Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Mueang, Chiang Mai, Thailand.
Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Kasetsart University, Bangkok, Thailand.
Bioorg Chem. 2021 Feb;107:104601. doi: 10.1016/j.bioorg.2020.104601. Epub 2021 Jan 1.
Acute lymphoblastic leukemia (ALL) or white blood cell cancer is one of the major causes that kills many children worldwide. Although various therapeutic agents are available for ALL treatment, the new drug discovery and drug delivery system are needed to improve their effectiveness, to reduce the toxicity and side-effect, and to enhance their selectivity to target cancer cells. CXCR4 is a protein expressed on the surface of various types of cancer cell including ALL. In this work, the CXCR4-targeted PAMAM dendrimer was constructed by conjugating G5 PAMAM with a CXCR4 antagonist, LFC131. The results revealed that the LFC131-conjugated G5 PAMAM selectively targeted CXCR4 expressing leukemic precursor B cells (NALM-6) and the migration of NALM-6 cells induced by SDF-1α was inhibited at non-cytotoxic concentration. Further research based on this findings may contribute to potential anti-metastatic drugs for lymphoblastic leukemia.
急性淋巴细胞白血病 (ALL) 或白细胞癌是全球许多儿童死亡的主要原因之一。尽管有各种治疗药物可用于 ALL 治疗，但仍需要新的药物发现和药物输送系统来提高其疗效，降低毒性和副作用，并增强其对癌细胞的选择性。趋化因子受体 4 (CXCR4) 是一种在包括 ALL 在内的各种类型癌细胞表面表达的蛋白质。在这项工作中，通过将 G5 PAMAM 与 CXCR4 拮抗剂 LFC131 缀合，构建了靶向 CXCR4 的 PAMAM 树枝状大分子。结果表明，LFC131 缀合的 G5 PAMAM 选择性地靶向表达 CXCR4 的白血病前体 B 细胞 (NALM-6)，并在非细胞毒性浓度下抑制 SDF-1α 诱导的 NALM-6 细胞迁移。基于这些发现的进一步研究可能有助于开发潜在的抗白血病转移药物。
