PO.CH01.04 · 化学
利用MUC1-适配体PBM-NP包封实现紫杉醇与和厚朴酚的靶向共递送以增强乳腺癌治疗
Targeted co-delivery of paclitaxel and honokiol using MUC1-aptamer PBM-NP encapsulation for enhanced breast cancer treatment
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
尽管乳腺癌（BrCa）治疗取得了进展，但因脱靶暴露于健康组织所致的剂量限制性毒性仍是有效治疗选择的重大障碍。本研究旨在通过将紫杉醇（PTX）和和厚朴酚（HNK）包封于行星球磨纳米颗粒（PBM-NP）中并包覆MUC1-适配体（S2.2）以实现靶向递送，从而增强其抗癌特性。采用计算机模拟（in silico）和体外方法评估PTX和HNK包封于适配体偶联PBM-NP（PTX-S2.2-PBM NP和HNK-S2.2-PBM NP）中的疗效。药代动力学模拟证明了在靶向MUC1治疗BrCa时联合使用PTX和HNK的潜在优势。组织微阵列分析证实MUC1在BrCa组织中的表达。研究发现MUC1组织表达具有分期依赖性，IV期BrCa组织中MUC1表达最高（93.9%），相比之下III期为36.5%、II期为11.3%、I期为0.4%。利用NHS偶联合成PTX-S2.2和HNK-S2.2 PBM-NP。采用动态光散射（DLS）、FTIR和HPLC对纳米颗粒进行表征。使用MTT和活/死细胞检测评估细胞毒性。DLS分析显示纳米颗粒具有理想的尺寸和zeta电位，适合体循环并改善治疗效果。通过FTIR和HPLC分析证实了成功的包封与偶联。细胞活力和增殖研究表明，单独使用PTX-S2.2-PBM NP和HNK-S2.2-PBM NP时，其细胞毒性分别与游离PTX和HNK相当或更强。二者联合使用时观察到协同效应。通过利用共聚物（PCL/PEG）和适配体偶联，与游离药物相比，PTX有望改善生物利用度并减少脱靶效应。基于这些发现，我们认为PTX-S2.2和HNK-S2.2 PBM NP可能是BrCa一种有前景的治疗选择。
查看英文原文 English abstract
Despite advancements in breast cancer (BrCa) treatments, dose-limiting toxicities caused by off-target exposure to healthy tissues remain a significant barrier to effective treatment options. This study aimed to enhance the anticancer properties of paclitaxel (PTX) and honokiol (HNK) through encapsulation in planetary-ball milled nanoparticles (PBM-NP) and coating with MUC1-aptamer (S2.2) for targeted delivery. Both in silico and in vitro methods were used to evaluate the efficacy of the encapsulation of PTX and HNK in aptamer-conjugated PBM-NPs (PTX-S2.2-PBM NP and HNK-S2.2-PBM NP). Pharmacokinetic simulations demonstrated the potential advantage of using PTX and HNK in combination while targeting MUC1 for BrCa treatment. Tissue microarray analysis confirmed the expression of MUC1 in BrCa tissues. It was found that MUC1 tissue expression was stage-dependent, with the highest MUC1 expression observed in Stage IV BrCa tissue (93.9%) compared to Stage III (36.5%), Stage II (11.3%), and Stage I (0.4%), respectively. NHS coupling was utilized to synthesize PTX-S2.2 and HNK-S2.2 PBM-NPs. Dynamic light scattering (DLS), FTIR, and HPLC were utilized to characterize the NPs. Cytotoxicity was assessed using MTT and Live/Dead cell assays. DLS analysis revealed that the NPs have a desirable size and zeta potential that are suitable for systemic circulation and improved therapeutic outcomes. Successful encapsulation and conjugation were confirmed through FTIR and HPLC analysis. Cell viability and proliferation studies demonstrated that PTX-S2.2-PBM NPs and HNK-S2.2-PBM NPs, when used individually, exhibited cytotoxicity comparable to or greater than that of free PTX and HNK, respectively. When combined, a synergistic effect was observed. Utilizing copolymers (PCL/PEG) and aptamer conjugation, PTX has the potential for improved bioavailability and reduced off-target effects compared to its free drug counterparts. Based on these findings, we believe that PTX-S2.2 and HNK-S2.2 PBM NP could represent a promising treatment option for BrCa.
利益披露 Disclosure
B. Kinnel, None..
A. K. Srivastava, None..
R. Singh, None.