Department of Electronic Materials and Devices Engineering, Soonchunhyang University, Asan, South Korea.
Department of Chemistry, Pohang University of Science and Technology, Pohang, South Korea.
Drug Deliv. 2022 Dec;29(1):270-283. doi: 10.1080/10717544.2021.2023696.
As mitochondria are potential therapeutic targeting sites for the treatment of human diseases, delivering cytotoxic drugs, antioxidants, and imaging molecules to mitochondria can provide new therapeutic opportunities. In an attempt to develop a new mitochondria-targeting vector, we synthesized sorbitol-based molecular transporters with multiple guanidines, measured their partition coefficients, compared their targeting efficiency using fluorescent images and Pearson's correlation coefficients, and studied cellular uptake mechanisms. To increase the targeting ability of these molecular transporters to mitochondria, alanine-naphthalene as a lipophilic group was attached to the molecular transporter, which improved translocation across cellular membranes and led to higher accumulation in mitochondria. The molecular transporter was able to form an ionic complex with antibiotics, resulting in low cell viability. These data demonstrate that the molecular transporter with a lipophilic group could be utilized as a potential drug delivery vector for treating mitochondrial dysfunction.
由于线粒体是治疗人类疾病的潜在治疗靶点，因此将细胞毒性药物、抗氧化剂和成像分子递送到线粒体可以提供新的治疗机会。为了开发一种新的线粒体靶向载体，我们合成了基于山梨醇的具有多个胍基的分子转运体，测量了它们的分配系数，通过荧光图像和皮尔逊相关系数比较了它们的靶向效率，并研究了细胞摄取机制。为了提高这些分子转运体对线粒体的靶向能力，将疏水性的丙氨酸-萘基连接到分子转运体上，这提高了跨细胞膜的转运能力，并导致在线粒体中的更高积累。该分子转运体能够与抗生素形成离子配合物，从而导致细胞活力降低。这些数据表明，具有疏水性基团的分子转运体可用作治疗线粒体功能障碍的潜在药物递送载体。
