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The heterogeneity of triple‐negative breast cancers (TNBC) remains challenging for various treatments. Ferroptosis, a recently identified form of cell death resulting from the unrestrained peroxidation of phospholipids, represents a potential vulnerability in TNBC. In this study, a high intensity focused ultrasound (HIFU)‐driven nanomotor is developed for effective therapy of TNBC through induction of ferroptosis. Through bioinformatics analysis of typical ferroptosis‐associated genes in the FUSCCTNBC dataset, gambogic acid is identified as a promising ferroptosis drug and loaded it into the nanomotor. It is found that the rapid motion of nanomotors propelled by HIFU significantly enhanced tumor accumulation and penetration. More importantly, HIFU not only actuated nanomotors to trigger effective ferroptosis of TNBC cells, but also drove nanomotors to activate ferroptosis‐mediated antitumor immunity in primary and metastatic TNBC models, resulting in effective tumor regression and prevention of metastases. Overall, HIFU‐driven nanomotors show great potential for ferroptosis‐immunotherapy of TNBC. [ABSTRACT FROM AUTHOR]

The potential of microRNA regulation in oncotherapy is limited by the lack of delivery vehicles. Herein, it is shown that fluoropolymer coated DNA nanoclews (FNCs) provide outstanding ability to deliver oligonucleotide through circulation and realize near infrared (NIR) light activated angiogenesis suppression to abrogate tumors. Oligonucleotides are loaded in DNA nanoclews through sequence specific bindings and then a fluorinated zwitterionic polymer is coated onto the surface of nanoclews. Further incorporating quantum dots in the polymer coating endows the vectors with NIR‐IIb (1500–1700 nm) fluorescence and NIR light triggered release ability. The FNC vector can deliver oligonucleotides to cancer cells systemically and realize on‐demand cytosolic release of the cargo with high transfection efficiency. Taking advantage of the NIR‐IIb emission, the whole delivery process of FNCs is visualized volumetrically in vivo with a NIR light sheet microscope. Loaded by FNCs, an oligonucleotide can effectively silence the target miRNA when activated with NIR light, and inhibit angiogenesis inside tumor, leading to complete ablation of cancer. These findings suggest FNCs can be used as an efficient oligonucleotide delivery platform to modulate the expression of endogenous microRNA in gene therapy of cancer. [ABSTRACT FROM AUTHOR]

Conventional chemotherapy is bothered by systematic toxicity and confined therapeutic effects. Gas therapy has emerged as a potent tumor treatment, and hydrogen sulfide (H2S), a traditional gasotransmitter, has been found to show a tumor inhibition effect. Therefore, we established a mesoporous organosilica-based H2S nanogenerator (MON-TPGS-DOX). Tetrasulfide bond-incorporated mesoporous organosilica nanoparticles were modified with d-α-tocopheryl polyethylene glycol succinate (TPGS), namely, MON-TPGS, and then loaded with doxorubicin (DOX) to obtain the nanogenerator. Tetrasulfide bonds in the nanogenerator could be triggered by glutathione (GSH) to release H2S, further resulting in the degradation of nanogenerator and DOX release. GSH consumption and H2S release led to oxidative stress in 4T1 cells, activation of apoptotic signaling cascades, and enhanced cell-killing effect. Furthermore, the nanogenerator effectively suppressed tumor growth in a tumor-bearing mice model with good biosafety, providing a promising approach for H2S-enhanced tumor chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract Internalization and dynamic subcellular distribution of thiol-capped CdTe quantum dots (QDs) in living cells were studied by means of laser scanning confocal microscopy. These unfunctionalized QDs were well internalized into human hepatocellular carcinoma and rat basophilic leukemia cells in vitro. Co-localizations of QDs with lysosomes and Golgi complexes were observed, indicating that in addition to the well-known endosome-lysosome endocytosis pathway, the Golgi complex is also a main destination of the endocytosed QDs. The movement of the endocytosed QDs toward the Golgi complex in the perinuclear region of the cell was demonstrated.

Ferroptosis, as a form of cell death different from apoptosis, is very promising for the treatment of cancer in nonapoptotic systems. Since iron is a key component in the induction of ferroptosis in cells, the use of iron-based nanomaterials in treating cancer through ferroptosis is of great significance. Therefore, in this study, magnetic nanoparticles (MNP) were coated with the zwitterionic polymer poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), and then loaded with sorafenib (SRF) to obtain drug-loaded composite nanoparticles MNP@PMPC-SRF. Fe3O4 provided a large number of ferric/ferrous ions as an iron source, releasing Fe2+ for the regulation of the ferroptosis process and enhancing the effect of the induced cellular ferroptosis on the treatment of colon cancer with SRF. The zwitterionic polymer PMPC effectively extended the blood circulation time, resulting in an enhanced tumor accumulation of the nanodrug. MNP@PMPC-SRF exhibited good biocompatibility for in vivo application and showed an excellent tumor inhibitory effect on HCT116 tumor-bearing nude mice. [ABSTRACT FROM AUTHOR]

The development of stimuli‐responsively degradable porous carriers for both controlled drug release and high biosafety is vitally important to their clinical translation, but still challenging at present. A new type of porphyrin–iron metal organic framework (Fe‐MOF) nanocrystals is engineered here as acid‐degradable drug carrier and hydrogen donor by the coordination between porphyrin and zero‐valence Fe atom. Fe‐MOF nanocrystals exhibit excellent acid‐responsive degradation for H2 generation and simultaneous release of the loaded drug for combined hydrogen‐chemotherapy of cancer multidrug resistance (MDR) and metastasis and for local hydrogen eradication of the off‐target induced toxic side effects of the drug to normal cells/tissues. Mechanistically, released H2 assists chemotherapeutic drug to efficiently inhibit cancer metastasis by immunoactivating intratumoral M1‐phenotype macrophages and consequently downregulating the expression of metastasis‐related matrix metalloproteinase‐2 (MMP‐2) and can also downregulate the expressions of both P‐glycoprotein (P‐gp) protein and adenosine triphosphate (ATP) in MDR cancer cells to sensitize chemotherapeutic drug for enhanced damage to mitochondria and DNA. High anti‐MDR/antimetastasis efficacies and high biocompatibility endow Fe‐MOF nanocrystals and the Fe‐MOF‐based nanomedicine with high potential for clinical translation. [ABSTRACT FROM AUTHOR]