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α-乳白蛋白信使核糖核酸脂质纳米颗粒联合手术对三阴性乳腺癌具有抗肿瘤作用

α-Lactalbumin mRNA-LNP Evokes an Anti-Tumor Effect Combined with Surgery in Triple-Negative Breast Cancer.

作者信息

He Yun-Ru, Xia Heng, Yun Peng, Xu Yuandong, Ma Winson M J, Xiao Ze-Xiu, Zha Gao-Feng

机构信息

Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital, Sun Yat-sen University, No. 628, Zhenyuan Road, Guangming District, Shenzhen 518107, China.

Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, No. 628, Zhenyuan Road, Guangming District, Shenzhen 518107, China.

出版信息

Pharmaceutics. 2024 Jul 14;16(7):940. doi: 10.3390/pharmaceutics16070940.

Abstract

Triple-negative breast cancer (TNBC) has been considered a huge clinical unmet need due to its aggressive progression and highly frequent metastasis. mRNA therapeutics supply a potential and versatile immunotherapy of oncology treatment. Here, we developed α-lactalbumin mRNA-lipid nanoparticles (α-LNP) as a potential therapeutical strategy for TNBC. The α-LNP induced the specific IgG antibodies and activated IFN γ-secreting-T cells in vivo. Additionally, the safety of α-LNP also had been demonstrated in vivo. When vaccinated prior to tumor implantation, α-LNP showed a preventive effect against 4T1 tumor growth and extended the survival of the tumor model by activating the memory immune responses. Furthermore, α-LNP administration in combination with surgical removal of neoplasm effectively inhibited the progression and metastasis in the TNBC model. Taken together, our results indicate that the α-LNP vaccine is a promising novel treatment for both therapeutics and prophylactics in TNBC.

摘要

三阴性乳腺癌(TNBC)因其侵袭性进展和高转移率,一直被视为临床上面临的重大未满足需求。信使核糖核酸(mRNA)疗法为肿瘤治疗提供了一种潜在的通用免疫疗法。在此,我们开发了α-乳白蛋白信使核糖核酸-脂质纳米颗粒(α-LNP),作为三阴性乳腺癌的一种潜在治疗策略。α-LNP在体内诱导产生特异性IgG抗体并激活分泌干扰素γ的T细胞。此外,α-LNP的安全性也已在体内得到证实。在肿瘤植入前进行接种时,α-LNP对4T1肿瘤生长显示出预防作用,并通过激活记忆免疫反应延长了肿瘤模型的生存期。此外,α-LNP给药联合手术切除肿瘤可有效抑制三阴性乳腺癌模型中的肿瘤进展和转移。综上所述,我们的结果表明,α-LNP疫苗在三阴性乳腺癌的治疗和预防方面都是一种很有前景的新型治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d36/11279974/2b5bb48566c5/pharmaceutics-16-00940-g001.jpg

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