Self-Assembled Nucleotide/Saccharide-Tethering Polycation-Based Nanoparticle for Targeted Tumor Therapy AITranslate

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DOI：https://doi.org/10.1021/acsmaterialslett.0c00089

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Development of novel concepts to construct drug vehicles for efficient encapsulation of hydrophobic drugs and targeted therapy is highly desirable to biomedical science. It remains a challenge to create effective noncovalent linkage between the components within the drug vectors. In this work, we report a supramolecular approach to construct multifunctional nanoparticles, which combined tumor-targeting capability via saccharide, cell penetration via positive-charged surface, and chemotherapeutic function via drug delivery for cancer therapy. A endogenous self-associating nucleotide (guanosine monophosphate) noncovalently bonded with a hydrophobic nucleoside analogue drug (clofarabine) to form nanofibrils, which were transformed to spherical nanoparticles by assembling with a fructose/ethanolamine-functionalized starlike poly(glycidyl methacrylate)-based cationic polymer. Noncovalent cavities within the nanoparticles were created, through the nucleotide self-association, and acted as linkage between the hydrophilic cationic polymer and the drug. The saccharide-tethering polycation and nucleotide components were labeled with fluorescent dyes, respectively, to image the endocytosis and biodistribution. In vitro and in vivo results show that the functional nanoparticles exhibited good capabilities of the targeted accumulation of the nanoparticles and delivery of drugs in cancer cells and tumor sites, leading to a robust anticancer effect.