背景:三阴性乳腺癌(TNBC)是一种侵袭性乳腺癌,转移率高,总体生存时间差,对靶向治疗反应低。为了提高治疗效果,克服TNBC治疗的耐药性,在这里,我们开发了癌细胞膜包被的氧气递送纳米探针,CCm-HSA-ICG-PFTBA,这可以改善肿瘤部位的缺氧并增强光动力疗法(PDT)的疗效,从而缓解TNBC异种移植物中的肿瘤生长。
结果:CCm-HSA-ICG-PFTBA的大小为131.3±1.08nm。CCm-HSA-ICG-PFTBA组的体外1O2和ROS浓度均显著高于其他组(P<0.001)。体内荧光成像显示,最佳时间窗口是在注射CCm-HSA-ICG-PFTBA后24小时。体内18F-FMISOPET成像和离体免疫荧光染色结果表明,注射CCm-HSA-ICG-PFTBA后24h肿瘤缺氧明显改善。对于体内PDT治疗,NIRCCm-HSA-ICG-PFTBA组的肿瘤体积和重量均在所有组中最小,与未治疗组相比显着降低(P<0.01)。注射CCm-HSA-ICG-PFTBA至14天未观察到明显的生物毒性。
结论:利用全氟化碳(PFC)的高氧溶解度和癌细胞膜的同源靶向能力,CCm-HSA-ICG-PFTBA可以靶向肿瘤组织,减轻肿瘤微环境的缺氧,并增强TNBC异种移植物中的PDT功效。此外,HSA,ICG,PFC都是FDA批准的材料,这使得纳米颗粒具有高度的生物相容性,并增强了在TNBC患者治疗中临床转化的潜力。
BACKGROUND: Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm-HSA-ICG-PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts.
RESULTS: The size of the CCm-HSA-ICG-PFTBA was 131.3 ± 1.08 nm. The in vitro 1O2 and ROS concentrations of the CCm-HSA-ICG-PFTBA group were both significantly higher than those of the other groups (P < 0.001). In vivo fluorescence imaging revealed that the best time window was at 24 h post-injection of the CCm-HSA-ICG-PFTBA. Both in vivo 18F-FMISO PET imaging and ex vivo immunofluorescence staining results exhibited that the tumor hypoxia was significantly improved at 24 h post-injection of the CCm-HSA-ICG-PFTBA. For in vivo PDT treatment, the tumor volume and weight of the CCm-HSA-ICG-PFTBA with NIR group were both the smallest among all the groups and significantly decreased compared to the untreated group (P < 0.01). No obvious biotoxicity was observed by the injection of CCm-HSA-ICG-PFTBA till 14 days.
CONCLUSIONS: By using the high oxygen solubility of perfluorocarbon (PFC) and the homologous targeting ability of cancer cell membranes, CCm-HSA-ICG-PFTBA can target tumor tissues, mitigate the hypoxia of the tumor microenvironment, and enhance the PDT efficacy in TNBC xenografts. Furthermore, the HSA, ICG, and PFC are all FDA-approved materials, which render the nanoparticles highly biocompatible and enhance the potential for clinical translation in the treatment of TNBC patients.