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

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.