ap1c01131_si_001.pdf (1.5 MB)
Cross-linking Poly(caprolactone)–Polyamidoamine Linear Dendritic Block Copolymers for Theranostic Nanomedicine
journal contribution
posted on 2022-01-06, 20:44 authored by Indika Chandrasiri, Mahesh Loku Yaddehige, Bo Li, Yuzhe Sun, William E. Meador, Austin Dorris, Mohammad Farid Zia, Nathan I. Hammer, Alex Flynt, Jared H. Delcamp, Edward Davis, Alexander Lippert, Davita L. WatkinsThis study represents a comparative
analysis of the solution behavior
and self-assembly pattern of two linear dendritic block copolymers
(LDBCs) composed of a generation 3 polyamidoamine (PAMAM) dendron
as the dendritic block and poly(caprolactone) (PCL) as the linear
block, the latter of which is modified with pendant phenyl groups.
Phenyl substituents were introduced to induce physical cross-linking
in LDBC nanoparticles via π–π stacking. A synthetic
strategy was developed to access phenyl substituted LDBCs through
an ε-caprolactone monomer derivative followed by ring-opening
polymerization to form a library of LDBCs with yields above 83%. Polymersome-like
nanoparticles were observed in water with a 74.4 nm average diameter.
Cross-linked LDBC nanoparticles demonstrated a 37.1% relative decrease
in the critical aggregation concentration (CAC) and a 27.3–41.2%
relative increase of hydrophobic loading efficiency relative to unsubstituted
LDBCs. Nanoparticles loaded with a potential photothermal agent (phenyl
indolizine-C5 (C5)) showed a photothermal efficiency of 49.4% with
a heating temperature of 44.4 °C. These nanoparticles were efficiently
loaded into HEK293 cells with cell viability above 87.5% at the highest
concentration. Upon illumination with red light, nanoparticles loaded
with photothermal agent were able to induce cell death in cancer cells.
This work suggests that the phenyl substituted LDBCs form nanoparticles
with enhanced stability and loading efficiencies compared to conventional
nonphenylated systems and display a greater potential to be used as
nanocarriers in theranostic nanomedicine.
History
Usage metrics
Categories
Keywords
loading efficiencies comparedgeneration 3 polyamidoamineconventional nonphenylated systems3 – 41poly ( caprolactoneinduce cell deathcritical aggregation concentrationpendant phenyl groupsinduce physical crossc5 )) showed4 ° cpotential photothermal agentphotothermal agenthighest concentrationgreater potentialcell viabilityphotothermal efficiencyphenyl substituentsphenyl indolizinework suggestsupon illuminationtheranostic nanomedicinesynthetic strategystudy representssolution behaviorrelative increaserelative decreasered lightopening polymerizationlinking polylinear blockhek293 cellsheating temperatureenhanced stabilityefficiently loadeddendritic blockcomparative analysiscancer cellsassembly pattern83 %.