Abstract
Nanoparticles have emerged as versatile carriers for various therapeutics and can potentially treat a wide range of diseases in an accurate and disease-specific manner. Polymeric biomaterials have gained tremendous attention over the past decades, owing to their tunable structure and properties. Aliphatic polyesters have appealing attributes, including biodegradability, non-toxicity, and the ability to incorporate functional groups within the polymer backbone. Such distinctive properties have rendered them as a class of highly promising biomaterials for various biomedical applications. In this article, well-defined alkyne-functionalized poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) diblock copolymer was synthesized and studied for pH-responsive delivery of doxorubicin (DOX). The alkyne-functionalized PEG-b-PCL diblock copolymer was prepared by the synthesis of an alkyne-functionalized ε-caprolactone (CL), followed by ring-opening polymerization (ROP) using PEG as the macroinitiator. The alkyne functionalities of PEG-b-PCL were modified through copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction to graft aldehyde (ALD) groups and obtain PEG-b-PCL-g-ALD. Subsequently, DOX was conjugated on PEG-b-PCL-g-ALD through the Schiff base reaction. The resulting PEG-b-PCL-g-DOX polymer-drug conjugate (PDC) self-assembled into a nano-sized micellar structure with facilitated DOX release in acidic pH due to the pH-responsive linkage. The nanostructures of PDC micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). In vitro studies of the PDC micelles, revealed their improved anticancer efficiency towards MCF-7 cells as compared to free DOX.
Highlights
Cancer is the second cause of death in the United States
PCL was used as the hydrophobic block of polymer-drug conjugate (PDC), which formed drug-conjugated micelles for study, pH-responsive doxorubicin (DOX)
It should be noted that Danafar et al reported previously the studies of PDC micelles with Poly(ethylene glycol) (PEG)-b-PCL diblock copolymer carrying a conjugated doxorubicin moiety at polymer ω-chain-end with a hydrolyzable ester bond [10]
Summary
Cancer is the second cause of death in the United States. The treatment option depends on various factors, including the type and stage of cancer and patient preference. PCL was used as the hydrophobic block of PDC, which formed drug-conjugated micelles for study, pH-responsive doxorubicin (DOX). PCL wasdelivery used asofthe hydrophobic block of PDC, which formed drug-conjugated micelles for pH-responsive delivery of doxorubicin (DOX). It should be noted that Danafar et al reported previously the studies of PDC micelles with PEG-b-PCL diblock copolymer carrying a conjugated doxorubicin moiety at polymer ω-chain-end with a hydrolyzable ester bond [10]. Based on the chemistry innovation of using a functional CL monomer, our current work enables side-chain functionalization of a PEG-b-PCL-based diblock copolymer to conjugate many DOX moieties per macromolecule with acid-labile benzyl imine linkages, leading to a much higher drug loading amount, which is critically important for a drug delivery system
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