Combinatorially Designed Lipid-like Nanoparticles for Intracellular Delivery of Cytotoxic Protein for Cancer Therapy

An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein‐based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid‐like materials (termed “lipidoids”), coupled with a rever...

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Published in	Angewandte Chemie International Edition Vol. 53; no. 11; pp. 2893 - 2898
Main Authors	Wang, Ming, Alberti, Kyle, Sun, Shuo, Arellano, Carlos Luis, Xu, Qiaobing
Format	Journal Article
Language	English
Published	Weinheim WILEY-VCH Verlag 10.03.2014 WILEY‐VCH Verlag Wiley Subscription Services, Inc
Edition	International ed. in English
Subjects	Aconitic Acid - analogs & derivatives Aconitic Acid - chemistry Alkanes - chemistry Amines - chemistry Animals Antineoplastic Agents - administration & dosage Cancer cancer therapy Cationic Cell growth Cell Line, Tumor Cell Survival - drug effects Combinatorial analysis Cytotoxicity Humans lipidoids Lipids - chemistry Mathematical models Mice Nanoparticles Nanoparticles - chemistry Neoplasms - drug therapy Platforms protein delivery Proteins Ribonuclease, Pancreatic - metabolism Ribonuclease, Pancreatic - therapeutic use Ribonuclease, Pancreatic - toxicity Ribosome Inactivating Proteins, Type 1 - metabolism Ribosome Inactivating Proteins, Type 1 - therapeutic use Ribosome Inactivating Proteins, Type 1 - toxicity Tumors cancer therapy lipidoids nanoparticles protein delivery
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Abstract	An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein‐based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid‐like materials (termed “lipidoids”), coupled with a reversible chemical protein engineering approach. Using ribonuclease A (RNase A) and saporin as two representative cytotoxic proteins, the combinatorial lipidoids efficiently deliver proteins into cancer cells and inhibit cell proliferation. A study of the structure–function relationship reveals that the electrostatic and hydrophobic interactions between the lipidoids and the protein play a vital role in the formation of protein–lipidoid nanocomplexes and intracellular delivery. A representative lipidoid (EC16‐1) protein nanoparticle formulation inhibits cell proliferation in vitro and suppresses tumor growth in a murine breast cancer model. A protein delivery platform that combines a library of lipid‐like nanoparticles and a reversible chemical protein modification approach is presented. With ribonuclease A (RNase A) and saporin as representative cytotoxic proteins, the nanoparticles deliver proteins into cancer cells and inhibit cell proliferation. A representative lipidoid protein nanoparticle formulation inhibits tumor cell proliferation in vitro and suppresses tumor growth.
AbstractList	An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein-based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid-like materials (termed "lipidoids"), coupled with a reversible chemical protein engineering approach. Using ribonucleaseA (RNaseA) and saporin as two representative cytotoxic proteins, the combinatorial lipidoids efficiently deliver proteins into cancer cells and inhibit cell proliferation. A study of the structure-function relationship reveals that the electrostatic and hydrophobic interactions between the lipidoids and the protein play a vital role in the formation of protein-lipidoid nanocomplexes and intracellular delivery. A representative lipidoid (EC16-1) protein nanoparticle formulation inhibits cell proliferation invitro and suppresses tumor growth in a murine breast cancer model. [PUBLICATION ABSTRACT] An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein-based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid-like materials (termed "lipidoids"), coupled with a reversible chemical protein engineering approach. Using ribonucleaseA (RNaseA) and saporin as two representative cytotoxic proteins, the combinatorial lipidoids efficiently deliver proteins into cancer cells and inhibit cell proliferation. A study of the structure-function relationship reveals that the electrostatic and hydrophobic interactions between the lipidoids and the protein play a vital role in the formation of protein-lipidoid nanocomplexes and intracellular delivery. A representative lipidoid (EC16-1) protein nanoparticle formulation inhibits cell proliferation invitro and suppresses tumor growth in a murine breast cancer model. A protein delivery platform that combines a library of lipid-like nanoparticles and a reversible chemical protein modification approach is presented. With ribonucleaseA (RNaseA) and saporin as representative cytotoxic proteins, the nanoparticles deliver proteins into cancer cells and inhibit cell proliferation. A representative lipidoid protein nanoparticle formulation inhibits tumor cell proliferation invitro and suppresses tumor growth. An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein‐based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid‐like materials (termed “lipidoids”), coupled with a reversible chemical protein engineering approach. Using ribonuclease A (RNase A) and saporin as two representative cytotoxic proteins, the combinatorial lipidoids efficiently deliver proteins into cancer cells and inhibit cell proliferation. A study of the structure–function relationship reveals that the electrostatic and hydrophobic interactions between the lipidoids and the protein play a vital role in the formation of protein–lipidoid nanocomplexes and intracellular delivery. A representative lipidoid (EC16‐1) protein nanoparticle formulation inhibits cell proliferation in vitro and suppresses tumor growth in a murine breast cancer model. An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein‐based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid‐like materials (termed “lipidoids”), coupled with a reversible chemical protein engineering