike circulating neutrophils and supplement photothermal therapy (PTT). Cloaked with bacteria-secreted outer membrane vesicles inheriting pathogen-associated molecular patterns of native bacteria, NPNs are effectively recognized and internalized by neutrophils. The neutrophils migrate towards inflamed tumors, extravasate across the blood vessels, and penetrate through the tumors. Then NPNs are rapidly released from neutrophils in response to inflammatory stimuli and subsequently taken up by tumor cells to exert anticancer effects. Strikingly, due to the excellent targeting efficacy, cisplatin-loaded NPNs combined with PTT completely eradicate tumors in all treated mice. Such a nano-platform represents an efficient and generalizable strategy towards in situ cell hitchhiking as well as enhanced tumor targeted delivery.
Destruction for detection: Protein‐protected Au clusters are exploited as nanoscale sensors for label‐free fluorescence detection of proteases with high sensitivity. The detection mechanism is based ...on degradation of the protein shell by a protease, allowing the O2 from ambient air to penetrate through and quench the fluorescence from the Au cluster.
The coverage density of poly(ethylene glycol) (PEG) is a key parameter in determining the efficiency of PEGylation, a process pivotal to in vivo delivery and targeting of nanomaterials. Here we ...report four complementary methods for quantifying the coverage density of PEG chains on various types of Au nanostructures by using a model system based on HS–PEG–NH2 with different molecular weights. Specifically, the methods involve reactions with fluorescamine and ninhydrin, as well as labeling with fluorescein isothiocyanate (FITC) and Cu2+ ions. The first two methods use conventional amine assays to measure the number of unreacted HS–PEG–NH2 molecules left behind in the solution after incubation with the Au nanostructures. The other two methods involve coupling between the terminal −NH2 groups of adsorbed −S–PEG–NH2 chains and FITC or a ligand for Cu2+ ion, and thus pertain to the “active” −NH2 groups on the surface of a Au nanostructure. We found that the coverage density decreased as the length of PEG chains increased. A stronger binding affinity of the initial capping ligand to the Au surface tended to reduce the PEGylation efficiency by slowing down the ligand exchange process. For the Au nanostructures and capping ligands we have tested, the PEGylation efficiency decreased in the order of citrate-capped nanoparticles > PVP-capped nanocages ≈ CTAC-capped nanoparticles ≫ CTAB-capped nanorods, where PVP, CTAC, and CTAB stand for poly(vinyl pyrrolidone), cetyltrimethylammonium chloride, and cetyltrimethylammonium bromide, respectively.
The typical analysis on the effectiveness of soda taxes relies on price elasticity estimates from static demand models, which ignores consumers' inventory behaviors and their persistent tastes. This ...article provides estimates of the relevant price elasticities based on a dynamic demand model that better addresses potential intertemporal substitution and unobservable persistent heterogeneous tastes. It finds that static analyses overestimate the long-run own-price elasticity of regular soda by 60.8%, leading to overestimated consumption reduction of sugar-sweetened soft drinks by up to 57.9% in some cases. Results indicate that soda taxes will raise revenue but are unlikely to substantially impact soda consumption.
Gold nanohexapods represent a novel class of optically tunable nanostructures consisting of an octahedral core and six arms grown on its vertices. By controlling the length of the arms, their ...localized surface plasmon resonance peaks could be tuned from the visible to the near-infrared region for deep penetration of light into soft tissues. Herein we compare the in vitro and in vivo capabilities of Au nanohexapods as photothermal transducers for theranostic applications by benchmarking against those of Au nanorods and nanocages. While all these Au nanostructures could absorb and convert near-infrared light into heat, Au nanohexapods exhibited the highest cellular uptake and the lowest cytotoxicity in vitro for both the as-prepared and PEGylated nanostructures. In vivo pharmacokinetic studies showed that the PEGylated Au nanohexapods had significant blood circulation and tumor accumulation in a mouse breast cancer model. Following photothermal treatment, substantial heat was produced in situ and the tumor metabolism was greatly reduced for all these Au nanostructures, as determined with 18F-flourodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Combined together, we can conclude that Au nanohexapods are promising candidates for cancer theranostics in terms of both photothermal destruction and contrast-enhanced diagnosis.
A facile, robust approach to the synthesis of Au cubic nanoframes is described. The synthesis involves three major steps: 1) preparation of Au–Ag alloyed nanocages using a galvanic replacement ...reaction between Ag nanocubes and HAuCl4; 2) deposition of thin layers of pure Au onto the surfaces of the nanocages by reducing HAuCl4 with ascorbic acid, and; 3) formation of Au cubic nanoframes through a dealloying process with HAuCl4. The key to the formation of Au cubic nanoframes is to coat the surfaces of the Au–Ag nanocages with sufficiently thick layers of Au before they are dealloyed. The Au layer could prevent the skeleton of a nanocage from being fragmented during the dealloying step. The as‐prepared Au cubic nanoframes exhibit tunable localized surface plasmon resonance peaks in the near‐infrared region, but with much lower Ag content as compared with the initial Au–Ag nanocages.
Cubic nanoframes of Au are synthesized by integrating galvanic replacement with deposition of Au and dealloying of Ag. The as‐prepared cubic nanoframes exhibit tunable localized surface plasmon resonance peaks in the near‐infrared region, but with much lower Ag content as compared with the conventional Au–Ag nanocages.
Daratumumab is a human monoclonal antibody that targets CD38, a cell surface protein that is overexpressed on multiple myeloma (MM) cells. Preclinical studies have shown that daratumumab induces MM ...cell death through several mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and apoptosis. Given the encouraging efficacy and acceptable safety profile of daratumumab demonstrated in clinical trials, daratumumab has emerged as a novel treatment option for myeloma and became the first monoclonal antibody approved by the FDA for the treatment of MM.
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