Development of next generation of photosensitizer for fluorescent imaging and photodynamic therapy of cancer

我们设计并合成了一类新的罗丹明染料，共轭体系，命名为3 '，3“-双（氧代螺异苯并呋喃）-3，7-双（二乙基氨基）苯并吡喃氧杂蒽（ABPX 01）染料。在这项研究中，进行了调查，以揭示ABPX 01的化学物种，颜色和荧光发射在不同的解决方案之间的关系。ABPX 01有多种形式：无色的螺内酯形式（ABPX 01 ^0）;以及有色的单阳离子形式（ABPX 01 H ^+）和双阳离子形式（ABPX 01 H_2 ^<2+>）。ABPX_（01）H_2 ^<2+>为红色荧光物质。详细的光谱和电子显微镜研究假设，ABPX 01 H_2 ^<2+>形成的离子与Cl^-在HCl水溶液中作为抗衡阴离子缔合，ABPX 01盐酸盐纳米和亚微米级的胶体聚集体具有荧光发射。在荧光成像中的良好性能需要大的荧光量子产率，以及标记物在水溶性介质中的溶解度。我们设计并合成了新的ABPX衍生物，其中氨基被纳入刚性六元环。ABPX 101 H_2 ^<2+>、ABPX 102 H_2 ^<2+>和ABPX 103 H_2 ^<2+>的相对荧光量子产率相对于ABPX 01 H_2 ^<2 +>显著增加。所有ABPX衍生物都具有良好的双峰荧光发射光谱，其发射光谱范围很宽，包括红光和近红外区。ABPX染料的固有溶解性有利于作为荧光成像和光动力学治疗的光敏剂。

We have designed and synthesized a new class of rhodamine dyes with an extended ?-conjugated system, named 3’,3’’-bis(oxospiroisobenzofuran)-3,7-bis(diethylamino)benzopyrano-xanthene (ABPX01) dye. In this study, the investigations were carried out to reveal the relationships among the chemical species of ABPX01, the color, and the fluorescence emission in various solutions. ABPX01 had various forms: the spirolactone form (ABPX01^0), which is colorless; and the monocationic form (ABPX01H^+) and the dicationic form (ABPX01H_2^<2+>), which are colored. ABPX01H_2^<2+> was identified to be a red fluorescent species. Detailed spectroscopic and electron microscopic investigations led to the assumption that the ABPX01H_2^<2+> formed ion associates with Cl^- as counter anions in HCl aqueous solution, and the nanoand submicrometer-sized colloidal aggregates of ABPX01 hydrochloride exhibit fluorescence emission. Good performance in fluorescent imaging demands large fluorescence quantum yields, and solubility in hydrosoluble media of the markers. We design and synthesize new ABPX derivatives in which the amino groups are incorporated into rigid six-membered rings. The relative fluorescence quantum yields of ABPX101H_2^<2+>, ABPX102H_2^<2+>, and ABPX103H_2^<2+>were drastically increased relative to that of ABPX01H_2^<2+>. All ABPX derivatives commonly exhibited the well-developed bimodal fluorescence emission spectra over a wide range including red and NIR region. The intrinsic solubility of the ABPX dyes is favorable for the photosensitizers of fluorescent imaging and photodynamic therapy.