Endogenous substance such as nucleotide as a drug carrier has been proposed as a novel drug delivery system. The nucleotide guanosine-5′-monophosphate (GMP) is used to transport an anticancer drug pemetrexed disodium heptahydrate (PMX) via specific base pairing. The endogenous nature of GMP helps to avoid biocompatibility issues that are generally accompanied with nanocarriers including cytotoxicity, immunogenicity and blood compatibility. Furthermore, the low-molecular weight of the GMP nucleotide carrier significantly boosts the drug loading capacity compared to traditional liposomes and high-molecular weight carriers. Hydrogen-bonding interaction between the carrier and drug realizes the controlled release of loaded drug, and also facilitates large scale manufacture since no additional chemical synthesis is required. More importantly, in vivo experiments reveal that the base-paired GMP:PMX nanovesicles improve the target specificity and pharmacokinetic properties of PMX, and exhibit remarkably enhanced anticancer abilities compared to standalone PMX without any carriers. We envision that this strategy could be extended to other endogenous substances and drugs bearing functional groups capable of specific interaction, and promote the construction of drug delivery systems with inherent biocompatibility, enhanced drug delivery efficacy, and a simplified preparation method.

中文翻译：

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内源核苷酸作为药物载体：碱基对的鸟苷5'-单磷酸酯：培美曲塞囊泡具有增强的抗癌能力

内源性物质例如核苷酸作为药物载体已被提出作为新型药物递送系统。核苷酸鸟苷5'-单磷酸酯（GMP）用于通过特异性碱基配对转运抗癌药物培美曲塞七水合二钠（PMX）。GMP的内源性有助于避免通常与纳米载体伴随的生物相容性问题，包括细胞毒性，免疫原性和血液相容性。此外，与传统脂质体和高分子量载体相比，GMP核苷酸载体的低分子量显着提高了载药量。载体与药物之间的氢键相互作用实现了负载药物的受控释放，并且由于不需要额外的化学合成，因此也有利于大规模生产。更重要的是，体内实验显示，与不含任何载体的独立PMX相比，碱基配对的GMP：PMX纳米囊泡可改善PMX的靶标特异性和药代动力学特性，并具有显着增强的抗癌能力。我们设想该策略可以扩展到其他内源性物质和带有能够特异性相互作用的官能团的药物，并促进具有固有生物相容性，增强的药物递送功效和简化的制备方法的药物递送系统的构建。