Hydrogen Bond Strength-Mediated Self-Assembly of Supramolecular Nanogels for Selective and Effective Cancer Treatment
Journal
Biomacromolecules
Journal Volume
22
Journal Issue
10
Pages
4446-4457
Date Issued
2021
Author(s)
Abstract
This study provides a significant contribution to the development of multiple hydrogen-bonded supramolecular nanocarrier systems by demonstrating that controlling the hydrogen bond strength within supramolecular polymers represents a crucial factor to tailor the drug delivery performance and enhance the effectiveness of cancer therapy. Herein, we successfully developed two kinds of poly(ethylene glycol)-based telechelic polymers Cy-PEG and UrCy-PEG having self-constituted double and quadruple hydrogen-bonding cytosine (Cy) and ureido-cytosine (UrCy) end-capped groups, respectively, which directly assemble into spherical nanogels with a number of interesting physical characteristics in aqueous solutions. The UrCy-PEG nanogels containing quadruple hydrogen-bonded UrCy dimers exhibited excellent long-term structural stability in a serum-containing biological medium, whereas the double hydrogen-bonded Cy moieties could not maintain the structural integrity of the Cy-PEG nanogels. More importantly, after the drug encapsulation process, a series of in vitro experiments clearly confirmed that drug-loaded UrCy-PEG nanogels induced selective apoptotic cell death in cancer cells without causing significant cytotoxicity to healthy cells, while drug-loaded Cy-PEG nanogels exerted nonselective cytotoxicity toward both cancer and normal cells, indicating that increasing the strength of hydrogen bonds in nanogels plays a key role in enhancing the selective cellular uptake and cytotoxicity of drugs and the subsequent induction of apoptosis in cancer cells. ? 2021 American Chemical Society.
Subjects
Bond strength (materials)
Cell death
Controlled drug delivery
Cytotoxicity
Diseases
Hydrogen bonds
Nanostructured materials
Polyethylenes
Self assembly
Stability
Supramolecular chemistry
Cancer cells
Cancer therapy
Delivery performance
Hydrogen bond strength
Nanocarriers
Nanogels
Physical characteristics
Quadruple hydrogen bonding
Supramolecular polymers
Telechelic polymers
Polyethylene glycols
cytosine
dimer
doxorubicin
hydrogen
macrogol
nanocarrier
nanogel
polymer
drug carrier
apoptosis
aqueous solution
Article
cancer cell
cancer therapy
catalysis
chemical interaction
controlled study
cytotoxicity
drug delivery system
encapsulation
female
flow cytometry
fluorescence intensity
HeLa cell line
human
human cell
hydrodynamics
hydrogen bond
hydrophilicity
hydrophobicity
in vitro study
incubation time
internalization (cell)
matrix assisted laser desorption ionization time of flight mass spectrometry
Michael addition
molecular weight
MTT assay
NIH 3T3 cell line
particle size
pH
quantitative analysis
release assay
scanning electron microscopy
spectrofluorometry
sustained drug release
synthesis
zeta potential
micelle
neoplasm
Drug Carriers
Humans
Hydrogen
Hydrogen Bonding
Micelles
Neoplasms
Polyethylene Glycols
SDGs
Type
journal article