Laboratory of Photochemistry, Department of Drug Sciences, University of Catania , Viale Andrea Doria 6, I-95125 Catania, Italy.
Biomacromolecules. 2014 May 12;15(5):1768-76. doi: 10.1021/bm500156z. Epub 2014 Apr 8.
We have developed herein an engineered polymer-based nanoplatform showing the convergence of two-photon fluorescence imaging and bimodal phototherapeutic activity in a single nanostructure. It was achieved through the appropriate choice of three different components: a β-cyclodextrin-based polymer acting as a suitable carrier, a zinc phthalocyanine emitting red fluorescence simultaneously as being a singlet oxygen ((1)O2) photosensitizer, and a tailored nitroaniline derivative, functioning as a nitric oxide (NO) photodonor. The self-assembly of these components results in photoactivable nanoparticles, approximately 35 nm in diameter, coencapsulating a multifunctional cargo, which can be delivered to carcinoma cells. The combination of steady-state and time-resolved spectroscopic and photochemical techniques shows that the two photoresponsive guests do not interfere with each other while being enclosed in their supramolecular container and can thus be operated in parallel under control of light stimuli. Specifically, two-photon fluorescence microscopy allows mapping of the nanoassembly, here applied to epidermal cancer cells. By detecting the red emission from the phthalocyanine fluorophore it was also possible to investigate the tissue distribution after topical delivery onto human skin ex vivo. Irradiation of the nanoassembly with visible light triggers the simultaneous delivery of cytotoxic (1)O2 and NO, resulting in an amplified cell photomortality due to a combinatory effect of the two cytotoxic agents. The potential of dual therapeutic photodynamic action and two-photon fluorescence imaging capability in a single nanostructure make this system an appealing candidate for further studies in biomedical research.
我们开发了一种基于聚合物的纳米平台，该平台具有双光子荧光成像和双模光疗活性，这两种活性在单个纳米结构中得以融合。这是通过适当选择三种不同的成分来实现的：β-环糊精聚合物作为合适的载体，同时发射红光的锌酞菁作为单线态氧（(1)O2）光敏剂，以及定制的硝基苯胺衍生物，作为一氧化氮（NO）光供体。这些成分的自组装形成了光激活纳米颗粒，其直径约为 35nm，共包封了一种多功能货物，可以递送到癌细胞中。稳态和时间分辨光谱和光化学技术的组合表明，两个光响应客体在被封闭在它们的超分子容器中时不会相互干扰，因此可以在光刺激的控制下并行操作。具体来说，双光子荧光显微镜允许对纳米组装体进行映射，这里应用于表皮癌细胞。通过检测酞菁荧光团的红光发射，也可以研究在人体皮肤外植体上局部给药后的组织分布。用可见光照射纳米组装体可引发细胞毒性（1)O2和 NO 的同时释放，由于两种细胞毒性剂的组合效应，导致细胞光致死率增强。在单个纳米结构中实现双治疗光动力作用和双光子荧光成像能力的潜力，使该系统成为生物医学研究中进一步研究的有吸引力的候选者。
