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Two-Photon Photosensitizer–Polymer Conjugates for Combined Cancer Cell Death Induction and Two-Photon Fluorescence Imaging: Structure/Photodynamic Therapy Efficiency Relationship
Biomacromolecules ( IF 5.5 ) Pub Date : 2017-11-10 00:00:00 , DOI: 10.1021/acs.biomac.7b01090 Cristina Cepraga 1, 2, 3 , Sophie Marotte 1, 4 , Edna Ben Daoud 1, 4 , Arnaud Favier 1, 2 , Pierre-Henri Lanoë 3 , Cyrille Monnereau 3 , Patrice Baldeck 3 , Chantal Andraud 3 , Jacqueline Marvel 4 , Marie-Thérèse Charreyre 1, 2 , Yann Leverrier 4
Biomacromolecules ( IF 5.5 ) Pub Date : 2017-11-10 00:00:00 , DOI: 10.1021/acs.biomac.7b01090 Cristina Cepraga 1, 2, 3 , Sophie Marotte 1, 4 , Edna Ben Daoud 1, 4 , Arnaud Favier 1, 2 , Pierre-Henri Lanoë 3 , Cyrille Monnereau 3 , Patrice Baldeck 3 , Chantal Andraud 3 , Jacqueline Marvel 4 , Marie-Thérèse Charreyre 1, 2 , Yann Leverrier 4
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One of the challenges of photodynamic therapy is to increase the penetration depth of light irradiation in the tumor tissues. Although two-photon excitation strategies have been developed, the two-photon absorption cross sections of clinically used photosensitizers are generally low (below 300 GM). Besides, photosensitizers with high cross section values are often non-water-soluble. In this research work, a whole family of photosensitizer–polymer conjugates was synthesized via the covalent binding of a photosensitizer with a relatively high cross section along a biocompatible copolymer chain. The resulting photosensitizer–polymer conjugates were water-soluble and could be imaged in cellulo by two-photon microscopy thanks to their high two-photon absorption cross sections (up to 2600 GM in water, in the NIR range). In order to explore the structure/photodynamic activity relationship of such macromolecular photosensitizers, the influence of the polymer size, photosensitizer density, and presence of charges along the polymer backbone was investigated (neutral, anionic, cationic, and zwitterionic conjugates were compared). The macromolecular photosensitizers were not cytotoxic in the absence of light irradiation. Their kinetics of cellular uptake in the B16–F10 melanoma cell line were followed by flow cytometry over 24 h. The efficiency of cell death upon photoactivation was found to be highly correlated to the cellular uptake in turn correlated to the global charge of the macromolecular photosensitizer which appeared as the determining structural parameter.
中文翻译：
两光子光敏剂-聚合物共轭组合的癌细胞死亡诱导和两光子荧光成像：结构/光动力治疗效率的关系。
光动力疗法的挑战之一是增加光照射在肿瘤组织中的穿透深度。尽管已经开发了双光子激发策略，但是临床上使用的光敏剂的双光子吸收截面通常较低（低于300 GM）。此外，具有高横截面值的光敏剂通常是非水溶性的。在这项研究工作中，通过沿生物相容性共聚物链具有相对较高横截面的光敏剂的共价结合，合成了整个光敏剂-聚合物共轭物系列。所得的光敏剂-聚合物共轭物是水溶性的，可以在纤维素中成像通过双光子显微镜进行分析，这要归功于其具有很高的双光子吸收截面（在水中，NIR范围内高达2600 GM）。为了探索此类大分子光敏剂的结构/光动力活性关系，研究了聚合物尺寸，光敏剂密度和沿聚合物主链的电荷存在的影响（比较了中性，阴离子，阳离子和两性离子共轭物）。在没有光照射的情况下，大分子光敏剂没有细胞毒性。他们在B16–F10黑色素瘤细胞系中摄取细胞的动力学，然后在24小时内进行流式细胞术。
更新日期：2017-11-11
中文翻译：
两光子光敏剂-聚合物共轭组合的癌细胞死亡诱导和两光子荧光成像：结构/光动力治疗效率的关系。
光动力疗法的挑战之一是增加光照射在肿瘤组织中的穿透深度。尽管已经开发了双光子激发策略，但是临床上使用的光敏剂的双光子吸收截面通常较低（低于300 GM）。此外，具有高横截面值的光敏剂通常是非水溶性的。在这项研究工作中，通过沿生物相容性共聚物链具有相对较高横截面的光敏剂的共价结合，合成了整个光敏剂-聚合物共轭物系列。所得的光敏剂-聚合物共轭物是水溶性的，可以在纤维素中成像通过双光子显微镜进行分析，这要归功于其具有很高的双光子吸收截面（在水中，NIR范围内高达2600 GM）。为了探索此类大分子光敏剂的结构/光动力活性关系，研究了聚合物尺寸，光敏剂密度和沿聚合物主链的电荷存在的影响（比较了中性，阴离子，阳离子和两性离子共轭物）。在没有光照射的情况下，大分子光敏剂没有细胞毒性。他们在B16–F10黑色素瘤细胞系中摄取细胞的动力学，然后在24小时内进行流式细胞术。
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