Tetrapyrrolic macrocycles are suitable for a variety of chemical modifications aimed at new agents for binary antitumor treatment and diagnosis. Previously we have reported that the conjugation of one single carborane cage to the chlorin e₆ macrocycle, a modification designed for tumor sensitization in photodynamic (PDT) and boron neutron capture (BNCT) therapies, yielded the derivative with a higher photosensitizing potency in the models of transplanted rodent tumors. This effect was mechanistically linked to the localization of the carboranylchlorin in membrane organelles due to the carborane moiety. Further exploring the potential of modified tetrapyrrolic compounds as photoradiosensitizers we synthesized the chlorin derivative carrying four closo-carborane cages (44 boron atoms) and 16 fluorine atoms at the periphery of the macrocycle (fluorinated tetracarboranylchlorin, compound 1). For comparison of the properties of 1, its fluorine free congener (tetracarboranylchlorin 6) was obtained. The water soluble 1 and 6 accumulated preferentially in cells selected for resistance to chemotherapeutic drugs (multidrug resistance and cisplatin resistance) than in the parental non-selected counterparts. Compounds 1 and 6 showed a negligible dark cytotoxicity. In contrast, a monochromatic light illumination of cells loaded with low micromolar concentrations of 1 or 6 triggered rapid (within minutes) photonecrosis as determined by the entry of propidium iodide or SYTOX dyes into the parental as well as into resistant cells. In vivo 1 or 6 (up to 80 mg/kgi.p.) caused no general toxicity in Balb/c or C57BL6 mice. Illumination with a monochromatic light of B16 melanoma transplants in mice injected with 5 mg/kg 1 or 6 caused a significant shrinkage of tumor foci, with no re-growth in 77.8 % animals by day 21 post PDT. BNCT on C6 rat glioma xenografts in Balb/c nu/nu mice injected i.p. with 5 mg/kg 1 led to a decrease of tumor foci and cure of animals by day 29 whereas the radiosensitizing potency of 6 was less pronounced. This difference was attributable to a limited intratumoral accumulation of 6. Altogether, an extensive modification of the chlorin macrocycle periphery with polyfluorines and polycarboranes yielded potent and well tolerable compounds for PDT and BNCT.

四吡咯大环化合物适合用于针对二元抗肿瘤治疗和诊断新药的各种化学修饰。以前我们已经报道过，将一个碳硼烷笼与二氢卟酚e ₆大环偶联，这是一种为光动力学（PDT）和硼中子俘获（BNCT）治疗中的肿瘤敏化设计的修饰，在该模型中产生的衍生物具有更高的光敏效力。移植的啮齿动物肿瘤。该作用与由于碳硼烷部分而在膜细胞器中碳硼烷基二氯的定位有关。进一步探索改性四吡咯化合物作为光敏剂的潜力，我们合成了带有四个closo的二氢卟酚衍生物-在大环的外围（氟化四碳烷基二氯，化合物1）-碳硼烷笼（44个硼原子）和16个氟原子。为了比较1的性质，获得了其无氟同类物（四碳硼烷基二氢卟酚6）。相对于未选择的亲本，水溶性1和6优先积聚在针对化学治疗药物的抗性（多药抗性和顺铂抗性）选择的细胞中。化合物1和6显示可忽略的黑暗细胞毒性。相比之下，装有低摩尔浓度1或6的细胞的单色光照明碘化丙锭或SYTOX染料进入亲代细胞和耐药细胞后，触发快速（几分钟内）光坏死。体内1或6（最高80 mg / kgi.p。）在Balb / c或C57BL6小鼠中未引起一般毒性。在注射了5 mg / kg 1或6的小鼠中，用B16黑色素瘤移植物的单色光照射导致肿瘤灶明显缩小，到PDT后第21天，在77.8％的动物中没有再生长。腹腔注射5 mg / kg 1的Balb / c nu / nu小鼠C6大鼠神经胶质瘤异种移植物的BNCT导致肿瘤灶减少和动物治愈至29天，而放射增敏潜能为6不太明显。这种差异归因于有限的肿瘤内累积6。总之，用多氟和多卡巴酮对二氢卟酚大环外围分子进行了广泛修饰，产生了对PDT和BNCT有效且可耐受的化合物。