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1.
Angew Chem Int Ed Engl ; 63(14): e202316323, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38317057

RESUMO

We synthesize supramolecular poly(disulfide) (CPS) containing covalently attached cucurbit[7]uril (CB[7]), which is exploited not only as a carrier to deliver plasmid DNA encoding destabilized Cas9 (dsCas9), but also as a host to include trimethoprim (TMP) by CB[7] moieties through the supramolecular complexation to form TMP@CPS/dsCas9. Once the plasmid is transfected into tumor cells by CPS, the presence of polyamines can competitively trigger the decomplexation of TMP@CPS, thereby displacing and releasing TMP from CB[7] to stabilize dsCas9 that can target and edit the genomic locus of PLK1 to inhibit the growth of tumor cells. Following the systemic administration of TMP@CPS/dsCas9 decorated with hyaluronic acid (HA), tumor-specific editing of PLK1 is detected due to the elevated polyamines in tumor microenvironment, greatly minimizing off-target editing in healthy tissues and non-targeted organs. As the metabolism of polyamines is dysregulated in a wide range of disorders, this study offers a supramolecular approach to precisely control CRISPR/Cas9 functions under particular pathological contexts.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Sistemas CRISPR-Cas/genética , Plasmídeos , DNA , Poliaminas
2.
RSC Adv ; 11(62): 39508-39517, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-35492488

RESUMO

Based on density functional theory, the adsorption behavior of 5-fluorouracil (5-Fu) on B40 and its derivatives has been explored. It was observed that 5-Fu prefers to combine with the corner boron atom of the B40 cage via one of its oxygen atoms, forming a strong polar covalent B-O bond. The adsorption energy of 5-Fu on B40 was calculated to be -11.15 kcal mol-1, and thus, it can be duly released from B40 by protonation in the slightly acidic environment of tumor tissue, which makes for reducing the toxic and side effects of this drug. Additionally, the substituent and embedding effect of Mg, Al, Si, Mn, Cu, and Zn atoms on the drug delivery performance of B40 have been also considered. We hope this work could offer some implications for the potential application of boron-based nanomaterials, such as B40 in drug delivery.

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