Immunotherapy assays using immunoadjuvants and tumor antigens could greatly increase the survival rates of patients with malignant tumors. As effective carriers, metal-organic frameworks (MOFs) have been widely utilized in cancer therapy due to their remarkable histocompatibility and low toxicity. Herein, we constructed a multimodal imaging-guided synergistic cancer photoimmunotherapy by employing a specific MOF (MIL101-NH
2
) as the core carrier; the MOF was dual-dressed with photoacoustic and fluorescent signal donors (indocyanine green, ICG) and immune adjuvants (cytosine-phosphate-guanine sequence, CpG) and named ICG-CpG@MOF. This nanocarrier could passively target the tumor site through the EPR effect and achieve multimodal imaging (fluorescence, photoacoustic, photothermal and magnetic resonance imaging) of the tumor. Synergistic cancer photoimmunotherapy was achieved via simultaneous photodynamic and photothermal methods with 808 nm laser irradiation. ICG-CpG@MOF achieved the GSH-controlled release of immunoadjuvant into the tumor microenvironment. Furthermore, the released tumor-associated antigen along with CpG could induce the transformation of tumor cells from cold to hot by activating the immune system, which significantly enhanced tumor cytotoxicity and achieved high cure rates with minimal side-effects. This strategy utilizing multimodal imaging and synergistic cancer photoimmunotherapy provides a promising approach for the diagnosis and treatment of cancer.
Background
The design of stable and biocompatible black phosphorus-based theranostic agents with high photothermal conversion efficiency and clear mechanism to realize MRI-guided precision photothermal therapy (PTT) is imminent.
Results
Herein, black phosphorus nanosheets (BPs) covalently with mono-dispersed and superparamagnetic ferrous selenide (FeSe2) to construct heteronanostructure nanoparticles modified with methoxy poly (Ethylene Glycol) (mPEG-NH2) to obtain good water solubility for MRI-guided photothermal tumor therapy is successfully designed. The mechanism reveals that the enhanced photothermal conversion achieved by BPs-FeSe2-PEG heteronanostructure is attributed to the effective separation of photoinduced carriers. Besides, through the formation of the P-Se bond, the oxidation degree of FeSe2 is weakened. The lone pair electrons on the surface of BPs are occupied, which reduces the exposure of lone pair electrons in air, leading to excellent stability of BPs-FeSe2-PEG. Furthermore, the BPs-FeSe2-PEG heteronanostructure could realize enhanced T2-weighted imaging due to the aggregation of FeSe2 on BPs and the formation of hydrogen bonds, thus providing accurate PTT guidance and generating hyperthermia to inhabit tumor growth under NIR laser with negligible toxicity in vivo.
Conclusions
Collectively, this work offers an opportunity for fabricating BPs-based heteronanostructure nanomaterials that could simultaneously enhance photothermal conversion efficiency and photostability to realize MRI-guided cancer therapy.
Graphic abstract
Development of a rapid and sensitive method for Aβ(1-42) aggregation detection is of great importance to overcome the limitations of conventional techniques. In this study, we developed a label-free paper-based electrochemiluminescence sensor for amyloid-β aggregation detection toward potential diagnosis of Alzheimer's disease (AD). The paper-based chip used in the system serves as a low-cost and disposable detection method. In this detection platform, the bonding of [Ru(phen)2dppz]2+ to Aβ(1-42) aggregates results in enhanced electrochemiluminescence due to the change in the polarity of the microenvironment when [Ru(phen)2dppz]2+ intercalated into the β-sheets during oligomerization. The oligomerization process of Aβ(1-42) can be monitored in real time by the novel method, and as low as 100 pM equivalent monomer concentration of Aβ(1-42) could be detected simultaneously. In addition, the cerebrospinal fluid of transgenic AD model mice was tested by this method, which is highly consistent with genetic identification. In addition, we demonstrated that this detection platform could be a potential new method for the screening of Aβ(1-42) aggregation inhibitors, highlighting the practical application capacity of this platform. The platform is label free, low cost and sensitive. Therefore, the proposed platform holds great promise for the diagnosis of AD.
Acute myocardial infarction is a major global health problem, and the repair of damaged myocardium is still a major challenge. Myocardial injury triggers an inflammatory response: immune cells infiltrate into the myocardium while activating myofibroblasts and vascular endothelial cells, promoting tissue repair and scar formation. Fragments released by cardiomyocytes become endogenous “danger signals”, which are recognized by cardiac pattern recognition receptors, activate resident cardiac immune cells, release thrombin factors and inflammatory mediators, and trigger severe inflammatory responses. Inflammatory signaling plays an important role in the dilation and fibrosis remodeling of the infarcted heart, and is a key event driving the pathogenesis of post-infarct heart failure. At present, there is no effective way to reverse the inflammatory microenvironment in injured myocardium, so it is urgent to find new therapeutic and diagnostic strategies. Nanomedicine, the application of nanoparticles for the prevention, treatment, and imaging of disease, has produced a number of promising applications. This review discusses the treatment and challenges of myocardial injury and describes the advantages of functional nanoparticles in regulating the myocardial inflammatory microenvironment and overcoming side effects. In addition, the role of inflammatory signals in regulating the repair and remodeling of infarcted hearts is discussed, and specific therapeutic targets are identified to provide new therapeutic ideas for the treatment of myocardial injury.
A novel paper-based bipolar electrode-electrochemiluminescence (pBPE-ECL) switch system was used for the rapid, labelfree, and sensitive detection of Hg 2 + . In the proposed approach, Hg 2 + selectively mediates two thymine-enriched singlestranded DNA probes to form double-stranded DNA (dsDNA). In the presence of Hg 2 + , the "light-switch" molecule [Ru(phen) 2 dppz] 2 + can freely intercalate into the base pairs of the dsDNA, resulting in intense ECL emission. The assay takes advantage of the wireless pBPE-ECL platform to yield a low-cost, disposable, and sensitive analysis. The system has a limit of 0.1 nM for Hg 2 + detection. We also showed that the system can be used to distinguish Hg 2 + over other metal ions, including Pb
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