Cellular-membrane-coated nanoparticles have increasingly been pursued to leverage the natural cell functions for enhancing biocompatibility and improved therapeutic efficacy. Taking advantage of specialized cell membranes or combining functions from different membrane types facilitates the strengthening of their functionality. Herein, we fuse membrane materials derived from red blood cells (RBCs) and melanoma cells (B16-F10 cells) to create a hybrid biomimetic coating (RBC-B16), and RBC-B16 hybrid membrane camouflaged doxorubicin (DOX)-loaded hollow copper sulfide nanoparticles (DCuS@[RBC-B16] NPs) are fabricated for combination therapy of melanoma. The DCuS@[RBC-B16] NPs are comprehensively characterized, showing the inherent properties of the both source cells. Compared to the bare CuS NPs, the DCuS@[RBC-B16] NPs exhibit highly specific self-recognition to the source cell line in vitro and achieve markedly prolonged circulation lifetime and enhanced homogeneous targeting abilities in vivo inherited from the source cells. Thus, the DOX-loaded [RBC-B16]-coated CuS NP platform exhibits excellent synergistic photothermal/chemotherapy with about 100% melanoma tumor growth inhibition rate. The reported strategy may contribute to personalized nanomedicine of various tumors by combining the RBCs with a homotypic cancer membrane accordingly on the surface of the nanoparticle.
The therapeutic effect of reactive oxygen species (ROS)-involved cancer therapies is significantly limited by shortage of oxy-substrates, such as hypoxia in photodynamic therapy (PDT) and insufficient hydrogen peroxide (H 2 O 2 ) in chemodynamic therapy (CDT). Here, we report a H 2 O 2 /O 2 self-supplying nanoagent, (MSNs@CaO 2 -ICG)@LA, which consists of manganese silicate (MSN)-supported calcium peroxide (CaO 2 ) and indocyanine green (ICG) with further surface modification of phase-change material lauric acid (LA). Under laser irradiation, ICG simultaneously generates singlet oxygen and emits heat to melt the LA. The exposed CaO 2 reacts with water to produce O 2 and H 2 O 2 for hypoxia-relieved ICG-mediated PDT and H 2 O 2 -supplying MSN-based CDT, acting as an open source strategy for ROS production. Additionally, the MSNs-induced glutathione depletion protects ROS from scavenging, termed reduce expenditure. This open source and reduce expenditure strategy is effective in inhibiting tumor growth both in vitro and in vivo, and significantly improves ROS generation efficiency from multi-level for ROS-involved cancer therapies.
The limited penetration depth of photothermal agents (PTAs) active in the NIR-I biowindow and the thermoresistance caused by heat shock protein (HSP) significantly limit the therapeutic efficiency of photothermal therapy (PTT). To address the problem, we introduce a strategy of low-temperature nucleus-targeted PTT in the NIR-II region achieving effective tumor killing by combining the vanadium carbide quantum dots (V2C QDs) PTA and an engineered exosomes (Ex) vector. The small fluorescent V2C QDs with good photothermal effect in the NIR-II region were modified with TAT peptides and packaged into Ex with RGD modification (V2C-TAT@Ex-RGD). The resulting nanoparticles (NPs) exhibited good biocompatibility, long circulation time, and endosomal escape ability, and they could target the cell and enter into the nucleus to realize low-temperature PTT with advanced tumor destruction efficiency. The fluorescent imaging, photoacoustic imaging (PAI), and magnetic resonance imaging (MRI) capability of the NPs were also revealed. The low-temperature nucleus-targeted PTT in the NIR-II region provides more possibilities toward successful clinical application of PTT.
Small size molybdenum disulfide (MoS2) quantum dots (QDs) with desired optical properties were controllably synthesized by using tetrabutylammonium-assisted ultrasonication of multilayered MoS2 powder via OH-mediated chain-like Mo-S bond cleavage mode. The tunable up-bottom approach of precise fabrication of MoS2 QDs finally enables detailed experimental investigations of their optical properties. The synthesized MoS2 QDs present good down-conversion photoluminescence behaviors and exhibit remarkable up-conversion photoluminescence for bioimaging. The mechanism of the emerging photoluminescence was investigated. Furthermore, superior (1)O2 production ability of MoS2 QDs to commercial photosensitizer PpIX was demonstrated, which has great potential application for photodynamic therapy. These early affording results of tunable synthesis of MoS2 QDs with desired photo properties can lead to application in fields of biomedical and optoelectronics.
