The combination of chemotherapy with photodynamic therapy (PDT) has attracted broad attention as it can overcome limitations of conventional chemo-treatment by using different modes of action. However, the efficacy of PDT to treat solid tumors is severely affected by hypoxia in tumors.Methods: In this study, we developed oxygen-generating theranostic nanoparticles (CDM NPs) by hierarchically assembling doxorubicin (DOX), chlorin e6 (Ce6) and colloidal manganese dioxide (MnO2) with poly (ε-caprolactone-co-lactide)-b-poly (ethylene glycol)-b-poly (ε-caprolactone-co-lactide) for treating breast cancer. The in vitro and in vivo antitumor efficacy and imaging performance were investigated.Results: The theranostic nanoparticles showed high stability and biocompatibility both in vitro and in vivo. MnO2 within the nanoparticles could trigger decomposition of excessive endogenous H2O2 in the tumor microenvironment to generate oxygen in-situ to relieve tumor hypoxia. With enhanced oxygen generation, the PDT effect was significantly improved under laser-irradiation. More importantly, this effect together with that of DOX was able to dramatically promote the combined chemotherapy-PDT efficacy of CDM NPs in an MCF-7 tumor-bearing mouse model. Furthermore, the real-time tumor accumulation of the nanocomposites could be monitored by fluorescence imaging, photoacoustic (PA) imaging and magnetic resonance imaging (MRI).Conclusion: The designed CDM NPs are expected to provide an alternative way of improving antitumor efficacy by combined chemo-PDT further enhanced by oxygen generation, and would have broad applications in cancer theranostics.
The wide clinical application of photodynamic therapy (PDT) is hampered by poor water solubility, low tumor selectivity, and nonspecific activation of photosensitizers, as well as tumor hypoxia which is common for most solid tumors. To overcome these limitations, tumor-targeting, redox-activatable, and oxygen self-enriched theranostic nanoparticles are developed by synthesizing chlorin e6 (Ce6) conjugated hyaluronic acid (HA) with reducible disulfide bonds (HSC) and encapsulating perfluorohexane (PFH) within the nanoparticles (PFH@HSC). The fluorescence and phototoxicity of PFH@HSC nanoparticles are greatly inhibited by a self-quenching effect in an aqueous environment. However, after accumulating in tumors through passive and active tumor-targeting, PFH@HSC appear to be activated from "OFF" to "ON" in photoactivity by the redox-responsive destruction of the vehicle's structure. In addition, PFH@HSC can load oxygen within lungs during blood circulation, and the oxygen dissolved in PFH is slowly released and diffuses over the entire tumor, finally resulting in remarkable tumor hypoxia relief and enhancement of PDT efficacy by generating more singlet oxygen. Taking advantage of the excellent imaging performance of Ce6, the tumor accumulation of PFH@HSC can be monitored by fluorescent and photoacoustic imaging after intravenous administration into tumor-bearing mice. This PFH@HSC nanoparticle might have good potential for dual imaging-guided PDT in hypoxic solid tumor treatment.
It has been recognized that the cooperative activation by two or more catalytic centers with proper proximity could greatly increase the activity and enantioselectivity of homogeneous chiral catalysts through a specific control of the transition state, like in enzymatic catalysis.[1] If the cooperative activation could be realized in heterogeneous asymmetric catalysis, it may provide new possibilities for the development of highperformance heterogeneous catalysts, especially solid catalysts. This area is of ongoing academic and industrial interest for its potential advantages, such as in the separation and recycling of catalysts, continuous flow operations, and for the easy purification of products. [2] However, the generation of such a cooperative activation in a solid catalyst is difficult, because of the inability to elaborately control the proper proximity and the relative conformation of the active centers. If transition-metal complexes are confined but allowed to move freely in the isolated nanospace of a porous solid, the proper proximity and the relative conformation of the catalysts required for the cooperative activation could be realized through precisely adjusting the loadings and types of the transition-metal complexes in a confined space. Herein we demonstrate that the cooperative activation effect in the hydrolytic kinetic resolution (HKR) of epoxides could be greatly enhanced by confining [Co(salen)] (salen = (R,R)-N,N'-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediamine) complexes in the isolated nanocages of SBA-16 with a high local concentration and thus generated a more active solid catalyst compared with the homogeneous counterpart.The cagelike mesoporous silica SBA-16 with isolated cages connected by a small pore entrance was chosen as the solid host. In comparison with microporous zeolites, which have pore diameters of less than 2 nm and can also be used as host materials to confine metal complex catalysts, [3] the nanocages of SBA-16 is large enough (the cage size is tunable between 4-ca. 8 nm) to accommodate a desired number of transition-metal complexes in the confined space.[4] The transition-metal complex [Co(salen)] was chosen as the model catalyst because this catalyst has been demonstrated to have a cooperative activation effect in the HKR of terminal epoxides. [5] After introducing a given number of [Co(salen)] complexes in the nanocages of SBA-16, the pore entrance size was reduced through a silylation reaction. Propyltrimethoxysilane, which has a moderate hydrophobicity, was chosen as the silylating reagent not only to reduce the pore entrance size but also to modify the inner surface of SBA-16, thereby optimizing the diffusion rates of epoxides and 055, 0.087, 0.157, and 0.225 wt % corresponds to 1.2, 1.9, 3.4, and 4.9 [Co(salen)] complexes, respectively, accommodated in each nanocage of SBA-16.The catalytic performances of these solid catalysts with different Co contents were evaluated in the HKR of propylene epoxide under identical reaction conditions (Figure 1). The...
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