approach. Using ribonuclease A (RNase A) and saporin as two representative cytotoxic proteins, the combinatorial lipidoids efficiently deliver proteins into cancer cells and inhibit cell proliferation. A study of the structure–function relationship reveals that the electrostatic and hydrophobic interactions between the lipidoids and the protein play a vital role in the formation of protein–lipidoid nanocomplexes and intracellular delivery. A representative lipidoid (EC16‐1) protein nanoparticle formulation inhibits cell proliferation in vitro and suppresses tumor growth in a murine breast cancer model. A protein delivery platform that combines a library of lipid‐like nanoparticles and a reversible chemical protein modification approach is presented. With ribonuclease A (RNase A) and saporin as representative cytotoxic proteins, the nanoparticles deliver proteins into cancer cells and inhibit cell proliferation. A representative lipidoid protein nanoparticle formulation inhibits tumor cell proliferation in vitro and suppresses tumor growth. An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein-based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid-like materials (termed "lipidoids"), coupled with a reversible chemical protein engineering approach. Using ribonuclease A (RNase A) and saporin as two representative cytotoxic proteins, the combinatorial lipidoids efficiently deliver proteins into cancer cells and inhibit cell proliferation. A study of the structure-function relationship reveals that the electrostatic and hydrophobic interactions between the lipidoids and the protein play a vital role in the formation of protein-lipidoid nanocomplexes and intracellular delivery. A representative lipidoid (EC16-1) protein nanoparticle formulation inhibits cell proliferation in vitro and suppresses tumor growth in a murine breast cancer model.An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein-based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid-like materials (termed "lipidoids"), coupled with a reversible chemical protein engineering approach. Using ribonuclease A (RNase A) and saporin as two representative cytotoxic proteins, the combinatorial lipidoids efficiently deliver proteins into cancer cells and inhibit cell proliferation. A study of the structure-function relationship reveals that the electrostatic and hydrophobic interactions between the lipidoids and the protein play a vital role in the formation of protein-lipidoid nanocomplexes and intracellular delivery. A representative lipidoid (EC16-1) protein nanoparticle formulation inhibits cell proliferation in vitro and suppresses tumor growth in a murine breast cancer model.
Author	Arellano, Carlos Luis Sun, Shuo Alberti, Kyle Xu, Qiaobing Wang, Ming
Author_xml	– sequence: 1 givenname: Ming surname: Wang fullname: Wang, Ming organization: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA (USA) – sequence: 2 givenname: Kyle surname: Alberti fullname: Alberti, Kyle organization: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA (USA) – sequence: 3 givenname: Shuo surname: Sun fullname: Sun, Shuo organization: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA (USA) – sequence: 4 givenname: Carlos Luis surname: Arellano fullname: Arellano, Carlos Luis organization: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA (USA) – sequence: 5 givenname: Qiaobing surname: Xu fullname: Xu, Qiaobing email: qiaobing.xu@tufts.edu organization: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA (USA)
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/24519972$$D View this record in MEDLINE/PubMed
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Notes	We thank Prof. Gary Sahagian and Dr. Min Fang at Tufts University, School of Medicine for providing 4T1-12B cells and developing the breast cancer mice model. This research was supported by Tufts University. Q.B.X. also acknowledges the Tufts FRAC award and Charlton Award from Tufts University School of Medicine and Pew Scholar for Biomedical Sciences program from Pew Charitable Trusts. K.A. acknowledges the IGERT fellowship from NSF. NSF Pew Charitable Trusts istex:3456438480D3F66E3F86B1C0B46DFE30CA2B19E4 ArticleID:ANIE201311245 Tufts University ark:/67375/WNG-8B382DTJ-2 We thank Prof. Gary Sahagian and Dr. Min Fang at Tufts University, School of Medicine for providing 4T1‐12B cells and developing the breast cancer mice model. This research was supported by Tufts University. Q.B.X. also acknowledges the Tufts FRAC award and Charlton Award from Tufts University School of Medicine and Pew Scholar for Biomedical Sciences program from Pew Charitable Trusts. K.A. acknowledges the IGERT fellowship from NSF. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
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Snippet	An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein‐based therapeutics. A novel... An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein-based therapeutics. A novel...
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SubjectTerms	Aconitic Acid - analogs & derivatives Aconitic Acid - chemistry Alkanes - chemistry Amines - chemistry Animals Antineoplastic Agents - administration & dosage Cancer cancer therapy Cationic Cell growth Cell Line, Tumor Cell Survival - drug effects Combinatorial analysis Cytotoxicity Humans lipidoids Lipids - chemistry Mathematical models Mice Nanoparticles Nanoparticles - chemistry Neoplasms - drug therapy Platforms protein delivery Proteins Ribonuclease, Pancreatic - metabolism Ribonuclease, Pancreatic - therapeutic use Ribonuclease, Pancreatic - toxicity Ribosome Inactivating Proteins, Type 1 - metabolism Ribosome Inactivating Proteins, Type 1 - therapeutic use Ribosome Inactivating Proteins, Type 1 - toxicity Tumors
Title	Combinatorially Designed Lipid-like Nanoparticles for Intracellular Delivery of Cytotoxic Protein for Cancer Therapy
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