Gao Bingjie, Schäfers Charlotte, Kuan Seah Ling, Weil Tanja
Department of Synthesis of Macromolecules, Max Planck Institute for Polymer Research, 55128, Mainz, Germany.
Johannes Gutenberg University, Duesbergweg 10-14, 55128, Mainz, Germany.
Macromol Biosci. 2025 Jun;25(6):e2400610. doi: 10.1002/mabi.202400610. Epub 2025 Mar 25.
The potential of photodynamic therapy (PDT) in combination with chemotherapy to improve treatment outcomes for triple-negative breast cancer (TNBC), for which no targeted therapy is available, is the subject of considerable investigation. In PDT, photosensitizers (PSs) are frequently administered directly but do not selectively target cancer cells. To address the delivery of a PS to TNBC and enhance cellular uptake, the Ru-NH-modified avidin bioconjugate (Avi) via Tyr-specific modification using the Mannich reaction is prepared. The Avi is further assembled with the cinnamoyl peptide-F(D)LF(D)LFK-NH (FK), which binds to formyl peptide receptor 1, overexpressed in TNBC. Notably, the modified Avi still possesses the ability to efficiently bind biotin for the assembly of up to four copies of the FK peptides. The resultant FK-Avi exhibited an IC value of 0.36 ± 0.08 µM, which is ≈3.5-fold lower than that of Avi (1.25 ± 0.09 µM), upon irradiation in the triple-negative MDA-MB-231 breast cancer cells. FK-Avi also shows efficient uptake in MDA-MB-231 tumor spheroids and exhibited significant toxicity after irradiation compared to the control Avi. The presented strategy has the potential to improve the efficacy of targeted PDT to meet the high demand for targeted therapies to treat TNBC, such as targeted adjuvant treatment after breast cancer surgery.
光动力疗法（PDT）联合化疗改善三阴性乳腺癌（TNBC）治疗效果的潜力是大量研究的主题，因为三阴性乳腺癌没有可用的靶向治疗方法。在光动力疗法中，光敏剂（PSs）通常直接给药，但不会选择性地靶向癌细胞。为了解决将光敏剂递送至三阴性乳腺癌并增强细胞摄取的问题，通过曼尼希反应利用酪氨酸特异性修饰制备了钌-氨基修饰的抗生物素蛋白生物共轭物（Avi）。Avi进一步与肉桂酰肽-F(D)LF(D)LFK-NH（FK）组装，该肽与在三阴性乳腺癌中过表达的甲酰肽受体1结合。值得注意的是，修饰后的Avi仍然具有有效结合生物素的能力，可用于组装多达四个拷贝的FK肽。在三阴性MDA-MB-231乳腺癌细胞中照射后，所得的FK-Avi的IC值为0.36±0.08µM，比Avi（1.25±0.09µM）低约3.5倍。FK-Avi在MDA-MB-231肿瘤球体中也显示出有效摄取，并且与对照Avi相比，照射后表现出显著的毒性。所提出的策略有可能提高靶向光动力疗法的疗效，以满足治疗三阴性乳腺癌对靶向治疗的高需求，例如乳腺癌手术后的靶向辅助治疗。
