Nicosia Angelo, La Perna Giuseppe, Cucci Lorena Maria, Satriano Cristina, Mineo Placido
Polymer Laboratory, Department of Chemical Sciences, University of Catania, Viale A. Doria 6, I-95125 Catania, Italy.
NanoHybrid Biointerfaces Lab (NHBIL), Department of Chemical Sciences, University of Catania, Viale A. Doria 6, I-95125 Catania, Italy.
Polymers (Basel). 2022 Oct 14;14(20):4329. doi: 10.3390/polym14204329.
Polymer-based systems have been demonstrated in novel therapeutic and diagnostic (theranostic) treatments for cancer and other diseases. Polymers provide a useful scaffold to develop multifunctional nanosystems that combine various beneficial properties such as drug delivery, bioavailability, and photosensitivity. For example, to provide passive tumour targeting of small drug molecules, polymers have been used to modify and functionalise the surface of water-insoluble drugs. This approach also allows the reduction of adverse side effects, such as retinoids. However, multifunctional polymer conjugates containing several moieties with distinct features have not been investigated in depth. This report describes the development of a one-pot approach to produce a novel multifunctional polymer conjugate. As a proof of concept, we synthesised polyvinyl alcohol (PVA) covalently conjugated with rhodamine B (a tracking agent), folic acid (a targeting agent), and all-trans retinoic acid (ATRA, a drug). The obtained polymer (PVA@RhodFR) was characterised by MALDI-TOF mass spectrometry, gel permeation chromatography, thermal analysis, dynamic light-scattering, NMR, UV-Vis, and fluorescence spectroscopy. Finally, to evaluate the efficiency of the multifunctional polymer conjugate, cellular differentiation treatments were performed on the neuroblastoma SH-SY5Y cell line. In comparison with standard ATRA-based conditions used to promote cell differentiation, the results revealed the high capability of the new PVA@RhodFR to induce neuroblastoma cells differentiation, even with a short incubation time and low ATRA concentration.
基于聚合物的系统已被应用于癌症和其他疾病的新型治疗与诊断(治疗诊断一体化)治疗中。聚合物为开发多功能纳米系统提供了有用的支架,这些系统结合了各种有益特性,如药物递送、生物利用度和光敏性。例如,为了实现对小药物分子的被动肿瘤靶向,聚合物已被用于修饰水不溶性药物的表面并使其功能化。这种方法还可以减少不良副作用,如维甲酸类药物的副作用。然而,含有几个具有不同特征部分的多功能聚合物缀合物尚未得到深入研究。本报告描述了一种一锅法制备新型多功能聚合物缀合物的方法。作为概念验证,我们合成了与罗丹明B(一种追踪剂)、叶酸(一种靶向剂)和全反式维甲酸(ATRA,一种药物)共价缀合的聚乙烯醇(PVA)。通过基质辅助激光解吸电离飞行时间质谱、凝胶渗透色谱、热分析、动态光散射、核磁共振、紫外可见光谱和荧光光谱对所得聚合物(PVA@RhodFR)进行了表征。最后,为了评估多功能聚合物缀合物的效率,对神经母细胞瘤SH-SY5Y细胞系进行了细胞分化处理。与用于促进细胞分化的基于标准ATRA的条件相比,结果表明新型PVA@RhodFR即使在短孵育时间和低ATRA浓度下也具有很高的诱导神经母细胞瘤细胞分化的能力。