Hädener Marianne, Gjuroski Ilche, Furrer Julien, Vermathen Martina
Department of Chemistry and Biochemistry, University of Bern , Freiestrasse 3, CH-3012 Bern, Switzerland.
J Phys Chem B. 2015 Sep 10;119(36):12117-28. doi: 10.1021/acs.jpcb.5b05761. Epub 2015 Aug 26.
Polyvinylpyrrolidone (PVP) can act as potential drug delivery vehicle for porphyrin-based photosensitizers in photodynamic therapy (PDT) to enhance their stability and prevent porphyrin self-association. In the present study the interactions of PVP (MW 10 kDa) were probed with five different derivatives of chlorin e6 (CE6) bearing either one of the amino acids serine, lysine, tyrosine or arginine, or monoamino-hexanoic acid as substituent. All derivatives of CE6 (xCE) formed aggregates of a similar structure in aqueous buffer in the millimolar range. In the presence of PVP monomerization of all xCE aggregates could be proved by (1)H NMR spectroscopy. xCE-PVP complex formation was confirmed by (1)H NMR T2 relaxation and diffusion ordered spectroscopy (DOSY). (1)H(1)H-NOESY data suggested that the xCE uptake into the PVP polymer matrix is governed by hydrophobic interactions. UV-vis absorption and fluorescence emission bands of xCE in the micromolar range revealed characteristic PVP-induced bathochromic shifts. The presented data point out the potential of PVP as carrier system for amphiphilic derivatives of chlorin e6. The capacity of PVP to monomerize xCE aggregates may enhance their efficiency as possible photosensitizers in PDT.
聚乙烯吡咯烷酮（PVP）可作为基于卟啉的光敏剂在光动力疗法（PDT）中的潜在药物递送载体，以增强其稳定性并防止卟啉自缔合。在本研究中，研究了分子量为10 kDa的PVP与二氢卟吩e6（CE6）的五种不同衍生物之间的相互作用，这些衍生物分别带有丝氨酸、赖氨酸、酪氨酸或精氨酸中的一种氨基酸，或单氨基己酸作为取代基。所有CE6衍生物（xCE）在毫摩尔范围内的水性缓冲液中形成结构相似的聚集体。通过（1）H NMR光谱法可以证明在PVP存在下所有xCE聚集体的单体化。通过（1）H NMR T2弛豫和扩散有序光谱法（DOSY）证实了xCE-PVP复合物的形成。（1）H（1）H-NOESY数据表明，xCE进入PVP聚合物基质是由疏水相互作用控制的。微摩尔范围内xCE的紫外可见吸收和荧光发射带显示出特征性的PVP诱导的红移。所呈现的数据指出了PVP作为二氢卟吩e6两亲衍生物载体系统的潜力。PVP使xCE聚集体单体化的能力可能会提高它们作为PDT中可能的光敏剂的效率。
