Hydrogen Sulfide Triggered Charge-Reversal Micelles for Cancer-Targeted Drug Delivery and Imaging

Abstract

Currently, the development of polymeric micelles combining diagnosis and targeted therapy is theoretically and practically significant in cancer treatment. In addition, it has been reported that cancer cells can produce large amounts of hydrogen sulfide (H2S) and their survival depends on the content of H2S. In this study, a series of N-(2-hydroxyethyl)-4-azide-1,8-naphthalimide ended amphiphilic diblock copolymer poly(2-hydroxyethyl methacrylate)-block-poly(methyl methacrylate) (N3-Nap-PHEMA-b-PMMA-N3) micelles were prepared. Around cancer tissues, the N3-Nap-PHEMA45-b-PMMA42-N3 micelles exhibited dual characteristics of monitoring H2S and H2S triggered charge reversal with the reduction of the azido group. The surface charge of N3-Nap-PHEMA45-b-PMMA42-N3 micelles reversed from negative to positive after monitoring H2S. With H2S triggered charge reversal, the cellular uptake of DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles was effectively enhanced through electrostatic attraction mediated targeting, and a fast doxorubicin (DOX) release rate was observed. The MTT assay demonstrated that N3-Nap-PHEMA45-b-PMMA42-N3 micelles were biocompatible to HeLa cells, and DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles showed enhanced cytotoxicity in HeLa cells in the presence of H2S. Furthermore, in vivo fluorescence imaging and biodistribution experiments revealed that DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles could provide good tumor imaging and accumulate in tumor tissue. Therefore, N3-Nap-PHEMA45-b-PMMA42-N3 micelles can be used as a promising platform for tumor diagnosis and therapy.

Novel amphiphilic glucose-responsive modified starch micelles for insulin delivery

“…The CMC value of 40% mPEG-DAS-APBA-Cou was lower than that of 40% mPEG-DAS-APBA due to the presence of hydrophobic Cou groups; a lower CMC results in higher micelle stability. 50 The morphologies of the 40% mPEG-DAS-APBA and mPEG-DAS-APBA-Cou polymeric self-assemblies were spherical. The "core-shell" structures of the micelles with different compositions were also very distinct in the TEM observations.…”

Recent progress in H2S activated diagnosis and treatment agents

“…Similarly, Zhang et al 95 used a series of N-(2-hydroxyethyl)-4azide-1,8-naphthalimide-ended amphiphilic diblock copolymer poly(2-hydroxyethyl methacrylate)-block-polymethylmethacrylate (N 3 -Nap-PHEMA-b-PMMA-N 3 ) polymer nano-micelles for loading DOX (Fig. 8C).…”

Photo‐ and pH‐ Dual‐Responsive β‐Cyclodextrin‐Based Supramolecular Prodrug Complex Self‐Assemblies for Programmed Drug Delivery

“…[1][2][3][4][5][6] However,l eakage of the toxic drugs encapsulatedi nt he self-assemblies may occur along with circulation, which can lead to damage to normal tissue. [1][2][3][4][5][6] However,l eakage of the toxic drugs encapsulatedi nt he self-assemblies may occur along with circulation, which can lead to damage to normal tissue.…”

“…Nano self-assemblies, which are efficiently used for the passive targetingo fh ydrophobic drugs by the enhancedp ermeability and retention (EPR) effect, have been demonstrated to be effective in the biomedical field. [1][2][3][4][5][6] However,l eakage of the toxic drugs encapsulatedi nt he self-assemblies may occur along with circulation, which can lead to damage to normal tissue. [7,8] To avoid this phenomenon in the chemical therapy process, much attention has been focused on polymer-drug conjugates to enhance the poor bioavailability of these chemical drugs.…”