Clyde Overby, Baixue Xiao, Tiana Salomon, Jorge Jimenez, Nathaniel Silvia, Danielle S. W. Benoit
{"title":"合理设计的齐聚物肽可改善阳离子二嵌段共聚物纳米颗粒给药系统的 siRNA 给药效果","authors":"Clyde Overby, Baixue Xiao, Tiana Salomon, Jorge Jimenez, Nathaniel Silvia, Danielle S. W. Benoit","doi":"10.1021/acsanm.4c01995","DOIUrl":null,"url":null,"abstract":"Nanoparticle drug-delivery systems (NP DDS) have proven to be tremendously impactful for delivering therapeutic agents in cancer treatments, vaccinations, gene therapy, and diagnostics, and enabled agents such as RNA therapeutics. However, the exposure of NP DDS to biological milieus leads to the rapid adsorption of proteins and other molecules, forming a proteinaceous corona that obscures NP surface characteristics and controls the biological interactions of the NP DDS. Surface modifications, including poly(ethylene glycol) (PEG) and synthetic zwitterionic polymers, reduce protein adsorption yet lack monomer-scale tunability, have off-target immunological effects, and suffer from targeting-limited steric hindrance, altogether motivating the development of alternative approaches. Peptides can uniquely form many zwitterions and have shown promise in reducing and controlling the NP protein corona as a function of the peptide sequence. However, the impact of zwitterionic peptides (ZIPs) on the drug-delivery properties of polymeric NPs has not been explored. In this work, diverse ZIPs computationally predicted to reduce protein adsorption by assessing peptide–peptide β-strand interaction energies were conjugated to pH-responsive cationic NPs. The resulting ZIP-NP conjugates exhibited up to 88% reduced protein adsorption and a range of siRNA-mediated gene knockdown that correlates with interaction energies. These data suggest that the peptide–peptide interaction energy is a promising design parameter for ZIPs for further model development. ZIP-NP also exhibited sequence-dependent variations in cellular uptake and circulation half-life, indicating that ZIP-NPs are suitable for tuning and improving NP drug-delivery characteristics.","PeriodicalId":6,"journal":{"name":"ACS Applied Nano Materials","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rationally Designed Zwitterionic Peptides Improve siRNA Delivery of Cationic Diblock Copolymer-Based Nanoparticle Drug-Delivery Systems\",\"authors\":\"Clyde Overby, Baixue Xiao, Tiana Salomon, Jorge Jimenez, Nathaniel Silvia, Danielle S. W. 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Rationally Designed Zwitterionic Peptides Improve siRNA Delivery of Cationic Diblock Copolymer-Based Nanoparticle Drug-Delivery Systems
Nanoparticle drug-delivery systems (NP DDS) have proven to be tremendously impactful for delivering therapeutic agents in cancer treatments, vaccinations, gene therapy, and diagnostics, and enabled agents such as RNA therapeutics. However, the exposure of NP DDS to biological milieus leads to the rapid adsorption of proteins and other molecules, forming a proteinaceous corona that obscures NP surface characteristics and controls the biological interactions of the NP DDS. Surface modifications, including poly(ethylene glycol) (PEG) and synthetic zwitterionic polymers, reduce protein adsorption yet lack monomer-scale tunability, have off-target immunological effects, and suffer from targeting-limited steric hindrance, altogether motivating the development of alternative approaches. Peptides can uniquely form many zwitterions and have shown promise in reducing and controlling the NP protein corona as a function of the peptide sequence. However, the impact of zwitterionic peptides (ZIPs) on the drug-delivery properties of polymeric NPs has not been explored. In this work, diverse ZIPs computationally predicted to reduce protein adsorption by assessing peptide–peptide β-strand interaction energies were conjugated to pH-responsive cationic NPs. The resulting ZIP-NP conjugates exhibited up to 88% reduced protein adsorption and a range of siRNA-mediated gene knockdown that correlates with interaction energies. These data suggest that the peptide–peptide interaction energy is a promising design parameter for ZIPs for further model development. ZIP-NP also exhibited sequence-dependent variations in cellular uptake and circulation half-life, indicating that ZIP-NPs are suitable for tuning and improving NP drug-delivery characteristics.
期刊介绍:
ACS Applied Nano Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics and biology relevant to applications of nanomaterials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important applications of nanomaterials.