Engineering a versatile oncotherapy nanoplatform integrating both diagnostic and therapeutic functions has always been an intractable challenge in targeted cancer treatment. Herein, to actualize the theme of precise medicine, a nanoplatform is developed by anchoring Mn-Cdots to doxorubicin (DOX)-loaded mesoporous silica-coated gold cube-in-cubes core/shell nanocomposites and further conjugating them to a Arg-Gly-Asp (RGD) peptide (denoted as RGD-CCmMC/DOX) to achieve an active-targeting effect. Under 635 nm irradiation, the nanoplatform acts as oxygen nanogenerator that produces O2 in situ and amplifies the content of singlet oxygen (1O2) in the hypoxic tumor microenvironment (TME), which has been demonstrated to attenuate tumor hypoxia and synchronously enhance photodynamic efficacy. Moreover, the gold cube-in-cube core in this work has been proven as a photothermal agent for hyperthermia, which exhibits a favorable photothermal effect with a 65.6% calculated photothermal conversion efficiency under 808 nm irradiation. In addition, the nanoplatform achieves heat- and pH-sensitive drug release with precise control to specific-tumor sites, executing combined chemo-phototherapy functions. Besides, it functions as a multimodal bioimaging agent of photothermal, fluorescence, and magnetic resonance imaging for the accurate diagnosis and guidance of therapy. As validated by in vivo and in vitro assays, the TME-responsive nanoplatform is highly biocompatible and effectively obliterates 4T1 tumor xenografts on nude mice after triple-synergetic treatment. This work presents a rational design of versatile nanoplatforms, which modulate the TME to enable high therapeutic performance and multiplexed imaging, which provides an innovative paradigm for targeted tumor therapy.

The limited efficacy of “smart” nanotheranostic agents in eradicating tumors calls for the development of highly desirable nanoagents with diagnostics and therapeutics. Herein, to surmount these challenges, we constructed an intelligent nanoregulator by coating a mesoporous carbon nitride (C3N4) layer on a core–shell nitrogen-doped graphene quantum dot (N-GQD)@hollow mesoporous silica nanosphere (HMSN) and decorated it with a P-PEG-RGD polymer, to achieve active-targeting delivery (designated as R-NCNP). Upon irradiation, the resultant R-NCNP nanoregulators exhibit significant catalytic breakdown of water molecules, causing a sustainable elevation of oxygen level owing to the C3N4 shell, which facilitates tumor oxygenation and relieves tumor hypoxia. The generated oxygen bubbles serve as an echogenic source, triggering tissue impedance mismatch, thereby enhancing the generation of an echogenicity signal, making them laser-activatable ultrasound imaging agents. In addition, the encapsulated photosensitizers and C3N4-layered photosensitizer are simultaneously activated to maximize the yield of ROS, actualizing a triple-photosensitizer hybrid nanosystem exploited for enhanced PDT. Intriguingly, the N-GQDs endow the R-NCNP nanoregulator with a photothermal effect for hyperthemia, making it exhibit considerable photothermal outcomes and infrared thermal imaging (IRT). Importantly, further analysis reveals that the polymer-modified R-NCNPs actively target specific tumor tissues and display a triple-modal US/IRT/FL imaging-assisted cooperative PTT/PDT for real-time monitoring of tumor ablation and therapeutic evaluation. The rational synergy of triple-model PDT and efficient PTT in the designed nanoregulator confers excellent anticancer effects, as evidenced by in vitro and in vivo assays, which might explore more possibilities in personalized cancer treatment.

Nanomaterials based on hybrid scaffolds have shown a high potential to promote osteointegration and bone regeneration. In this study, a novel nanocomposite scaffold was synthesized via a cross-linking/hydrothermal/freeze-drying method, resulting in layer-by-layer structures with functional and structural properties mimicking the natural bone. The hierarchical structures of the scaffold were reinforced with nitrogen-doped multiwalled carbon nanotubes (N-MWCNTs), cellulose, and nanohydroxyapatite. The N-MWCNT/Cel/nHA scaffolds were characterized and evaluated in terms of structure, morphology, biocompatibility, cellular responses, and bone repair efficiency in vivo. The resulting scaffolds showed that incorporation of 1 wt % N-MWCNTs into the hybrid scaffold with micropores (∼5 μm) significantly improved its mechanical properties, although the surface morphology of the scaffold tended to be rough and porous. Importantly, the resulting scaffolds supported in vitro cellular attachment, proliferation, viability, and mineralization of bone mesenchymal stem cells (BMSCs). On the other hand, incorporation of N-MWCNTs into the scaffold induced preferential differentiation of BMSCs to osteogenic lineage accompanied by increased alkaline phosphatase activity and expression of key osteogenic genes. Furthermore, 12 weeks after implantation, the 1%N-MWCNT/Cel/nHA porous scaffolds successfully cicatrized a distal femoral condyle critical size defect in rabbit without obvious inflammatory responses, as indicated by the results of the Micro-CT and histological analyses. In vitro and in vivo experiments confirmed that the scaffolds not only improved the interface bonding with bone tissue but also accelerated the new bone formation and regeneration by up-regulating signaling molecules that are involved in cell proliferation and differentiation. These results indicated that the novel N-MWCNT/Cel/nHA scaffold is an efficient platform for osteogenesis research and bone regeneration medicine.

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Gold nanostars (AuNSs) are nanoparticles with intricate three-dimensional structures and shape-dependent optoelectronic properties. For example, AuNSs uniquely display three distinct surface curvatures, i.e. neutral, positive, and negative, which provide different environments to adsorbed ligands. Hence, these curvatures are used to introduce different surface chemistries in nanoparticles. This review summarizes and discusses the role of surface curvature in AuNS properties and its impact on biomedical and chemical applications, including surface-enhanced Raman spectroscopy, contrast agent performance, and catalysis. We examine the main synthetic approaches to generate AuNSs, control their morphology, and discuss their benefits and drawbacks. We also describe the optical characteristics of AuNSs and discuss how these depend on nanoparticle morphology. Finally, we analyze how AuNS surface curvature endows them with properties distinctly different from those of other nanoparticles, such as strong electromagnetic fields at the tips and increased hydrophilic environments at the indentations, together making AuNSs uniquely useful for biosensing, imaging, and local chemical manipulation.

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