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Triple-negative breast cancer (TNBC) has been a clinical challenge due to its high recurrence and metastasis rates. Chemotherapy remains the primary treatment for TNBC after surgery ablation, but it lacks targeted specificity and causes side effects in normal tissues. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is significantly expressed in TNBC cells, and small interference RNA (siRNA) targeting ROR1 can effectively suppress ROR1 gene expression, thereby inhibiting proliferation and metastasis. However, clinical application of ROR1 siRNA is limited by susceptibility to clearance and difficulty in endosomal escape. In this study, the docetaxel (DTX) prodrug nanoparticle BBRM delivering ROR1 siRNA was constructed. The BBRM could be effectively internalized by tumor cells and endosomal escape to release DTX and ROR1 siRNA. In 4T1 tumor-bearing mice, BBRM could be targeting delivered to tumor and lung tissues, with good biosafety, achieving a tumor inhibition rate of 74.1 % and inhibiting lung metastasis. By integrating chemotherapy and RNA interference therapy, BBRM successfully co-delivered chemotherapeutic agents and siRNA to improve the therapeutic efficacy of triple-negative breast cancer and provided a promising strategy for clinical transformation. Chemotherapy is still the primary treatment for triple-negative breast cancer (TNBC) after surgery ablation, but it causes side effects without targeting capacity. ROR1 is significantly expressed in TNBC cells, and RNA interference for ROR1 can suppress ROR1 gene expression to inhibit tumor proliferation. However, as oligonucleotides, effect of ROR1 siRNA is limited by susceptibility to clearance and difficulty in endosomal escape. In this work, we designed a nanodevice based on a docetaxel (DTX) prodrug that targets ROR1 for the synergistic therapy of TNBC. We constructed a nanoparticle (BBRM) for co-delivery of the DTX and ROR1 siRNA. The BBRM could be effectively internalized by tumor cells and endosomal escape. The ROR1 siRNA downregulated ROR1 protein expression and improved the anti-proliferative and anti-metastatic effects. In addition, BBRM reversed the immunosuppressive tumor microenvironment, thus improving breast cancer therapeutic efficacy. It was a pioneering investigation in synergistic chemo-gene therapy by co-delivering DTX and ROR1 siRNA for TNBC treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

• The immunogenic cell death (ICD) of cancer cells promotes immune response. • Nanosized drug delivery systems can induce ICD. • Anti-cancer nanomedicines reduce systemic side effects and enhance tumor targeting capacity. • Different strategies for inducing ICD improve the efficacy of cancer immunotherapy. Many anti-cancer therapies can induce or enhance the immunogenic cell death (ICD), a process that releases damage-associated molecular patterns (DAMPs) to prime antigen processing and presentation necessary for successful cancer immunotherapy. However, the clinical potential of these therapies, especially the chemotherapy, is limited by serious systemic side effects, because of their non-specific accumulation out of the tumors. Nanosized drug delivery systems (NDDSs) can improve the specificity of anti-cancer therapies, which enhance ICD in the tumor while alleviating toxicities. In this review, we summarize recent progress of ICD-inducing NDDSs with a focus on their enhanced safety and efficacy for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

The abnormal tumor vascular system and long distances among cells inside tumors and blood vessels lead to restricted oxygen content and diffusion impairment in the tumor tissues, which are two essential factors contributing to hypoxia. Since hypoxia is an important feature of malignant solid tumors, it is closely related to the development of tumors and resistance to therapies. Recently, various anti-hypoxia treatments based on nanosized drug delivery systems (NDDSs) have been developed to enhance the efficacy of cancer therapy, providing a feasible solution for overcoming the obstacles to cancer treatments caused by hypoxia. In this review, the latest research progress on improving cancer therapy by anti-hypoxia NDDSs based on various mechanisms, including increasing oxygen supply, reducing oxygen consumption, and inhibiting hypoxia-related signaling pathways, is summarized. On the basis of discussing the advantages and shortcomings of these strategies, we propose possible directions and perspectives on further studies and clinical translation. [Display omitted] • The abnormal blood vessels and aberrant extracellular matrix in tumors cause hypoxia. • Hypoxia promotes tumor progression and resistance to cancer therapy. • Nanosized drug delivery systems can relieve hypoxia via different mechanisms. • Anti-hypoxia nanosized drug delivery systems enhance cancer therapy efficiency. [ABSTRACT FROM AUTHOR]

The purpose of this work was to explore in - situ synchrotron wide-angle X-ray diffraction (WAXD) as a rapid and accurate tool to screen and monitor the formation of cocrystal/salts during heating. The active pharmaceutical ingredients (caffeine, carbamazepine and lamotrigine) were respectively mixed with the coformer (saccharin), and then heated by the hot stage. Real-time process monitoring was performed using synchrotron WAXD to assess cocrystal formation and subsequently compared to differential scanning calorimetry (DSC) measurements. The effect of heating rates and cocrystal growth behavior were investigated. Synchrotron WAXD was fast and sensitive to detect cocrystal formation with the appearance of characteristic diffraction rings, even at the heating rate of 30 °C/min, while DSC curves showed overlapped peaks. Unlike the indirect characterization of DSC on endo/exothermic peaks, synchrotron WAXD can directly and qualitatively determine cocrystal by diffraction peaks. The diffraction intensity–temperature curves and the corresponding first-derivative curves clearly exhibited the growth behavior of cocrystal upon heating, providing useful information to optimize the process temperature of hot melt extrusion to continuously manufacture cocrystal. The study suggests that in - situ synchrotron WAXD could provide a one-step process to screen cocrystal at high efficiency and reveal the details of cocrystal/salts growth behavior. [ABSTRACT FROM AUTHOR]