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Endogenous nucleotide as drug carrier: base-paired guanosine-5′-monophosphate:pemetrexed vesicles with enhanced anticancer capability

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Abstract

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.

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Acknowledgements

This work was supported by the Shanghai Municipal Government (18JC1410800) and the National Natural Science Foundation of China (51690151, 21774077). We would like to thank Prof. Yongfeng Zhou for helpful discussion on the structure of nanoparticles, Jieli Wu and Bona Dai for the help on NMRs, Jiaojian Yuan for the help on LC-MS, and Jiwen Qian for the help on animal experiments. We would also like to thank Shenzhen Neptunus Pharmaceutical Research Institute Co., Ltd. for generous donation of pemetrexed disodium heptahydrate and useful information on cell screening.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, China

    Lei Xu, Chunyang Yu, Dali Wang, Ji Pang, Leilei Shi, Yue Su, Deyue Yan & Xinyuan Zhu

  2. School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, 116029, China

    Lidong Gong

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  1. Lei Xu
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  2. Chunyang Yu
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Correspondence to Dali Wang or Xinyuan Zhu.

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Endogenous nucleotide as drug carrier: base-paired guanosine-5’-monophosphate:pemetrexed vesicles with enhanced anticancer capability

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Xu, L., Yu, C., Wang, D. et al. Endogenous nucleotide as drug carrier: base-paired guanosine-5′-monophosphate:pemetrexed vesicles with enhanced anticancer capability. Sci. China Chem. 63, 244–253 (2020). https://doi.org/10.1007/s11426-019-9614-2

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