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Abstract The development of nanotechnology has provided numerous possibilities for the diagnosis and treatment of cancer. Paradoxically, some in vivo experimental studies have also shown that nanoparticles (NPs) could promote tumor progression, but the specific mechanism is not yet clear. Primary tumors can release extracellular vesicles (EVs) which can promote the inoculation and growth of tumor cells that have metastasized to distant organs. So, whether nanomaterials can promote tumor progression through tumor-derived EVs deserves further research. Here, we showed that TiO2 NPs, widely used in nanomedicine, could trigger tumor-derived EVs with enhanced pro-metastatic capacity in vitro and in vivo. Mechanically, miR-301a-3p derived from NPs-elicited EVs could be delivered into vascular endothelial cells, which inhibited the expression of VEGFR2 and VE-cadherin by targeting S1PR1, leading to disrupt the tight junctions of vascular endothelial cells, thus to promote vascular permeability and angiogenesis, and induce the formation of pre-metastasis niches in vivo. This study emphasizes that it is urgent to consider the effect of NPs on EVs under long-term use conditions when designing nanodrugs for cancer treatment. Graphical Abstract

Abstract Purpose Owing to the complexity of cancer, a synergistic combination of chemotherapy and gene therapy can be a promising therapeutic strategy. This study aimed to use stem cell membrane (SCM)-camouflaged polydopamine nanoparticles for simultaneous delivery of curcumin (CUR) and siRNA-targeting STAT3 (CPDA/siSTAT3@SCM NPs) for osteosarcoma (OS). Methods Transmission electron microscopy, UV–Vis absorbance spectra, zeta potential, cell co-localization, and Coomassie bright blue staining were used to characterize CPDA/siSTAT3@SCM NPs constructed by the self-assembly method. Drug release, cellular uptake, cell proliferation, apoptosis, wound healing, and transwell assays were evaluated in vitro. The expression levels of epithelial–mesenchymal transition (EMT)- and apoptosis-related proteins were measured by western blotting. Furthermore, the biodistribution, antitumor efficacy, and biosafety of CPDA/siSTAT3@SCM NPs in an MG63 xenograft mouse model were evaluated. Results CPDA/siSTAT3@SCM NPs were successfully synthesized to deliver CUR and siRNA simultaneously, and they showed osteosarcoma-targeting ability. Furthermore, it showed high cellular uptake and excellent synergistic antitumor effects in vitro. CPDA/siSTAT3@SCM NPs suppressed OS cell proliferation, migration, invasion, and EMT progression, and promoted the apoptotic process. In tumor-bearing mice, the treatment with CPDA/siSTAT3@SCM NPs showed an excellent antitumor effect with no side effects in major organs. Conclusion This study revealed that CPDA/siSTAT3@SCM NPs can target drug delivery by biomimetic multifunctional nanoparticles to treat OS through chemo-gene combined therapy.

Abstract Background Inorganic nanocomposites especially Au nanostructures have exhibited outstanding physicochemical properties in biomedical fields. For further clinical applications on theranostics, especially drug delivery, numerous explorations of green and facile synthesis methods combining with pharmacoactive natural components have been investigated to construct safe and multifunctional bioactive Au nanoparticles (NPs). Ginsenoside Rh2 is protopanaxadiol type compound isolated from plants of genus Panax, with excellent anticancer effect and antioxidant activity. In this research, we prepared the novel Au nanoparticles using ginsenoside Rh2 as both reducing and stabilizing agents. Results The synthesized Au@ginsenoside Rh2 NPs were proved to exhibit desirable inhibitory effect on different cancer cell lines, which benefited from the inherent anticancer effect of the ginsenoside Rh2. Investigations in vitro indicated that Au@ginsenoside Rh2 NPs inhibited cell proliferation, cell migration and invasion, induced cell cycle arrest, enhanced the reactive oxygen species (ROS) generation, and regulated the protein expressions of caspase-3, 8, 9 to trigger cell apoptosis as well. Conclusions Because of the absence of toxic chemical surfactants, the eco-friendly synthesis method of Au NPs modified by natural phytochemicals avoided tedious separation and modification processes. On the other hand, Au@ginsenoside Rh2 NPs also improved water solubility and bioavailability of the hydrophobic drug ginsenoside Rh2. It broadened minds for preparation and application of traditional Chinese medicines (TCMs) modified metal nanoparticles and deserved further study.

Abstract Background Ureteral granulation tissue hemangiomas are rare benign vascular lesions, and they may be clinically asymptomatic or present with massive or recurrent hematuria. Sometimes hemangiomas are difficult to distinguish from malignant ureteral tumors, and most ureteral hemangiomas are confirmed by postoperative pathological examination. This article aims to present a case of granulation tissue-type hemangioma of the ureter and briefly review the current literature on this condition. Case presentation A 30-year-old male patient presented with complaints of painless macroscopic hematuria for 2 months. Computerized tomography of the urinary system showed that the upper 1/3 of the right ureter was occupied, and then the possibility of tumor lesions was considered. The urine cytology showed occasional nuclear abnormalities and many light-stained crystals in urine. Because of suspicious radiological and cytological findings, the patient underwent the right ureteroscopy and the laparoscopic right ureteral mass resection. The postoperative pathological report showed that it was a mesenchymal tumor. The morphological and immunohistochemical staining was consistent with that of hemangioma, tending to granulation tissue hemangioma. After surgery, the patient was in a good state and recovered well at the last follow-up. Conclusions Ureteral granulation tissue hemangiomas are an easily misdiagnosed disease. Intermittent painless hematuria is an important characteristic of this disease. Therefore, we suggest that unnecessary radical surgery can be avoided when clinicians consider the possibility of benign ureteral tumors during the evaluation.

IntroductionOsteosarcoma tumors are the most common malignant bone tumors in children and adolescents. Their treatment usually requires surgical removal of all detectable cancerous tissue and multidrug chemotherapy; however, the prognosis for patients with unresectable or recurrent osteosarcoma is unfavorable. To make chemotherapy safer and more effective for osteosarcoma patients, biomimetic nanoparticles (NPs) camouflaged by mesenchymal stem cell membranes (MSCMs) were synthesized to induce osteosarcoma cell apoptosis by co-delivering the anticancer drug doxorubicin hydrochloride(DOX) and a small interfering RNA (siRNA). Importantly, these NPs have high biocompatibility and tumor-homing ability. This study aimed to improve the efficacy of osteosarcoma therapy by using the synergistic combination of DOX and an siRNA targeting the apoptosis suppressor gene survivin.MethodsBiomimetic NPs (DOX/siSUR-PLGA@MSCM NPs) were synthesized by coloading DOX and survivin siRNA (siSUR) into poly (lactide-co-glycolide acid) (PLGA) via a double-emulsion solvent evaporation method. The NPs were camouflaged by MSCMs to deliver both DOX and survivin-targeting siRNA and characterized and evaluated in terms of cellular uptake, in vitro release, in vitro and in vivo antitumor effects, and biosafety.ResultsDOX/siSUR-PLGA@MSCM NPs had good tumor-homing ability due to the MSCMs modification. The drug-laden biomimetic NPs had good antitumor effects in homozygous MG63 tumor-bearing mice due to the synergistic effect of the drug combination.ConclusionDOX/siSUR-PLGA@MSCM NPs can show improved therapeutic effects in osteosarcoma patients due to the combination of a chemotherapeutic drug and gene therapy based on their good tumor targeting and biosafety.