Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 15, Issue 21, Pages 25193-25200Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c22146
Keywords
polyurethane; Pt(IV) prodrug-polymer conjugate; nanocapsule; doxorubicin encapsulation; redox-responsive disassembly; dual drug delivery
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This paper presents the synthesis and self-assembly of a polymer-prodrug conjugate, as well as its stimuli-responsive intracellular dual drug delivery. The conjugate forms nanocapsule-like structures in water and releases the active drug in a reducing environment. The encapsulation of a second drug in the conjugate enhances its cell killing efficiency. These findings demonstrate the potential application of such a dual drug delivery approach.
This paper describes the synthesis of a polymer- prodrug conjugate, its aqueous self-assembly, noncovalent encapsulation of a second drug, and stimuli-responsive intracellular dual drug delivery. Condensation polymerization between a functionalized diol and a commercially available diisocyanate in the presence of poly(ethylene glycol) hydroxide (PEG-OH) as the chain stopper produces an ABA-type amphiphilic block copolymer (PU-1) in one pot, with the middle hydrophobic block being a polyurethane containing a pendant tert-butyloxycarbonyl (Boc)protected amine in every repeating unit. Deprotection of the Boc group, followed by covalent attachment of the Pt(IV) prodrug using the pendant amine groups, produces the polymer-prodrug conjugate PU-Pt-1, which aggregates to nanocapsule-like structures in water with a hydrophilic interior. In the presence of sodium ascorbate, the Pt(IV) prodrug can be detached from the polymer backbone, producing the active Pt(II) drug. Cell culture studies show appreciable cell viability by the parent polymer. However, the polymer-prodrug conjugate nanocapsules exhibit cellular uptake and intracellular release of the active drug under a reducing environment. The capsule-like aggregates of the polymer-prodrug conjugate were used for noncovalent encapsulation of a second drug, doxorubicin (Dox), and Dox-loaded PU-Pt-1 aggregate showed a significantly superior cell killing efficiency compared to either of the individual drugs, highlighting the promising application of such a dual-drug-delivery approach.
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