Porous metal–organic frameworks (MOFs) nanostructures constructed from metal ion/ion clusters and organic bridging ligands hold great promise for biomedicine applications. The developing of nanoagents achieving accurate diagnosis and improved therapeutic effect is highly desirable. Herein, a new‐style versatile zirconium‐ferriporphyrin metal–organic framework (Zr‐FeP MOF) nanoshuttles is reported using a facile one‐pot hydrothermal method. The Zr‐FeP MOF nanoshuttles enable simultaneously to generate abundant reactive oxygen species including hydroxyl radical (·OH) and singlet oxygen (1O2) under a near‐infrared (NIR) laser irradiation. Significant photothermal effect of Zr‐FeP MOF nanoshuttles with photothermal conversion efficiency high to 33.7% is also demonstrated. Under a single NIR laser irradiation, the Zr‐FeP MOF nanoshuttles loaded with heat shock protein 70 siRNA efficiently suppress the tumor growth both in vitro and in vivo owing to the synergistic effect of photodynamic therapy (PDT) and low‐temperature photothermal therapy (PTT). Meanwhile, it exhibits good photothermal imaging, computed tomography, and photoacoustic imaging tri‐mode tumor‐specific imaging capability for tumor accurate diagnosis. This work contributes to design “all‐in‐one” nanoagents that realize multimodal imaging diagnosis and PDT and low‐temperature PTT synergistic treatments.
Molybdenum disulfide (MoS2 ) quantum dots (QDs) (size <10 nm) possess attractive new properties due to the quantum confinement and edge effects as graphene QDs. However, the synthesis and application of MoS2 QDs has not been investigated in great detail. Here, a facile and efficient approach for synthesis of controllable-size MoS2 QDs with excellent photoluminescence (PL) by using a sulfuric acid-assisted ultrasonic route is developed for this investigation. Various MoS2 structures including monolayer MoS2 flake, nanoporous MoS2 , and MoS2 QDs can be yielded by simply controlling the ultrasonic durations. Comprehensive microscopic and spectroscopic tools demonstrate that the MoS2 QDs have uniform lateral size and possess excellent excitation-independent blue PL. The as-generated MoS2 QDs show high quantum yield of 9.65%, long fluorescence lifetime of 4.66 ns, and good fluorescent stability over broad pH values from 4 to 10. Given the good intrinsic optical properties and large surface area combined with excellent physiological stability and biocompatibility, a MoS2 QDs-based intracellular microRNA imaging analysis system is successfully constructed. Importantly, the MoS2 QDs show good performance as multiphoton bioimaging labeling. The proposed synthesis strategy paves a new way for facile and efficient preparing MoS2 QDs with tunable-size for biomedical imaging and optoelectronic devices application.
Multifunctional theranostic platform coupling diagnostic and therapeutic functions holds great promise for personalized nanomedicine. Nevertheless, integrating consistently high performance in one single agent is still challenging. This work synthesized a sort of porphyrin derivatives (P) with high singlet oxygen generation ability and graphene quantum dots (GQDs) possessing good fluorescence properties. The P was conjugated to polyethylene glycol (PEG)ylated and aptamer-functionalized GQDs to gain a multifunctional theranostic agent (GQD-PEG-P). The resulting GQD-PEG-P displayed good physiological stability, excellent biocompatibility and low cytotoxicity. The intrinsic fluorescence of the GQDs could be used to discriminate cancer cells from somatic cells, whereas the large surface facilitated gene delivery for intracellular cancer-related microRNA (miRNA) detection. Importantly, it displayed a photothermal conversion efficiency of 28.58% and a high quantum yield of singlet oxygen generation up to 1.08, which enabled it to accomplish advanced photothermal therapy (PTT) and efficient photodynamic therapy (PDT) for cancer treatment. The combined PTT/PDT synergic therapy led to an outstanding therapeutic efficiency for cancer cell treatment.
Sonodynamic therapy (SDT) has attracted much attention since it can break the depth-penetration barrier of phototriggered therapeutic strategies. However, developing sonosensitizers with a high reactive oxygen species (ROS) quantum yield for precision and enhanced SDT remains a major challenge. In this study, Au nanocrystals were selectively grew on the edge of the TiO2 nanosheets (NSs) with highly exposed (001) facets to fabricate Au-TiO2 NSs as sonosensitizers for enhanced SDT. The high sonosensitization efficiency was closely linked to the effective prevention of the fast recombination of excited electrons and holes. Under ultrasound (US) irradiation, the ROS generation efficiency of the resulting Au-TiO2 NSs was higher compared to pure TiO2 NSs and superior to previous TiO2 nanocomposite. The Au-TiO2 was further modified with mitochondria-targeted triphenylphosphine (TPP) and AS1411 aptamer (Au-TiO2-A-TPP) to realize organelle-targeted enhanced SDT and CT (computed tomography) imaging. The tumor growth inhibition was completely realized via Au-TiO2-A-TPP-mediated SDT both in vitro and in vivo due to the adequate ROS generation in the mitochondria organelle. This knowledge is vital to design an inorganic sonosensitizer with structure-dependent and mitochondria-target related SDT enhancement.
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