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pH/Sugar Dual Responsive Core-Cross-Linked PIC Micelles for Enhanced Intracellular Protein Delivery
- Source :
- Biomacromolecules. 14:3434-3443
- Publication Year :
- 2013
- Publisher :
- American Chemical Society (ACS), 2013.
-
Abstract
- Herein, a series of biocompatible, robust, pH/sugar-sensitive, core-cross-linked, polyion complex (PIC) micelles based on phenylboronic acid-catechol interaction were developed for protein intracellular delivery. The rationally designed poly(ethylene glycol)-b-poly(glutamic acid-co-glutamicamidophenylboronic acid) (PEG-b-P(Glu-co-GluPBA)) and poly(ethylene glycol)-b-poly(l-lysine-co-ε-3,4-dihydroxyphenylcarboxyl-L-lysine) (PEG-b-P(Lys-co-LysCA)) copolymers were successfully synthesized and self-assembled under neutral aqueous condition to form uniform micelles. These micelles possessed a distinct core-cross-linked core-shell structure comprised of the PEG outer shell and the PGlu/PLys polyion complex core bearing boronate ester cross-linking bonds. The cross-linked micelles displayed superior physiological stabilities compared with their non-cross-linked counterparts while swelling and disassembling in the presence of excess fructose or at endosomal pH. Notably, either negatively or positively charged proteins can be encapsulated into the micelles efficiently under mild conditions. The in vitro release studies showed that the release of protein cargoes under physiological conditions was minimized, while a burst release occurred in response to excess fructose or endosomal pH. The cytotoxicity of micelles was determined by cck-8 assay in HepG2 cells. The cytochrome C loaded micelles could efficiently delivery proteins into HepG2 cells and exhibited enhanced apoptosis ability. Hence, this type of core-cross-linked PIC micelles has opened a new avenue to intracellular protein delivery.
- Subjects :
- Polymers and Plastics
Cell Survival
Polymers
Catechols
Antineoplastic Agents
Apoptosis
Bioengineering
Fructose
Micelle
Biomaterials
Structure-Activity Relationship
chemistry.chemical_compound
Polymer chemistry
PEG ratio
Materials Chemistry
Copolymer
Humans
Organic chemistry
Molecule
Micelles
Ions
chemistry.chemical_classification
Aqueous solution
Dose-Response Relationship, Drug
Molecular Structure
Chemistry
Cytochromes c
Hep G2 Cells
Polymer
Hydrogen-Ion Concentration
Boronic Acids
Cross-Linking Reagents
Drug Screening Assays, Antitumor
Ethylene glycol
Subjects
Details
- ISSN :
- 15264602 and 15257797
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Biomacromolecules
- Accession number :
- edsair.doi.dedup.....5a630c0bdb06f219df69b90bb80526ab