Research Insight - Development of calcium phosphate nanoparticles for enhancing the chemotherapy effect of ovarian cancer
2023-08-04 13:33:52
The team published a paper titled ”Engineering Chemotherapeutic-Augmented Calcium Phosphate Nanoparticles for Treatment of Intraperitoneal Disseminated Ovarian Cancer” in ACS Applied Materials & Interfaces (IF=9.229, Q1).
Our AniView series multi-mode animal in vivo imaging system was used in the experiment of in vivo imaging of CaPO/DiR labeled mice and SKOV3-Luc mice.
Ovarian cancer is one of the common malignant tumors in gynecology. Intraperitoneal chemotherapy has been proven to be an effective clinical treatment for disseminated gastrointestinal and gynecological cancer, which can increase the exposure of therapeutic drugs to cancer cells and reduce systemic toxicity.
However, patients with advanced ovarian cancer are prone to recurrence after chemotherapy. When combating tumor heterogeneity and drug resistance, multi-mechanism-induced tumor cell death appears to be superior to a single targeted pathway.
Doxorubicin (DOX) is a second-line agent in chemotherapy for platinum-based resistance to ovarian cancer. It can inhibit tumor progression by inhibiting DNA replication. It has also been proved that the drug can destroy the balance of redox status in cells and induce endoplasmic reticulum stress. However, due to the lack of selectivity of drugs towards tumors, high doses of DOX are usually required to achieve effective chemotherapy effects, and even local application of drugs can cause systemic side effects.
In this study, Chen Yu's team constructed DOX-loaded nano calcium phosphate (CaPO) through in-situ mineralization, and further modified the Arg- Gory - Asp (RGD) sequence on the surface of CaPO, targeting the highly expressed Integrin in ovarian tumors αvβ3 to achieved efficient treatment of ovarian cancer. These reasonably designed RGD-CaPO/DOX NPs can be effectively engulfed by the human ovarian cancer cell line SKOV3, releasing DOX and Ca2+. DOX increases the level of intracellular reactive oxygen species (ROS), induces Endoplasmic reticulum stress, further promotes the imbalance of Ca2+homeostasis, and ultimately leads to apoptosis of tumor cells. These different calcium-involved NPs provide an effective synergistic treatment for intraperitoneal disseminated ovarian cancer, with negligible biological toxicity.
△ Figure 1 Research Strategy for RGD CaPO/DOX Systems
Figure 2 In vivo biological distributions of CaPO/DiR and RGD CaPO/DiR NPs
△ Figure 3 Bioluminescence images of SKOV3 Luc tumor bearing mice treated with PBS and RGD CaPO (50 mg kg-1) respectivelyThis study designed and const
This study designed and constructed a multifunctional RGD-CaPO/DOX system to achieve effective synergistic treatment of intraperitoneal disseminated ovarian cancer. The RGD-CaPO/DOX system exhibits time-dependent cellular absorption, pH-sensitive degradation, and in vitro drug release. In vivo fluorescence imaging shows that RGD-CaPO NPs have specific accumulation in tumors, while they are almost invisible in other organs, clearly indicating that the drug has significant tumor selectivity. In the SKOV3 tumor-bearing mouse model, intraperitoneal injection of RGD-CaPO/DOX effectively inhibited tumor progression, and the average survival time of the mice was extended from 29 days to 59 days.
In summary, Yu Chen team's research provides an effective chemotherapy enhancement strategy for the treatment of ovarian cancer by combining calcium-doped nanomedicine and ROS-induced chemotherapy drug loading.
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Reference:
Engineering Chemotherapeutic-Augmented Calcium Phosphate Nanoparticles for Treatment of Intraperitoneal Disseminated Ovarian Cancer
Miaojuan Qiu, Junzong Chen, Xiuyu Huang, Binbin Li, Shiqiang Zhang, Peng Liu, Qiang Wang, Zhi Rong Qian, Yihang Pan, Yu Chen, and Jing Zhao
ACS Applied Materials & Interfaces 2022 14 (19), 21954-21965 DOI: 10.1021/acsami.2c02552