Choi Moon Jung, Lee Yeon Kyung, Choi Kang Chan, Lee Do Hyun, Jeong Hwa Yeon, Kang Seong Jae, Kim Min Woo, You Young Myoung, Im Chan Su, Lee Tae Sup, Park Yong Serk
Department of Biomedical Laboratory Science, Yonsei University, Wonju 26493, Republic of Korea.
Division of RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul 01812, Republic of Korea.
Pharmaceutics. 2023 Jan 20;15(2):350. doi: 10.3390/pharmaceutics15020350.
Triple-negative breast cancer (TNBC) cells do not contain various receptors for targeted treatment, a reason behind the poor prognosis of this disease. In this study, biocompatible theranostic erythrocyte-derived nanoparticles (EDNs) were developed and evaluated for effective early diagnosis and treatment of TNBC. The anti-cancer drug, doxorubicin (DOX), was encapsulated into the EDNs and diagnostic quantum dots (QDs) were incorporated into the lipid bilayers of EDNs for tumor bio-imaging. Then, anti-epidermal growth factor receptor (EGFR) antibody molecules were conjugated to the surface of EDNs for TNBC targeting (iEDNs). According to the confocal microscopic analyses and biodistribution assay, iEDNs showed a higher accumulation in EGFR-positive MDA-MB-231 cancers in vitro as well as in vivo, compared to untargeted EDNs. iEDNs containing doxorubicin (iEDNs-DOX) showed a stronger inhibition of target tumor growth than untargeted ones. The resulting anti-EGFR iEDNs exhibited strong biocompatibility, prolonged blood circulation, and efficient targeting of TNBC in mice. Therefore, iEDNs may be used as potential TNBC-targeted co-delivery systems for therapeutics and diagnostics.
三阴性乳腺癌(TNBC)细胞不含有用于靶向治疗的各种受体,这是该疾病预后不良的一个原因。在本研究中,开发了生物相容性治疗诊断红细胞衍生纳米颗粒(EDNs),并对其用于TNBC的有效早期诊断和治疗进行了评估。将抗癌药物阿霉素(DOX)封装到EDNs中,并将诊断性量子点(QDs)掺入EDNs的脂质双层中用于肿瘤生物成像。然后,将抗表皮生长因子受体(EGFR)抗体分子偶联到EDNs表面用于TNBC靶向(iEDNs)。根据共聚焦显微镜分析和生物分布测定,与未靶向的EDNs相比,iEDNs在体外和体内的EGFR阳性MDA-MB-231癌中均表现出更高的积累。含有阿霉素的iEDNs(iEDNs-DOX)对靶肿瘤生长的抑制作用比未靶向的iEDNs更强。所得的抗EGFR iEDNs在小鼠中表现出很强的生物相容性、延长的血液循环以及对TNBC的有效靶向。因此,iEDNs可作为潜在的用于治疗和诊断的TNBC靶向共递送系统。