Abstract:Abstract. Osteosarcoma (OS) is the most common malignant bone tumour and is considered to be a disease caused by a dysfunction in differentiation. Bone morphogenetic protein 9 (BMP9) is the most potent osteogenic factor in mesenchymal stem cells, but it cannot induce osteogenic differentiation in OS cells; this might be one of the determinants in the pathogenesis of OS. All-trans retinoic acid (ATRA) can induce osteogenic differentiation of OS cells and potentiate BMP9-induced osteogenesis in preadipocytes. Ho… Show more
“…[11][12][13][14] Furthermore, it has been reported that ATRA also promoted osteogenic differentiation of different subtypes of OS cells both in vitro and in vivo. [15,16] Since ATRA (a vitamin A derivative) initially existed in the human body, it possesses negligible cytotoxic. [17] These results suggested ATRA was a potential and promising weapon against OS.…”
Osteosarcoma (OS) is the most frequent osseous neoplasm among young people aged 10–20. Currently, the leading treatment for osteosarcoma is a combination of surgery and chemotherapy. However, the mortality remains high due to chemoresistance, metastasis, and recurrence, attributing to the existence of cancer stem cells (CSCs) as reported. To target CSCs, differentiation therapy attracts increasing attention, inducing CSCs to bulk tumor cells with elevated reactive oxygen species (ROS) levels and less chemoresistance. Moreover, increasing studies have implied that ferroptosis is a promising approach to eliminating cancer cells through eliciting oxidative damage and subsequent apoptosis, effectively bypassing chemoresistance. Here, a cancer‐cell‐membrane‐decorated biocompatible formulation (GA‐Fe@CMRALi liposome) is constructed to combat OS efficiently by combining distinct differentiation and ferroptosis therapies through magnified ROS‐triggered ferroptosis and apoptosis with homologous target capability to tumor sites. The combinational approach exhibited favorable therapeutic efficacy against OS in vitro and in vivo. Impressively, the potential mechanisms are revealed by mRNA sequencing. This study provides a tactical design and typical paradigm of the synergized differentiation and ferroptosis therapies to combat heterogeneous OS.
“…[11][12][13][14] Furthermore, it has been reported that ATRA also promoted osteogenic differentiation of different subtypes of OS cells both in vitro and in vivo. [15,16] Since ATRA (a vitamin A derivative) initially existed in the human body, it possesses negligible cytotoxic. [17] These results suggested ATRA was a potential and promising weapon against OS.…”
Osteosarcoma (OS) is the most frequent osseous neoplasm among young people aged 10–20. Currently, the leading treatment for osteosarcoma is a combination of surgery and chemotherapy. However, the mortality remains high due to chemoresistance, metastasis, and recurrence, attributing to the existence of cancer stem cells (CSCs) as reported. To target CSCs, differentiation therapy attracts increasing attention, inducing CSCs to bulk tumor cells with elevated reactive oxygen species (ROS) levels and less chemoresistance. Moreover, increasing studies have implied that ferroptosis is a promising approach to eliminating cancer cells through eliciting oxidative damage and subsequent apoptosis, effectively bypassing chemoresistance. Here, a cancer‐cell‐membrane‐decorated biocompatible formulation (GA‐Fe@CMRALi liposome) is constructed to combat OS efficiently by combining distinct differentiation and ferroptosis therapies through magnified ROS‐triggered ferroptosis and apoptosis with homologous target capability to tumor sites. The combinational approach exhibited favorable therapeutic efficacy against OS in vitro and in vivo. Impressively, the potential mechanisms are revealed by mRNA sequencing. This study provides a tactical design and typical paradigm of the synergized differentiation and ferroptosis therapies to combat heterogeneous OS.
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