作为一种代表性的化疗药物，多西紫杉醇（DTX）已被用于乳腺癌治疗数十年。然而，DTX的溶解度较差限制了其疗效，并且基于DTX的治疗增加了治疗过程中C-X-C趋化因子受体4型（CXCR4）表达上调而导致的转移风险。因此，我们在此将CXCR4拮抗剂肽（CTCE）与DTX结合（称为CTCE-DTX）作为一种抗转移剂用于乳腺癌治疗。CTCE-DTX能够自组装成纳米粒子，靶向CXCR4上调的转移性肿瘤细胞，增强DTX的疗效。因此，CTCE-DTX纳米粒子在抑制三阴性乳腺癌的骨特异性转移和肺转移方面取得了有前景的疗效。我们的工作为设计具有协同抗肿瘤疗效的肽-药物共轭物提供了合理的策略。©2023年中国药学会和中国医学科学院药物研究所。Elsevier B.V.生产和托管。

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.