Fabrication of epidermal growth factor functionalized polymeric poly(lactic-co-glycolic acid) nanoparticles loaded SN-38 and perfluorocarbon for treatment and care: investigation of antiproliferative effects and apoptosis in cervical cancer cells

Lu Zheng, Jiyan Ma, Jie Zhao
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Abstract

Abstract Patients with cervical cancer have a significant risk of tumor recurrence and metastasis. The discovery of effective treatments for cervical cancer is urgently needed. Poly(lactic-co-glycolic acid) (PLGA) was recently discovered to offer a promising therapeutic drug carrier. Hence, we developed dual-loaded PLGA nanoparticles (NPs) as a drug carrier to combat this problem with current chemotherapeutic drugs for cervical cancer. We engineered PLGA NPs with epidermal growth factor (EGF) functionalization and co-loaded them with SN-38 and perfluorocarbon (PC) to treat cervical cancer selectively. Cell counting kit-8 test results reveal that newly fabricated NPs effectively induce cell proliferation in cervical cancer cells. Further, flow cytometry, Hoechst 33342 staining and acridine orange and propidium iodide staining were used to determine the apoptosis of SN38/PC@EGF-PLGA NPs in HeLa and CaSki cells. And the release was pH-dependent when tested in vitro. Cervical cancer cells took up targeted SN38/PC@EGF-PLGA NPs at a greater rate than untargeted NPs. Furthermore, HeLa and CaSki cells were more sensitive to apoptosis induction and cell viability suppression when exposed to SN38/PC@EGF-PLGA NPs than nontargeted NPs. The findings of this study improve the exploration of SN38/PC@EGF-PLGA NPs in the new development of effective drug candidates for highly invasive cervical cancer in future. Graphical Abstract
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负载SN-38和全氟碳的表皮生长因子功能化聚合物聚乳酸-羟基乙酸纳米颗粒的制备及其治疗和护理:宫颈癌细胞的抗增殖作用和凋亡研究
宫颈癌患者有明显的肿瘤复发和转移风险。迫切需要发现宫颈癌的有效治疗方法。聚乳酸-羟基乙酸(PLGA)是近年来发现的一种很有前途的治疗药物载体。因此,我们开发了双负载PLGA纳米颗粒(NPs)作为药物载体,以解决当前宫颈癌化疗药物的这一问题。我们设计了表皮生长因子(EGF)功能化的PLGA NPs,并将其与SN-38和全氟碳化合物(PC)共载,以选择性地治疗宫颈癌。细胞计数试剂盒-8检测结果显示,新制备的NPs能有效诱导宫颈癌细胞增殖。采用流式细胞术、Hoechst 33342染色、吖啶橙和碘化丙啶染色检测HeLa和CaSki细胞中SN38/PC@EGF-PLGA NPs的凋亡情况。在体外测试时,释放是ph依赖性的。宫颈癌细胞对靶向SN38/PC@EGF-PLGA NPs的吸收率高于非靶向NPs。此外,当暴露于SN38/PC@EGF-PLGA NPs时,HeLa和CaSki细胞对凋亡诱导和细胞活力抑制的敏感性高于非靶向NPs。本研究结果为今后在高侵袭性宫颈癌有效候选药物的新开发中探索SN38/PC@EGF-PLGA NPs提供了基础。图形抽象
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