Accurate diagnosis and precise and effective treatment are currently the two magic weapons for dealing with cancer. However, a single marker is often associated with multiple cellular events, which is not conducive to accurate diagnosis, and overly mild treatment methods often make the treatment effect unsatisfactory. In this paper, we construct a Au/Pd octopus nanoparticle–DNA nanomachine (Au/Pd ONP–DNA nanomachine) as a fully automatic diagnosis and treatment logic system. In this system, multiple DNA components are targeting detection units, Au/Pd ONPs act as carriers, and Au/Pd ONPs with an 808 nm laser is the treatment unit. In order to achieve the purpose of precise treatment, we will detect two secondary markers under the premise of detecting one major tumor marker. When all of the designated targets are detected (the logic system input is (1, 1, 1), and the output is (1, 1)), the 808 nm laser can be programmed to automatically radiate tumors and perform photothermal therapy and photodynamic therapy. In vivo and in vitro experiments show that this logic system not only can accurately identify tumor cells but also has considerable therapeutic effects.
Hydrogen therapy, an emerging therapeutic strategy, has recently attracted much attention in anticancer medicine. Evidence suggests that hydrogen (H2) can selectively reduce intratumoral overexpressed hydroxyl radicals (•OH) to break the redox homeostasis and thereby lead to redox stress and cell damage. However, the inability to achieve stable hydrogen storage and efficient hydrogen delivery hinders the development of hydrogen therapy. Furthermore, oxygen (O2) deficiency in the tumor microenvironment (TME) and the electron–hole separation inefficiency in photosensitizers have severely limited the efficacy of photodynamic therapy (PDT). Herein, a smart PdH@MnO2/Ce6@HA (PHMCH) yolk–shell nanoplatform is designed to surmount these challenges. PdH tetrahedrons combine stable hydrogen storage and high photothermal conversion efficiency of palladium (Pd) nanomaterials with near-infrared-controlled hydrogen release. Subsequently, the narrow bandgap semiconductor manganese dioxide (MnO2) and the photosensitizer chlorin e6 (Ce6) are introduced into the PHMCH nanoplatform. Upon irradiation, the staggered energy band edges in heterogeneous materials composed of MnO2 and Ce6 can efficiently facilitate electron–hole separation for increasing singlet oxygen (1O2). Moreover, MnO2 nanoshells generate O2 in TME for ameliorating hypoxia and further improving O2-dependent PDT. Finally, the hyaluronic acid-modified PHMCH nanoplatform shows negligible cytotoxicity and selectively targets CD44-overexpressing melanoma cells. The synergistic antitumor performance of the H2-mediated gas therapy combined with photothermal and enhanced PDT can explore more possibilities for the design of gas-mediated cancer therapy.
Integrating biological detection and treatment into one system is a smart therapeutic maneuver for efficient cancer treatment. Herein, a target‐activated core–satellite nanostructure (CS nanostructure) assembly built on gold nanobipyramids motor (AuNBPs motor)/gold nanoparticle probe (AuNP probe) exhibiting simultaneous dual signal‐on imaging, quantification of intracellular microRNA‐21 (miR‐21), and photothermal therapy (PTT) for cancer is designed. Of note, when the AuNBPs motor/AuNP probe enters into cells, miR‐21 triggers the reaction between AuNBPs motor and AuNP probe, resulting in the formation of CS nanostructure assembly. The process of assembling the CS nanostructure is accompanied with strong fluorescent signals from TAMRA and surface‐enhanced Raman scattering (SERS) signals from adenine. The fluorescent signal is leveraged to image the intracellular miR‐21 level, whereas the SERS signal is utilized for absolute quantification of intracellular miR‐21, and the CS nanostructure acts as the photosensitizer for PTT. This strategy can successfully image and quantify miR‐21 in a single cell, and also distinguish normal cells from tumor cells. Moreover, under the guidance of fluorescence signal, the assembly kills tumor cells and inhibits tumor growth via PTT. In vitro and in vivo results prove that the proposed strategy possesses enormous potential for application in the diagnosis and treatment of cancer.
Compared with the single-marker detection scheme, the detection of multiple targets in the complex cell and biological environment can obtain more reliable detection results. Herein, we detected miRNA-21 and APE1 in two modes, AND and OR, respectively, based on gold nanoflares and simple logic components. In both modes, DNAzyme and APE1 can get rich fluorescence recovery results by breaking the DNA strands from the gold nanorods (AuNRs) and unquenching under different conditions. In vivo and in vitro experiments suggest that both nanoflares exhibit excellent biocompatibility and make efficient and sensitive judgments on the two targets. This strategy emphasizes the reuse nature of enzymes, and a small amount of target can generate a large amount of fluorescent signal in the logic device, which greatly reduces the detection limit when monitoring low-abundance targets. Since the short-stranded DNA component of the detection device is simple in composition and easy to program its probe sequence, it can be expanded into a detection system for the detection of other sets of related markers, which increases its potential for clinical application.
Superfluous zinc ion (Zn 2+ ) in living cells has been identified as a potential tumor biomarker for early cancer diagnosis and cancer progression monitoring. In this paper, we developed a novel carbon nanohorns/Pt nanoparticles/ DNA (CNHs/Pt NPs/DNA) nanoplatform based on the clamped hybridization chain reaction (c-HCR) process for intracellular Zn 2+ imaging and enhanced cooperative phototherapy of cancer cells. Cross-shaped DNAzyme (c-DNAzyme), hairpin DNA1, hairpin DNA2, and aptamer DNA were adsorbed onto the surfaces of CNHs/Pt NPs, and the fluorescence of carboxytetramethyl-rhodamine was also quenched. After entering the living cells, the c-DNAzyme was cleaved to output trigger DNA in the existence of intracellular Zn 2+ and initiate the c-HCR process for fluorescence amplification. Compared with the single HCR process triggered by a single DNAzyme, the c-HCR process could further improve the amplification efficiency and sensitivity. In addition, such a nanoprobe possesses a catalysisenhanced photodynamic effect by Pt NP generation of oxygen in a tumor microenvironment and increases the photothermal effect by loading of Pt NPs on CNHs, indicating that this is a promising biological method for cancer diagnosis and cancer cell therapy.
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