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J Am Chem Soc ; 143(3): 1296-1300, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33433203


Oligonucleotide-based materials such as spherical nucleic acid (SNA) have been reported to exhibit improved penetration through the epidermis and the dermis of the skin upon topical application. Herein, we report a self-assembled, skin-depigmenting SNA structure, which is based upon a bifunctional oligonucleotide amphiphile containing an antisense oligonucleotide and a tyrosinase inhibitor prodrug. The two components work synergistically to increase oligonucleotide cellular uptake, enhance drug solubility, and promote skin penetration. The particles were shown to reduce melanin content in B16F10 melanoma cells and exhibited a potent antimelanogenic effect in an ultraviolet B-induced hyperpigmentation mouse model.

ACS Appl Mater Interfaces ; 12(41): 45830-45837, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32936615


Herein, we report a novel strategy to enhance the antisense activity and the pharmacokinetics of therapeutic oligonucleotides. Through the DNA hybridization chain reaction, DNA hairpins modified with poly(ethylene glycol) (PEG) form a bottlebrush architecture consisting of a double-stranded DNA backbone, PEG side chains, and antisense overhangs. The assembled structure exhibits high PEG density on the surface, which suppresses unwanted interactions between the DNA and proteins (e.g., enzymatic degradation) while allowing the antisense overhangs to hybridize with the mRNA target and thereby deplete target protein expression. We show that these PEGylated bottlebrushes targeting oncogenic KRAS can achieve much higher antisense efficacy compared with unassembled hairpins with or without PEGylation and can inhibit the proliferation of lung cancer cells bearing the G12C mutant KRAS gene. Meanwhile, these structures exhibit elevated blood retention times in vivo due to the biological stealth properties of PEG and the high molecular weight of the overall assembly. Collectively, this self-assembly approach bears the characteristics of a simple, safe, yet highly translatable strategy to improve the biopharmaceutical properties of therapeutic oligonucleotides.

ACS Nano ; 12(8): 8323-8329, 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30027730


Sodium-ion batteries offer an attractive option for grid-level energy storage due to the high natural abundance of sodium and low material cost of sodium compounds. Phosphorus (P) is a promising anode material for sodium-ion batteries, with a theoretical capacity of 2596 mAh/g. The red phosphorus (RP) form has worse electronic conductivity and lower initial Coulombic efficiency than black phosphorus (BP), but high material cost and limited production capacity have slowed the development of BP anodes. To address these challenges, we have developed a simple and scalable method to synthesize layered BP/graphene composite (BP/rGO) by pressurization at room temperature. A carbon-black-free and binder-free BP/rGO anode prepared with this method achieved specific charge capacities of 1460.1, 1401.2, 1377.6, 1339.7, 1277.8, 1123.78, and 720.8 mAh/g in a rate capability test at charge and discharge current densities of 0.1, 0.5, 1, 5, 10, 20, and 40 A/g, respectively. In a cycling performance test, after 500 deep cycles, the capacity of BP/rGO anodes stabilized at 1250 and 640 mAh/g at 1 and 40 A/g, respectively, which marks a significant performance improvement for sodium-ion battery anodes.