Impact of Drug Conjugation Site and Corona Chemistry on the Therapeutic Activity of Polymer Nanorod - Drug Conjugates.
Adv Healthc Mater
; : e2402029, 2024 Sep 05.
Article
in En
| MEDLINE
| ID: mdl-39235719
ABSTRACT
Biocompatible rod-shaped nanoparticles of controlled length can be produced through the heat-induced "living" seeded crystallization-driven self-assembly (CDSA) of poly(2-isopropyl-2-oxazoline)-containing block copolymers. With a hydrophilic poly(2-methyl-2-oxazine) or poly(2-methyl-2-oxazoline) corona, these nanorods have proven non-cytotoxic, non-hemolytic, and ideal for use as a polymer-based drug delivery system. This study demonstrates a facile, one-pot method for the synthesis of mycophenolic acid (MPA)-conjugated block copolymer "unimers" for use in seeded CDSA. Through altering block order during sequential monomer addition cationic ring-opening polymerization (CROP), MPA is conjugated to either the chain end of the core-forming or corona-forming block. This allows bioactive polymer nanorods to be prepared with MPA positioned at either the periphery of the corona, or at the core-corona interface of the nanorod formed during seeded CDSA. In vitro, these nanorods arrest growth in human T and B lymphocytes, with reduced effect in "off-target" monocytes when compared with unconjugated MPA. Furthermore, the conjugation of MPA to the core-corona interface of the nanorods leads to a slower release and reduced cytostatic effect. This study offers a robust investigation into the effect of steric hindrance and corona chemistry on the therapeutic potential of drug-conjugated CDSA nanorods and demonstrates the potential of poly(2-oxazoline)/poly(2-oxazine)-based CDSA nanomaterials as effective drug delivery platforms.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Adv Healthc Mater
Year:
2024
Document type:
Article
Affiliation country:
Australia
Country of publication:
Alemania