Chemodynamic therapy (CDT) utilizes iron-initiated Fenton chemistry to destroy tumor cells by converting endogenous H O into the highly toxic hydroxyl radical ( OH). There is a paucity of Fenton-like metal-based CDT agents. Intracellular glutathione (GSH) with OH scavenging ability greatly reduces CDT efficacy. A self-reinforcing CDT nanoagent based on MnO is reported that has both Fenton-like Mn delivery and GSH depletion properties. In the presence of HCO , which is abundant in the physiological medium, Mn exerts Fenton-like activity to generate OH from H O . Upon uptake of MnO -coated mesoporous silica nanoparticles (MS@MnO NPs) by cancer cells, the MnO shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn , resulting in GSH depletion-enhanced CDT. This, together with the GSH-activated MRI contrast effect and dissociation of MnO , allows MS@MnO NPs to achieve MRI-monitored chemo-chemodynamic combination therapy.
Multifunctional nanocomposites have the potential to integrate sensing, diagnostic, and therapeutic functions into a single nanostructure. Herein, we synthesize Fe 3 O 4 @polydopamine core-shell nanocomposites (Fe 3 O 4 @PDA NCs) through an in situ self-polymerization method. Dopamine, a melanin-like mimic of mussel adhesive proteins, can self-polymerize to form surface-adherent polydopamine (PDA) films onto a wide range of materials including Fe 3 O 4 nanoparticles used here. In such nanocomposites, PDA provides a number of advantages, such as near-infrared absorption, high fluorescence quenching efficiency, and a surface for further functionalization with biomolecules. We demonstrate the ability of the Fe 3 O 4 @PDA NCs to act as theranostic agents for intracellular mRNA detection and multimodal imaging-guided photothermal * Address correspondence to hhyang@fio.org.cn, gangliu.cmitm@xmu.edu.cn.. Conflict of Interest:The authors declare no competing financial interest. Supporting Information Available:Additional information as noted in the text. This material is available free of charge via the Internet at http://pubs.acs.org. Messenger RNA (mRNA), a single-stranded ribonucleic acid, is also the blueprint for the cellular production of proteins. Moreover, some mRNAs are disease-relevant and can be utilized as markers to determine the stage of the disease. 22 Recently, several methods such as microarray analysis 23 and real-time polymerase chain reaction (RT-PCR) 24 have been developed for mRNA detection. Although these methods are effective for detecting mRNA expression in bulk samples, they are incapable of identifying cell-to-cell mutations. Significantly, many important biological processes not only are related with bulk mRNA expression, but also rely highly on cell-to-cell variations in mRNA. 25 Thus, it is necessary to develop useful approaches for detecting mRNA in living cells. [26][27][28][29][30][31][32] In this work, we fabricated multifunctional Figure 1a). Furthermore, we demonstrated that PDA can adsorb dye-labeled singlestranded DNA (ssDNA) probe and effectively quench the fluorescence of the dye. In the presence of the target, the specific binding between the dye-labeled ssDNA probe and its Figure 1c). Our results suggest a high potential for the use of PDA in the construction of multifunctional nanocomposites for simultaneous diagnosis and therapy of cancer. HHS Public Access RESULTS AND DISCUSSIONFe 3 O 4 NPs were easily coated with a uniform PDA shell by dispersing them in an alkaline DA solution and mildly shaking at room temperature for 4 h. Transmission electron microscopy (TEM) revealed that approximately a 4 nm thick PDA shell was wrapped on the surface of the Fe 3 O 4 NPs after self-polymerization of the DA ( Figure 2a). The dynamic light scattering (DLS) data showed that the hydrodynamic diameter of the Fe 3 O 4 NPs was increased after the PDA coating (Supporting Information Figure S1), which is consistent with the TEM results. Moreover, the Fe 3 O 4 @PDA NCs exhibited excelle...
Chemodynamic therapy (CDT) utilizes iron‐initiated Fenton chemistry to destroy tumor cells by converting endogenous H2O2 into the highly toxic hydroxyl radical (.OH). There is a paucity of Fenton‐like metal‐based CDT agents. Intracellular glutathione (GSH) with .OH scavenging ability greatly reduces CDT efficacy. A self‐reinforcing CDT nanoagent based on MnO2 is reported that has both Fenton‐like Mn2+ delivery and GSH depletion properties. In the presence of HCO3−, which is abundant in the physiological medium, Mn2+ exerts Fenton‐like activity to generate .OH from H2O2. Upon uptake of MnO2‐coated mesoporous silica nanoparticles (MS@MnO2 NPs) by cancer cells, the MnO2 shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn2+, resulting in GSH depletion‐enhanced CDT. This, together with the GSH‐activated MRI contrast effect and dissociation of MnO2, allows MS@MnO2 NPs to achieve MRI‐monitored chemo–chemodynamic combination therapy.
Multifunctional nanoplatforms with integrated diagnostic and therapeutic functions have attracted tremendous attention. Especially, the second near-infrared (NIR-II) light response-based nanoplatforms hold great potential in cancer theranostic applications, which is because the NIR-II window provides larger tissue penetration depth and higher maximum permissible exposure (MPE) than that of the well-studied first near-infrared (NIR-I) window. Herein, we for the first time present a two-dimensional (2D)-nanoplatform based on Cu2MnS2 nanoplates (NPs) for magnetic resonance imaging (MRI)/multispectral optoacoustic tomography (MSOT) dual-modal imaging-guided photothermal therapy (PTT) of cancer in the NIR-II window. Methods: Cu2MnS2 NPs were synthesized through a facile and environmentally friendly process. A series of experiments, including the characterization of Cu2MnS2 NPs, the long-term toxicity of Cu2MnS2 NPs in BALB/c nude mice, the applications of Cu2MnS2 NPs for in vitro and in vivo MRI/MSOT dual-modal imaging and NIR-II PTT of cancer were carried out. Results: The as-synthesized Cu2MnS2 NPs exhibit low cytotoxicity, excellent biocompatibility as well as high photothermal conversion efficiency (~49.38%) and outstanding photostability. Together with their good T1-shortening effect and strong absorbance in the NIR-I and NIR-II region, the Cu2MnS2 NPs display high-contrast imaging performance both in MRI and MSOT (900 nm laser source). Moreover, the subsequent in vitro and in vivo results demonstrate that the Cu2MnS2 NPs possess excellent PTT efficacy under 1064 nm laser irradiation with a low power density (0.6 W cm-2). In addition, the detailed long-term toxicity studies further confirming the safety of Cu2MnS2 NPs in vivo. Conclusion: We have developed a new 2D Cu2MnS2 NPs as multifunctional theranostic agents for MRI/MSOT dual-modal imaging-guided PTT of cancer in the NIR-II window. Such biocompatible Cu2MnS2 NPs might provide a new perspective for exploring new 2D-based nanoplatforms with improved properties for clinical applications in the future.
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