Open AccessIntracellular Delivery of Charge-Converted Monoclonal Antibodies by Combinatorial Design of Block/Homo Polyion Complex Micelles
Author(s) -
Ahram Kim,
Yutaka Miura,
Takehiko Ishii,
Ömer Faruk Mutaf,
Nobuhiro Nishiyama,
Horacio Cabral,
Kazunori Kataoka
Publication year - 2016
Publication title -
biomacromolecules
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.689
H-Index - 220
eISSN - 1526-4602
pISSN - 1525-7797
DOI - 10.1021/acs.biomac.5b01335
Subject(s) - micelle , intracellular , biophysics , endosome , chemistry , cytosol , monoclonal antibody , extracellular , antibody , antigen , compartment (ship) , conjugate , biochemistry , biology , enzyme , organic chemistry , immunology , mathematical analysis , oceanography , mathematics , aqueous solution , geology
Direct intracellular delivery of antibodies has gained much attention, although only a few agents have been developed, and none of them has reached clinical stages. The main obstacles here are the insufficient characteristics of delivery systems including stability and appropriate ability for intracellular antibody release. We tailored the structure of polyion complex (PIC) micelles by loading transiently charge-converted antibody derivatives for achieving enhanced stability, delivery to cytosol, and precise antigen recognition inside cells. Citraconic anhydride was used for the charge conversion of the antibody; the optimized degree of modification was identified to balance the stability of PIC micelles in the extracellular compartment and prompt pH-triggered disintegration after their translocation into the acidic endosomal compartment of target cells. The use of a mixture of homo- and block-catiomers in an appropriate ratio to construct PIC micelles substantially enhanced the endosomal escaping efficacy of the loaded antibody, leading to improved recognition of intracellular antigens.