3D Printed Conductive Hydrogel Patch Incorporated with MSC@GO for Efficient Myocardial Infarction Repair.

Myocardial infarction (MI) results in an impaired heart function. Conductive hydrogel patch-based therapy has been considered as a promising strategy for cardiac repair after MI. In our study, we fabricated a three-dimensional (3D) printed conductive hydrogel patch made of fibrinogen scaffolds and mesenchymal stem cells (MSCs) combined with graphene oxide (GO) flakes (MSC@GO), capitalizing on GO's excellent mechanical property and electrical conductivity. The MSC@GO hydrogel patch can be attached to the epicardium via adhesion to provide strong electrical integration with infarcted hearts, as well as mechanical and regeneration support for the infarcted area, thereby up-regulating the expression of connexin 43 (Cx43) and resulting in effective MI repair in vivo. In addition, MI also triggers apoptosis and damage of cardiomyocytes (CMs), hindering the normal repair of the infarcted heart. GO flakes exhibit a protective effect against the apoptosis of implanted MSCs. In the mouse model of MI, MSC@GO hydrogel patch implantation supported cardiac repair by reducing cell apoptosis, promoting gap connexin protein Cx43 expression, and then boosting cardiac function. Together, this study demonstrated that the conductive hydrogel patch has versatile conductivity and mechanical support function and could therefore be a promising candidate for heart repair.

Nanoscale MOFs in nanomedicine applications: from drug delivery to therapeutic agents.

Metal-organic frameworks (MOFs) hold great promise for widespread applications in biomedicine and nanomedicine. MOFs are one of the most fascinating nanocarriers for drug delivery, benefiting from their high porosity and facile modification. Furthermore, the tailored components of MOFs can be therapeutic agents for various treatments, including drugs as organic ligands of MOFs, active metal as central metal ions of MOFs, and their combinations as carrier-free MOF-based nanodrug. In this review, the advances in delivery systems and applications as therapeutic agents for nanoscale MOF-based materials are summarized. The challenges of MOFs in clinical translation and the future directions in the field of MOFs therapy are also discussed. We hope that more researchers will focus their attention on advancing and translating MOF-based nanodrugs into pre-clinical and clinical applications.

Silk Fibroin-Induced Gadolinium-Functionalized Gold Nanoparticles for MR/CT Dual-Modal Imaging-Guided Photothermal Therapy.

The development of multifunction nanoplatforms integrating accurate diagnosis and efficient therapy is of great significance for the precise treatment of tumors. Gold nanoparticles (AuNPs) possessing hallmark features of computed tomography (CT) imaging and photothermal conversion capability hold great potential in tumor theranostics. In this study, taking the advantages of outstanding biocompatibility, interesting anti-inflammatory and immunomodulatory properties, and abundant amino acid residues of silk fibroin (SF), a multifunctional Gd-hybridized AuNP nanoplatform was constructed using SF as a stabilizer and reductant via a facile one-pot biomimetic method, denoted as Gd:AuNPs@SF. The obtained Gd:AuNPs@SF possessed fascinating biocompatibility and excellent photothermal conversion efficiency. Functionalized with Gd, Gd:AuNPs@SF exhibited super tumor-contrasted imaging performance in magnetic resonance (MR) and CT imaging modalities. Moreover, Gd:AuNPs@SF, with strong NIR absorbance, demonstrated that it could effectively kill tumor cells in vitro, and was also proved to successfully ablate tumor tissues through MR/CT imaging-guided photothermal therapy (PTT) without systemic toxicity in Pan02 xenograft C57BL/6 mouse models. We successfully synthesized Gd:AuNPs@SF for MR/CT dual-mode imaging-guided PTT via a facile one-pot biomimetic method, and this biomimetic strategy can also be used for the construction of other multifunction nanoplatforms, which is promising for precise tumor theranostics.

hESCs-Derived Early Vascular Cell Spheroids for Cardiac Tissue Vascular Engineering and Myocardial Infarction Treatment.

Transplanting functional cells to treat myocardial infarction (MI), a major disease threatening human health, has become the focus of global therapy. However, the efficacy has not been well anticipated, partly due to the lack of microvascular system that supplies nutrients and oxygen. Here, spheroids of early vascular cells (EVCs) derived from human embryonic stem cells (hESCs), rather than single-cell forms, as transplant "seeds" for reconstructing microvascular networks, are proposed. Firstly, EVCs containing CD34+ vascular progenitor cells are identified, which effectively differentiate into endothelial cells in situ and form vascular networks in extracellular matrix (ECM) hydrogel. Secondly, cardiac microtissues and cardiac patches with well-organized microvasculature are fabricated by three-dimensional (3D) co-culture or bioprinting with EVCs and cardiomyocytes in hydrogel. Notably, in 3D-bioprinted myocardial models, self-assembly vascularization of EVC spheroids is found to be significantly superior to EVC single cells. EVC spheroids are also injected into ischemic region of MI mouse models to explore its therapeutic potential. These findings uncover hESCs-derived EVC spheroids rather than single cells are more accessible for complex vasculature engineering, which is of great potential for cardiac tissue vascular engineering and MI treatment by cell therapy.

Dual-targeted and MRI-guided photothermal therapy via iron-based nanoparticles-incorporated neutrophils.

