Direct Cytosolic Delivery of Proteins through Coengineering of Proteins and Polymeric Delivery Vehicles
Nanocarrier-mediated protein delivery is a promising strategy for fundamental research and therapeutic applications. However, the efficacy of the current platforms for delivery into cells is limited by endosomal entrapment of delivered protein cargo with concomitantly inefficient access to the cytos...
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| Veröffentlicht in: | Journal of the American Chemical Society 2020-03, Vol.142 (9), p.4349-4355 |
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| container_title | Journal of the American Chemical Society |
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| creator | Lee, Yi-Wei Luther, David C Goswami, Ritabrita Jeon, Taewon Clark, Vincent Elia, James Gopalakrishnan, Sanjana Rotello, Vincent M |
| description | Nanocarrier-mediated protein delivery is a promising strategy for fundamental research and therapeutic applications. However, the efficacy of the current platforms for delivery into cells is limited by endosomal entrapment of delivered protein cargo with concomitantly inefficient access to the cytosol and other organelles, including the nucleus. We report here a robust, versatile polymeric–protein nanocomposite (PPNC) platform capable of efficient (≥90%) delivery of proteins to the cytosol. We synthesized a library of guanidinium-functionalized poly(oxanorborneneimide) (PONI) homopolymers with varying molecular weights to stabilize and deliver engineered proteins featuring terminal oligoglutamate “E-tags”. The polymers were screened for cytosolic delivery efficiency using imaging flow cytometry with cytosolic delivery validated using confocal microscopy and activity of the delivered proteins demonstrated through functional assays. These studies indicate that the PPNC platform provides highly effective and tunable cytosolic delivery over a wide range of formulations, making them robust agents for therapeutic protein delivery. |
| doi_str_mv | 10.1021/jacs.9b12759 |
| format | Article |
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Am. Chem. Soc</addtitle><date>2020-03-04</date><risdate>2020</risdate><volume>142</volume><issue>9</issue><spage>4349</spage><epage>4355</epage><pages>4349-4355</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><abstract>Nanocarrier-mediated protein delivery is a promising strategy for fundamental research and therapeutic applications. However, the efficacy of the current platforms for delivery into cells is limited by endosomal entrapment of delivered protein cargo with concomitantly inefficient access to the cytosol and other organelles, including the nucleus. We report here a robust, versatile polymeric–protein nanocomposite (PPNC) platform capable of efficient (≥90%) delivery of proteins to the cytosol. We synthesized a library of guanidinium-functionalized poly(oxanorborneneimide) (PONI) homopolymers with varying molecular weights to stabilize and deliver engineered proteins featuring terminal oligoglutamate “E-tags”. 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| source | ACS Publications; MEDLINE |
| subjects | Drug Carriers - chemical synthesis Drug Carriers - metabolism Guanidines - chemical synthesis Guanidines - metabolism HEK293 Cells HeLa Cells Humans Imides - chemical synthesis Imides - metabolism Integrases - metabolism Luminescent Proteins - metabolism Nanocomposites - chemistry Polyglutamic Acid - metabolism Polymers - chemical synthesis Polymers - metabolism Protein Engineering Red Fluorescent Protein |
| title | Direct Cytosolic Delivery of Proteins through Coengineering of Proteins and Polymeric Delivery Vehicles |
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