Carrier-free multifunctional nanomedicine for intraperitoneal disseminated ovarian cancer therapy

Abstract

Background Ovarian cancer is the most lethal gynecological cancer which is characterized by extensive peritoneal implantation metastasis and malignant ascites. Despite advances in diagnosis and treatment in recent years, the five-year survival rate is only 25–30%. Therefore, developing multifunctional nanomedicine with abilities of promoting apoptosis and inhibiting migration on tumor cells would be a promising strategy to improve the antitumor effect. Methods and results In this study, we developed a novel ACaT nanomedicine composed of alendronate, calcium ions and cyclin-dependent kinase 7 (CDK7) inhibitor THZ1. With the average size of 164 nm and zeta potential of 12.4 mV, the spherical ACaT nanoparticles were selectively internalized by tumor cells and effectively accumulated in the tumor site. Results of RNA-sequencing and in vitro experiments showed that ACaT promoted tumor cell apoptosis and inhibited tumor cell migration by arresting the cell cycle, increasing ROS and affecting calcium homeostasis. Weekly intraperitoneally administered of ACaT for 8 cycles significantly inhibited the growth of tumor and prolonged the survival of intraperitoneal xenograft mice. Conclusion In summary, this study presents a new self-assembly nanomedicine with favorable tumor targeting, antitumor activity and good biocompatibility, providing a novel therapeutic strategy for advanced ovarian cancer. Graphical Abstract

Role of Phosphorus-Containing Molecules on the Formation of Nano-Sized Calcium Phosphate for Bone Therapy

“…As shown in Supplementary Figure S2 , the XRD patterns of CaP/Zda matches those of calcium–Zda complexes extracted from cif data provided by Freire et al (2010) , indicating that CaP/Zda is a complex of calcium and Zda. According to the simulation results, Adn and Zda have close binding energy with calcium, while Adn decreased the crystallinity of CaP, which is also extensively reported ( Huang et al, 2022 ), and Zda and calcium formed a complex with a higher crystallinity. CaP/Ada and CaP/Zda may have different atomic arrangements due to the different spatial configuration of Adn and Zda.…”

“…The nanocomplex can release phosphorus-containing drugs with degradation, as CaP is pH sensitive ( Gou et al, 2016 ; Mi et al, 2016 ). Hence, Adn and Zda can realize controlled release under acid conditions( Huang et al, 2022 ). Since the bisphosphonates are reported to inactivate human epidermal growth factor receptors (human EGFR or HER) to perform antitumor actions ( Yuen et al, 2014 ), CaP/Adn and CaP/Zda can be considered to be promising drug delivery systems for osteosarcoma therapy.…”

microRNA-324-3p suppresses the aggressive ovarian cancer by targeting WNK2/RAS pathway

“…Primary cytoreductive surgery followed by chemotherapy is the commonly used treatment for OC [ 3 ]. Despite continuous development in surgical skills and chemotherapy techniques, the 5-year survival rate of OC remains below 40% [ 4 ]. Unveiling OC progression mechanism and developing new therapeutic targets is crucial for improving patient outcomes.…”

Intraperitoneal administration of thermosensitive hydrogel Co-loaded with norcantharidin nanoparticles and oxaliplatin inhibits malignant ascites of hepatocellular carcinoma

“…The presence of malignant ascites not only shortens the median survival time of cancer patients, but also aggravates the clinical symptoms and worsens their quality of life. IP chemotherapy, wherein drugs are injected directly into the abdominal cavity, is an effective treatment against malignant ascites since it achieves high local drug concentrations with low systemic toxicity (Wen et al, 2020 ; Huang et al, 2022 ). Moreover, the combination of drugs with different targets and mechanisms of action may have a synergistic effect against tumor cells and thus improve treatment outcomes (Gong et al, 2012 ).…”