Photodynamic therapy (PDT) is a promising antitumor treatment that is based on the photosensitizers that inhibit cancer cells by yielding reactive oxygen species (ROS) after irradiation of light with specific wavelengths. As a potential photosensitizer, titanium dioxide (TiO2) exhibits minimal dark cytotoxicity and excellent ultraviolet (UV) light triggered cytotoxicity, but is challenged by the limited tissue penetration of UV light. Herein, a novel near-infrared (NIR) light activated photosensitizer for PDT based on TiO2-coated upconversion nanoparticle (UCNP) core/shell nanocomposites (UCNPs@TiO2 NCs) is designed. NaYF4:Yb(3+),Tm(3+)@NaGdF4:Yb(3+) core/shell UCNPs can efficiently convert NIR light to UV emission that matches well with the absorption of TiO2 shells. The UCNPs@TiO2 NCs endocytosed by cancer cells are able to generate intracellular ROS under NIR irradiation, decreasing the mitochondrial membrane potential to release cytochrome c into the cytosol and then activating caspase 3 to induce cancer cell apoptosis. NIR light triggered PDT of tumor-bearing mice with UCNPs@TiO2 as photosensitizers can suppress tumor growth efficiently due to the better tissue penetration than UV irradiation. On the basis of the evidence of in vitro and in vivo results, UCNPs@TiO2 NCs could serve as an effective photosensitizer for NIR light mediated PDT in antitumor therapy.
As a noninvasive treatment modality, ultrasound (US)triggered sonodynamic therapy (SDT) shows broad and promising applications to overcome the drawbacks of traditional photodynamic therapy (PDT) in combating cancer. However, the SDT efficacy is still not satisfactory without oxygen (O 2 ) assistance. In addition, there is also much space to explore the SDT-based synergistic therapeutic modalities. Herein, a novel Pt-CuS Janus composed of hollow semiconductor CuS and noble metallic Pt was rationally designed and successfully synthesized. The hollow CuS shows a large inner cavity for loading sonosensitizer molecules (tetra-(4-aminophenyl) porphyrin, TAPP) to implement SDT. Moreover, the deposition of Pt not only enhances photothermal performance compared with those of CuS nanoparticles (NPs) due to the effect of the local electric field enhancement but also possesses nanozyme activity for catalyzing decomposition of endogenous overexpressed hydrogen peroxide (H 2 O 2 ) to produce O 2 that can overcome tumor hypoxia and augment the SDT-induced highly toxic reactive oxygen species (ROS) production for efficient cancer cell apoptosis. Importantly, the generated heat of Pt-CuS by 808 nm laser irradiation can accelerate the catalytic activity of Pt and elevate the O 2 level that further facilitates SDT efficacy. Interestingly, the thermally sensitive copolymer coated around the Janus can act as a smart switch to regulate the catalytic ability of Pt and control TAPP release that has a significant effect on modulating the therapeutic effect. The synergistic catalysis-enhanced SDT efficiency and highly photothermal effect almost realized complete tumor resection without obvious reoccurrence and simultaneously displayed a highly therapeutic biosafety. Furthermore, the high optical absorbance allows the as-synthesized Pt-CuS Janus for photoacoustic (PA) imaging and NIR thermal imaging. This work develops a versatile nanoplatform for a multifunctional theranostic strategy and broadens the biological applications by rationally designing their structure.
Ultrasound (US)-triggered sonodynamic therapy (SDT), as a promising noninvasive therapeutic modality, has received ever-increasing attention in recent years. Its specialized chemical agents, named sonosensitizers, are activated by low-intensity US to produce lethal reactive oxygen species (ROS) for oncotherapy. Compared with phototherapeutic strategies, SDT provides many noteworthy opportunities and benefits, such as deeper penetration depth, absence of phototoxicity, and fewer side effects. Nevertheless, previous studies have also demonstrated its intrinsic limitations. Thanks to the facile engineering nature of nanotechnology, numerous novel nanoplatforms are being applied in this emerging field to tackle these intrinsic barriers and achieve continuous innovations. In particular, the combination of SDT with other treatment strategies has demonstrated a superior efficacy in improving anticancer activity relative to that of monotherapies alone. Therefore, it is necessary to summarize the nanomaterial-assisted combinational sonodynamic cancer therapy applications. Herein, the design principles in achieving synergistic therapeutic effects based on nanomaterial engineering methods are highlighted. The ultimate goals are to stimulate the design of better-quality combined sonodynamic treatment schemes and provide innovative ideas for the perspectives of SDT in promoting its future transformation to clinical application.
Organic/inorganic hybrid lead halide perovskites are promising optoelectronic materials due to their unique structure, excellent properties, and fascinating potential applications in lighting, photovoltaic, etc. However, perovskite materials are very sensitive to moisture and polar solvent, which greatly hinders their practical applications. Here, highly luminescent perovskite-polystyrene composite beads with uniform morphology are prepared via a simple swelling-shrinking strategy. This process is carried out only in nonpolar toluene and hexane without the addition of any polar reagents. As a result, the as-prepared composite beads not only retain high luminescence but also exhibit superior water-resistant property. The composites emit strong luminescence after being immersed into water over nine months. Moreover, even in some harsh environments such as acid/alkali aqueous solution, phosphate buffer solution, and Dulbecco's modified eagle medium biological buffers, they still preserve high luminescence. The applications in light-emitting diodes and cellular labeling agents are also carried out to demonstrate their ultrastability.
