Department of Radiotherapy and Oncology, Goethe University, Frankfurt am Main, Germany.
Expert Opin Drug Discov. 2022 Jul;17(7):733-754. doi: 10.1080/17460441.2022.2077329. Epub 2022 May 23.
Due to its unique functional impact on multiple cancer cell circuits including proliferation, apoptosis, tumor dissemination, DNA damage repair, and immune response, the inhibitor of apoptosis protein (IAP) survivin has gained high interest as a molecular target and a multitude of therapeutics were developed to interfere with survivin expression and functionality. First clinical evaluations of these therapeutics, however, were disappointing highlighting the need to develop advanced delivery systems of survivin-targeting therapeutics.
This review focuses on advancements in nanocarriers to molecularly target survivin in human malignancies. A plethora of nanoparticle platforms, including liposomes, polymeric systems, dendrimers, inorganic nanocarriers, RNA/DNA nanotechnology and exosomes, are discussed in the background of survivin-tailored RNA interference, small molecule inhibitors, dominant negative mutants or survivin vaccination or combined modality treatment with chemotherapeutic drugs and photo-dynamic/photothermal strategies.
Novel therapeutic approaches include the use of biocompatible nanoformulations carrying gene silencing or drug molecules to directly or indirectly target proteins, allow for a more precise and controlled delivery of survivin therapeutics. Moreover, surface modification of these nanocarriers may result in a tumor entity-specific delivery. Therefore, nanomedicine exploiting survivin-tailored strategies in a multimodal background is considered the way forward to enhance the development of future personalized medicine.
凋亡抑制蛋白(IAP)survivin 因其对多种癌细胞回路(包括增殖、凋亡、肿瘤扩散、DNA 损伤修复和免疫反应)具有独特的功能影响,作为分子靶点引起了广泛关注,并且开发了多种治疗方法来干扰 survivin 的表达和功能。然而,这些治疗方法的首次临床评估结果令人失望,这凸显了开发 survivin 靶向治疗的先进递药系统的必要性。
本文重点介绍了用于在人类恶性肿瘤中对 survivin 进行分子靶向的纳米载体的最新进展。本文在 survivin 定制 RNA 干扰、小分子抑制剂、显性负突变体或 survivin 疫苗接种或与化疗药物和光动力/光热策略联合的综合治疗的背景下,讨论了包括脂质体、聚合物系统、树枝状大分子、无机纳米载体、RNA/DNA 纳米技术和外泌体在内的多种纳米颗粒平台。
新型治疗方法包括使用携带基因沉默或药物分子的生物相容性纳米制剂,直接或间接地靶向蛋白质,从而更精确、更受控地递送 survivin 治疗药物。此外,这些纳米载体的表面修饰可能导致肿瘤实体特异性递药。因此,利用 survivin 定制策略进行多模式治疗的纳米医学被认为是提高未来个性化药物开发的途径。