Thermo/pH dual-responsive micelles based on the host\u2013guest interaction between benzimidazole-terminated graft copolymer and \u03b2-cyclodextrin-functionalized star block copolymer for smart drug delivery

Floria Adeli,Mirzaagha Babazadeh,Farhang Abbasi,Soodabeh Davaran

doi:10.1186/s12951-022-01290-3

Abstract

Novel temperature and pH dual-sensitive amphiphilic micelles were fabricated exploiting the host–guest interaction between benzimidazole-terminated PHEMA-g-(PCL-BM) and β-CD-star-PMAA-b-PNIPAM. The fabricated graft copolymer had a brush-like structure with star side chains. The micelles were utilized as dual-responsive nanocarriers and showed the LCST between 40 and 41 °C. The acidic pH promoted the dissociation of the PHEMA-g-(PCL-BM: β-CD-star-PMAA-b-PNIPAM) micelles. DOX.HCl was loaded into the core of the micelles during self-assembly in an aqueous solution with a high encapsulation efficacy (97.3%). The average size of the amphiphilic micelles was about 80 nm, suitable size for the enhanced permeability and retention effect in tumor vasculature. In an aqueous environment, these micelles exhibited very good self-assembly ability, low CMC value, rapid pH- and thermo-responsiveness, optimal drug loading capacity, and effective release of the drug. The biocompatibility was confirmed by the viability assessment of human breast cancer cell line (MCF-7) through methyl tetrazolium assay. DOX-loaded micelles displayed excellent anti-cancer activity performance in comparison with free DOX.Graphical

Highlights

In the field of drug delivery systems (DDS), nanomaterials are used to transport therapeutic drugs and diagnostic agents to target sites in a controlled manner [1]
The characteristic stretching vibration of PNIPAM at wavelengths of 1560 and 1638 cm−1 remained. These results suggest that the hydrophobic BM moieties inserted into the hydrophobic cavity of β-CD moieties to prepare poly(2-hydroxyethyl methacrylate) (PHEMA)-g-(PCL-BM: β-CD-star-poly(methacrylic acid) (PMAA)-bPNIPAM) micelles via host–guest interaction
Our results showed that micelles formed from PHEMA-g-(PCL-BM: β-CD-star-PMAA-b-PNIPAM) have a pH-responsive behavior due to the presence of benzimidazole units and PMAA units on the graft copolymer chains

Summary

Introduction

In the field of drug delivery systems (DDS), nanomaterials are used to transport therapeutic drugs and diagnostic agents to target sites in a controlled manner [1]. The most popular reversible-deactivation radical polymerization techniques are reversible addition-fragmentation chain transfer polymerization (RAFT) and atom transfer radical polymerization (ATRP) These strategies enable the synthesis of graft copolymer with different compositions and functionality of side chains and make good control over the molecular weight of the synthesized polymers [13, 14]. The choice and combination of these strategies and polymerization techniques make it possible to vary parameters of the resulting graft copolymers, including the size, grafting density, morphology, average degrees of polymerization of the backbone and side chains, and chemical composition. Host–guest chemistry describes complexes that are composed of two or more chemical moieties They are linked together by noncovalent interactions and often show stimuli-responsiveness due to their dynamic properties [20]. The formation and dissociation of the inclusion complexes based on CD with a vast range of guest molecules are closely related to the environmental conditions (temperature and pH), the sizes of the guest and host molecules, as well as, the kinetic and thermodynamic properties of the complexes, which provide the possibilities for the stimuli-responsiveness of the host– guest systems [20]

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