It is of great importance in drug delivery to fabricate multifunctional nanocarriers with intelligent targeting properties, for cancer diagnosis and therapy. Herein, hollow-structured CuS@Cu S@Au nanoshell/satellite nanoparticles are designed and synthesized for enhanced photothermal therapy and photoswitchable targeting theranostics. The remarkably improved photothermal conversion efficiency of CuS@Cu S@Au under 808 nm near-infrared (NIR) laser irradiation can be explained by the reduced bandgap and more circuit paths for electron transitions for CuS and Cu S modified with Au nanoparticles, as calculated by the Vienna ab initio simulation package, based on density functional theory. By modification of thermal-isomerization RGD targeting molecules and thermally sensitive copolymer on the surface of nanoparticles, the transition of the shielded/unshielded mode of RGD (Arg-Gly-Asp) targeting molecules and shrinking of the thermally sensitive polymer by NIR photoactivation can realize a photoswitchable targeting effect. After loading an anticancer drug doxorubicin in the cavity of CuS@Cu S@Au, the antitumor therapy efficacy is greatly enhanced by combining chemo- and photothermal therapy. The reported nanohybrid can also act as a photoacoustic imaging agent and an NIR thermal imaging agent for real-time imaging, which provides a versatile platform for multifunctional theranostics and stimuli-responsive targeted cancer therapy.
Sonodynamic therapy (SDT) activated by ultrasound is attractive as a potential alternative to conventional phototriggered therapies owing to the deeper penetration depth and the absence of phototoxicity. Nevertheless, the low quantum yield of nano‐sonosensitizer and the tumor hypoxia remain significant challenges for SDT. Herein, a novel TiO2‐based nano‐sonosensitizer is reported to bilaterally enhance the quantum yield by simultaneous integration of precious metal Pt nanoparticles (NPs) and an oxygen‐deficient layer. Furthermore, the hollow cavity of TiO2 serves as a reservoir to load doxorubicin, an anticancer drug for chemotherapy as well as a molecular sonosensitizer for SDT. The decorated Pt NPs act as nanozymes to catalyze the decomposition of endogenous hydrogen peroxide for the generation of oxygen to alleviate tumor hypoxia, reduce resistance to chemotherapy, and provide sufficient oxygen source for subsequently facilitating SDT‐induced reactive oxygen species production. The high chemo‐sonodynamic synergistic efficacy is systematically demonstrated both in vitro and in vivo. More importantly, it is believed that the novel design and the new finding in the synthesis of Pt–TiO2 heterostructures can be popularized for the preparation and application of the semiconductor‐based nanoplatforms in many fields.
Light-sensitive yolk−shell nanoparticles (YSNs) as remote-controlled and stimuli-responsive theranostic platforms provide an attractive method for synergistic cancer therapy. Herein, a kind of novel stimuli-responsive multifunctional YSNs has been successfully constructed by integrating star-shaped gold (Au star) nanoparticles as the second near-infrared (NIR-II) photothermal yolks and biodegradable crystalline zeolitic imidazolate framework-8 (ZIF-8) as the shells. In this platform, a chemotherapeutic drug (doxorubicin hydrochloride, DOX) was encapsulated into the cavity, which can show the behavior of controlled release due to the degradation process of ZIF-8 in the mildly acidic tumor microenvironment. Upon the 1064 nm (NIR-II biowindow) laser irradiation, gold nanostar@ZIF-8 (Au@MOF) nanoparticles exhibited outstanding synergistic anticancer effect based on their photothermal and promoted cargo release properties. Moreover, the strong NIR region absorbance endows the Au@MOF of NIR thermal imaging and photoacoustic (PA) imaging properties. This work contributes to design a stimuliresponsive "all-in-one" nanocarrier that realizes bimodal imaging diagnosis and chemo-photothermal synergistic therapy.
Elaborately designed biocompatible nanoplatforms simultaneously achieving multimodal bioimaging and therapeutic functions are highly desirable for modern biomedical applications. Herein, uniform MoS2 nanoflowers with a broad size range of 80–180 nm have been synthesized through a facile, controllable, and scalable hydrothermal method. The strong absorbance of MoS2 nanoflowers at 808 nm imparts them with high efficiency and stability of photothermal conversion. Then a novel multifunctional composite of MoS2@Fe3O4‐ICG/Pt(IV) (labeled as Mo@Fe‐ICG/Pt) is designed by covalently grafting Fe3O4 nanoparticles with polyethylenimine (PEI) functionalized MoS2, and then loading indocyanine green molecules (ICG, photosensitizers) and platinum (IV) prodrugs (labeled as Pt(IV) prodrugs) on the surface of MoS2@Fe3O4. The resulting Mo@Fe‐ICG/Pt nanocomposites can achieve excellent magnetic resonance/infrared thermal/photoacoustic trimodal biomaging as well as remarkably enhanced antitumor efficacy of combined photothermal therapy, photodynamic therapy, and chemotherapy triggered by a single 808 nm NIR laser, thus leading to an ideal nanoplatform for cancer diagnosis and treatment in future.
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