研究动态
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应用生物工程的酵母液泡,通过与TLR2结合的肽(VacT2BP)诱导一个促炎反应,作为为达诺霉素传递的药物载体。

Inducing a Proinflammatory Response with Bioengineered Yeast Vacuoles with TLR2-Binding Peptides (VacT2BP) as a Drug Carrier for Daunorubicin Delivery.

发表日期:2023 Aug 24
作者: Wooil Choi, Woo-Ri Shin, Yang-Hoon Kim, Jiho Min
来源: Cellular & Molecular Immunology

摘要:

在癌症治疗中,免疫佐剂在免疫激活中发挥作用,而源自微生物的佐剂已得到应用。本研究中,我们提出使用从重组酵母中衍生出的具有急性髓系白血病(AML)特异性的生物工程液泡并在其表面带有TLR-2结合肽(VacT2BP)的方法,以诱导促炎反应作为一种双功能的纳米材料用于多柔比星(DNR)传递。我们的结果表明,纳米级别的、孤立的VacT2BP可诱导HL-60细胞特异性的DNR传递和凋亡。此外,我们观察到DNR@VacT2BP从凋亡的HL-60细胞中选择性释放高迁移率组蛋白1。我们得出结论,DNR@VacT2BP表现出靶向选择性,VacT2BP载体抑制了无选择性的损伤相关分子模式(DAMP)的发生。DNR@VacT2BP的治疗效果在AML异种移植小鼠中得到验证,肿瘤生长抑制率约为82%。在药物传递后,凋亡细胞和具有残留VacT2BP的DAMPs(apopDNR@VacT2BP)上调了巨噬细胞的促炎免疫反应。此外,apopDNR@VacT2BP增强了巨噬细胞的吞噬活性。通过apopDNR@VacT2BP刺激的巨噬细胞抑制了约40%的癌细胞增殖。总之,我们的结果表明,具有靶向特异性肽的双功能液泡可以成为有选择性的药物传递和构建免疫环境以对抗癌症的潜在策略,从而改善预后。
Immune adjuvants have roles in immune activation for cancer therapy, and adjuvants derived from microbes have been applied. In this study, we propose the use of bioengineered vacuoles, derived from recombinant yeast with acute myeloid leukemia (AML) specificity and having a TLR-2-binding peptide (VacT2BP) on their surface, to induce a proinflammatory response as a dual-function nanomaterial for daunorubicin (DNR) delivery. Our results demonstrate that nanosized, isolated VacT2BP induced HL-60 cell-specific DNR delivery and apoptosis. Furthermore, we observed the selective release of high-mobility group box 1 from apoptotic HL-60 cells by DNR@VacT2BP. We concluded that DNR@VacT2BP exhibited target selectivity, and the indiscriminate occurrence of damage-associated molecular patterns (DAMPs) was inhibited by the VacT2BP carrier. The therapeutic efficacy of DNR@VacT2BP was confirmed in AML xenograft mice, with about 82% tumor growth inhibition. Following drug delivery, apoptotic cells and DAMPs with residual VacT2BP (apopDNR@VacT2BP) upregulated the proinflammatory immune response of macrophages. In addition, apopDNR@VacT2BP enhanced phagocytosis activity. Macrophages stimulated by apopDNR@VacT2BP suppressed cancer proliferation by about 40%. In summary, our results suggest that dual-functional vacuoles with a target-specific peptide can be a potential strategy for selective drug delivery and construction of an immune environment to fight cancer, thereby improving prognosis.