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Polymeric Micelles Loading Proteins through Concurrent Ion Complexation and pH‐Cleavable Covalent Bonding for In Vivo Delivery
Author(s) -
Tao Anqi,
Huang George Lo,
Igarashi Kazunori,
Hong Taehun,
Liao Suiyang,
Stellacci Francesco,
Matsumoto Yu,
Yamasoba Tatsuya,
Kataoka Kazunori,
Cabral Horacio
Publication year - 2020
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201900161
Subject(s) - micelle , chemistry , nanocarriers , myoglobin , ethylene glycol , covalent bond , biophysics , moiety , isoelectric point , drug delivery , combinatorial chemistry , biochemistry , organic chemistry , aqueous solution , biology , enzyme
Protein drugs have great potential as targeted therapies, yet their application suffers from several drawbacks, such as instability, short half‐life, and adverse immune responses. Thus, protein delivery approaches based on stimuli‐responsive nanocarriers can provide effective strategies for selectively enhancing the availability and activation of proteins in targeted tissues. Herein, polymeric micelles with the ability of encapsulating proteins are developed via concurrent ion complexation and pH‐cleavable covalent bonding between proteins and block copolymers directed to pH‐triggered release of the protein payload. Carboxydimethylmaleic anhydride (CDM) is selected as the pH‐sensitive moiety, since the CDMamide bond is stable at physiological pH (pH 7.4), while it cleaves at pH 6.5, that is, the pathophysiological pH of tumors and inflammatory tissues. By using poly(ethylene glycol)‐poly( l ‐lysine) block copolymers having 45% CDM addition, different proteins with various sizes and isoelectric points are loaded successfully. By using myoglobin‐loaded micelles (myo/m) as a model, the stability of the micelles in physiological conditions and the dissociation and release of functional myoglobin at pH 6.5 are successfully confirmed. Moreover, myo/m shows extended half‐life in blood compared to free myoglobin and micelles assembled solely by polyion complex, indicating the potential of this system for in vivo delivery of proteins.