Nanoparticle-mediated photothermal therapy (PTT) has shown promising capability for tumor therapy through the high local temperature at the tumor site generated by a photothermal agent (PTA) under visible or near-infrared (NIR) irradiation. Improving the accumulation of PTA at the tumor site is crucial to achieving effective photothermal treatment. Here, we developed temperature-activatable engineered neutrophils (Ne) by combining indocyanine green (ICG)-loaded magnetic silica NIR-sensitive nanoparticles (NSNP), which provide the potential for dual-targeted photothermal therapy. The combined effect of neutrophil targeting and magnetic targeting increased the accumulation of PTA at the tumor site. According to magnetic resonance imaging (MRI), the retention of intravenous injected NSNP-incorporated neutrophils within the tumor site was markedly augmented as compared to free NSNP. Furthermore, when irradiated by NIR, NSNP could cause a high local temperature at the tumor site and the thermal stimulation of neutrophils. The heat can kill tumor cells directly, and also lead to the death of neutrophils, upon which active substances with tumor-killing efficacy will be released to kill residual tumor cells and thus reduce tumor recurrence. Thereby, our therapy achieved the elimination of malignancy in the mouse model of the pancreatic tumor without recurrence. Given that all materials used in this system have been approved for use in humans, the transition of this treatment method to clinical application is plausible.

2D CoOOH nanosheets as oxidase mimic for the colorimetric assay of sulfite in food.

Here, we report a rapid, sensitive and selective colorimetric assay for sulfite (SO32-) based on the intrinsic oxidase-like activity of 2D cobalt oxyhydroxide nanosheets (CoOOH NSs). The 2D CoOOH nanozyme could directly oxidize 3,3',5,5'-tetramethylbenzidine (TMB) into blue products (TMBox) in an aerobic solution without H2O2. Interestingly, the presence of SO32- could effectively inhibit the CoOOH NS-O2-TMB reaction system and thus caused changes in color and absorbance, which facilitated a colorimetric sensor for sulfite. After optimizing detection conditions, a facile and robust approach was developed for SO32- detection in food.

Melanoma Cell Membrane Biomimetic Versatile CuS Nanoprobes for Homologous Targeting Photoacoustic Imaging and Photothermal Chemotherapy.

Modulating the surface properties of nanoparticles (NPs) is an important approach to accomplish immune escape, prolonged the blood retention time, and enhance the ability of targeted drug delivery. The camouflage of cancer cell membrane onto nanoparticles has been proved to be an ideal approach to enhance active targeting ability of NPs. Herein, we isolated the membrane of melanoma cells to coat doxorubicin (DOX) and indocyanine green (ICG)-loaded hollow copper sulfide NPs (ID-HCuSNP@B16F10) for targeted photothermal therapy, photoacoustic imaging, and chemotherapy. A remarkable in vitro anticancer effect after irradiation and homologous targeting can be observed in B16F10 cells after the treatment of ID-HCuSNP@B16F10. Moreover, ID-HCuSNP@B16F10 exhibits excellent photothermal effect in melanoma animal models and achieves a high tumor ablation rate. This biomimetic system can realize high drug loading efficiency, enhanced targeting ability, and ideal antitumor efficiency.

Cell membrane camouflaged nanoparticles: a new biomimetic platform for cancer photothermal therapy.

Targeted drug delivery by nanoparticles (NPs) is an essential technique to achieve the ideal therapeutic effect for cancer. However, it requires large amounts of work to imitate the biomarkers on the surface of the cell membrane and cannot fully retain the bio-function and interactions among cells. Cell membranes have been studied to form biomimetic NPs to achieve functions like immune escape, targeted drug delivery, and immune modulation, which inherit the ability to interact with the in vivo environments. Currently, erythrocyte, leukocyte, mesenchymal stem cell, cancer cell and platelet have been applied in coating photothermal agents and anti-cancer drugs to achieve increased photothermal conversion efficiency and decreased side effects in cancer ablation. In this review, we discuss the recent development of cell membrane-coated NPs in the application of photothermal therapy and cancer targeting. The underlying biomarkers of cell membrane-coated nanoparticles (CMNPs) are discussed, and future research directions are suggested.

In vitro and in vivo targeting imaging of pancreatic cancer using a Fe3O4@SiO2 nanoprobe modified with anti-mesothelin antibody.

Pancreatic cancer is a highly malignant disease with a 5-year survival rate <5% mainly due to lack of early diagnosis and effective therapy. In an effort to improve the early diagnostic rate of pancreatic cancer, a nanoprobe Fe3O4@SiO2 modified with anti-mesothelin antibody (A-MFS) was prepared to target cells and tumor tissues highly expressing mesothelin in vitro (human pancreatic cancer cell line SW1990) and in vivo (subcutaneously transplanted tumors) studies. The A-MFS probe was successfully prepared and was spherical and uniform with a hydrodynamic diameter between 110 and 130 nm. Cell Counting Kit-8 testing indicated that A-MFS was nontoxic in vitro and in vivo studies. The in vitro study showed that the A-MFS probe specifically targeted SW1990 cells with high mesothelin expression. The in vivo study was conducted in Siemens 3.0 T magnetic resonance imaging. The average T2-weighted signal values of the xenografts were 966.533±31.56 before injecting A-MFS and 691.133±56.84 before injecting saline solution. After injection of 0.1 mL A-MFS via nude mouse caudal vein for 2.5 hours, the average T2-weighted signal of the xenograft decreased by 342.533±42.6. The signal value decreased by -61.233±33.9 and -58.7±19.4 after injection of the saline and Fe3O4@SiO2. The decrease of tumor signal by A-MFS was much more significant than that by saline and Fe3O4@SiO2 (P<0.05). The results demonstrated the high stability and nontoxicity of A-MFS, which effectively targeted pancreatic cancer in vitro and in vivo. A-MFS is a promising agent for diagnosis of pancreatic cancer.