Well-Defined Diblock Poly(ethylene glycol)-b-Poly(ε-caprolactone)-Based Polymer-Drug Conjugate Micelles for pH-Responsive Delivery of Doxorubicin

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.

ICAM1-Targeting Theranostic Nanoparticles for Magnetic Resonance Imaging and Therapy of Triple-Negative Breast Cancer

“…The loading efficacy of DOX in our study is relatively low compared with other studies. 38 , 39 This may be attributed to the concurrently loading both DOX and Gd within a nanoparticle for the theranostic purpose as well as the synthesis methods. However, the ability of active targeting and extended circulation time of these nanoparticles will lower required drug loading.…”

A pH‐responsive polymer linked with immunomodulatory drugs: synthesis, characteristics and in vitro biocompatibility

“…The aim of this study is to develop pH‐responsive immunotherapeutic drug‐linked micelles. One of the advantages of polymer‐based micelles is that they are relatively easy to synthesize (Ding et al, 2019), and previous studies have used polymer‐based micelles to deliver cancer chemotherapeutic drugs (He et al, 2019; Jafari, Yan, Mohamed, Wu, & Cheng, 2020; Jiang et al, 2014; Tang et al, 2018; W. Wang et al, 2018). Hereby, our results clearly showed that polymers could be used to link cancer immunotherapeutic drugs (Figures 2‐4).…”

Well-Defined pH-Responsive Self-Assembled Block Copolymers for the Effective Codelivery of Doxorubicin and Antisense Oligonucleotide to Breast Cancer Cells

“…According to the particular characteristics of tumor microenvironment (such as low pH and high redox activity) and the aberrant biochemical properties of cancer cells, nanocarriers responsive to endogenous or exogenous stimuli have been designed and developed to enable site-specific control over the release of chemotherapeutics . For instance, we harnessed the pH-sensitivity of imine, acetal, and β-thiopropionate linkages to develop well-defined pH-responsive polylactide-based drug delivery systems with improved anticancer efficacy in our previous works. − However, the effective delivery of a single-component antitumor therapeutic agent may not sufficiently overcome the inherent limitations of chemotherapy, especially drug resistance of tumor cells …”