Jung Alain C, Moinard-Butot Fabien, Thibaudeau Chloé, Gasser Gilles, Gaiddon Christian
Laboratory "Streinth", UMR_S 1113 IRFAC, Université de Strasbourg-Inserm, 67200 Strasbourg, France.
Laboratoire de Biologie Tumorale, Institut de Cancérologie Strasbourg Europe, 67200 Strasbourg, France.
Pharmaceutics. 2021 Oct 26;13(11):1788. doi: 10.3390/pharmaceutics13111788.
Metal complexes based on transition metals have rich photochemical and photophysical properties that are derived from a variety of excited state electronic configurations triggered by visible and near-infrared light. These properties can be exploited to produce powerful energy and electron transfer processes that can lead to oxygen-(in)dependent photobiological activity. These principles are the basis of photodynamic therapy (PDT), which is a clinically approved treatment that offers a promising, effective, and noninvasive complementary treatment or even an alternative to treat several types of cancers. PDT is based on a reaction involving a photosensitizer (PS), light, and oxygen, which ultimately generates cytotoxic reactive oxygen species (ROS). However, skin photosensitivity, due to the accumulation of PSs in skin cells, has hampered, among other elements, its clinical development and application. Therefore, these is an increasing interest in the use of (metal-based) PSs that are more specific to tumor cells. This may increase efficacy and corollary decrease side-effects. To this end, metal-containing nanoparticles with photosensitizing properties have recently been developed. In addition, several studies have reported that the use of immunogenic/immunomodulatory metal-based nanoparticles increases the antitumor efficacy of immune-checkpoint inhibitor-based immunotherapy mediated by anti-PD-(L)1 or CTLA-4 antibodies. In this review, we discuss the main metal complexes used as PDT PSs. Lastly, we review the preclinical studies associated with metal-based PDT PSs and immunotherapies. This therapeutic association could stimulate PDT.
基于过渡金属的金属配合物具有丰富的光化学和光物理性质，这些性质源自可见光和近红外光引发的多种激发态电子构型。这些性质可用于产生强大的能量和电子转移过程，从而导致依赖或不依赖氧气的光生物活性。这些原理是光动力疗法（PDT）的基础，光动力疗法是一种临床批准的治疗方法，为治疗多种类型的癌症提供了一种有前景、有效且无创的辅助治疗甚至替代治疗方法。PDT基于一种涉及光敏剂（PS）、光和氧气的反应，最终产生细胞毒性活性氧（ROS）。然而，由于PS在皮肤细胞中的积累导致的皮肤光敏性，在其他因素中，阻碍了其临床开发和应用。因此，人们越来越关注使用对肿瘤细胞更具特异性的（基于金属的）PS。这可能会提高疗效并相应降低副作用。为此，最近开发了具有光敏性质的含金属纳米颗粒。此外，几项研究报告称，使用具有免疫原性/免疫调节性的基于金属的纳米颗粒可提高由抗PD-（L）1或CTLA-4抗体介导的基于免疫检查点抑制剂的免疫疗法的抗肿瘤疗效。在这篇综述中，我们讨论了用作PDT PS的主要金属配合物。最后，我们综述了与基于金属的PDT PS和免疫疗法相关的临床前研究。这种治疗组合可能会促进PDT的发展。
