Al-Mansoori Layla, Elsinga Philip, Goda Sayed K
Qatar University, Biomedical Research Centre, Qatar University, Doha 2713, Qatar.
University of Groningen, University Medical Center Groningen (UMCG), Department of Nuclear Medicine and Molecular Imaging, Groningen, the Netherlands.
Biomed Pharmacother. 2021 Dec;144:112260. doi: 10.1016/j.biopha.2021.112260. Epub 2021 Oct 1.
Abnormal structural and molecular changes in malignant tissues were thoroughly investigated and utilized to target tumor cells, hence rescuing normal healthy tissues and lowering the unwanted side effects as non-specific cytotoxicity. Various ligands for cancer cell specific markers have been uncovered and inspected for directional delivery of the anti-cancer drug to the tumor site, in addition to diagnostic applications. Over the past few decades research related to the ligand targeted therapy (LTT) increased tremendously aiming to treat various pathologies, mainly cancers with well exclusive markers. Malignant tumors are known to induce elevated levels of a variety of proteins and peptides known as cancer "markers" as certain antigens (e.g., Prostate specific membrane antigen "PSMA", carcinoembryonic antigen "CEA"), receptors (folate receptor, somatostatin receptor), integrins (Integrin αvβ3) and cluster of differentiation molecules (CD13). The choice of an appropriate marker to be targeted and the design of effective ligand-drug conjugate all has to be carefully selected to generate the required therapeutic effect. Moreover, since some tumors express aberrantly high levels of more than one marker, some approaches investigated targeting cancer cells with more than one ligand (dual or multi targeting). We aim in this review to report an update on the cancer-specific receptors and the vehicles to deliver cytotoxic drugs, including recent advancements on nano delivery systems and their implementation in targeted cancer therapy. We will discuss the advantages and limitations facing this approach and possible solutions to mitigate these obstacles. To achieve the said aim a literature search in electronic data bases (PubMed and others) using keywords "Cancer specific receptors, cancer specific antibody, tumor specific peptide carriers, cancer overexpressed proteins, gold nanotechnology and gold nanoparticles in cancer treatment" was carried out.
对恶性组织中异常的结构和分子变化进行了深入研究,并利用这些变化来靶向肿瘤细胞,从而挽救正常健康组织,并降低非特异性细胞毒性等不良副作用。除了诊断应用外,还发现并研究了各种癌细胞特异性标志物的配体,用于将抗癌药物定向递送至肿瘤部位。在过去几十年中,与配体靶向治疗(LTT)相关的研究大幅增加,旨在治疗各种疾病,主要是具有明确独特标志物的癌症。已知恶性肿瘤会诱导多种蛋白质和肽的水平升高,这些蛋白质和肽被称为癌症“标志物”,如某些抗原(例如前列腺特异性膜抗原“PSMA”、癌胚抗原“CEA”)、受体(叶酸受体、生长抑素受体)、整合素(整合素αvβ3)和分化簇分子(CD13)。选择合适的靶向标志物以及设计有效的配体-药物偶联物都必须经过仔细筛选,以产生所需的治疗效果。此外,由于一些肿瘤会异常高表达不止一种标志物,因此一些研究采用了用不止一种配体靶向癌细胞的方法(双靶向或多靶向)。在本综述中,我们旨在报告癌症特异性受体和递送细胞毒性药物的载体的最新情况,包括纳米递送系统的最新进展及其在靶向癌症治疗中的应用。我们将讨论这种方法面临的优势和局限性以及减轻这些障碍的可能解决方案。为实现上述目标,我们在电子数据库(PubMed等)中使用关键词“癌症特异性受体、癌症特异性抗体、肿瘤特异性肽载体、癌症过表达蛋白、癌症治疗中的金纳米技术和金纳米颗粒”进行了文献检索。