Synthesis and In Vitro Cancer Cell Targeting of Folate-Functionalized Biodegradable Amphiphilic Dendrimer-Like Star Polymers

Abstract

By coupling a well-defined PLLA star polymer with six carboxylic acid-terminated polyester dendrons based on 2,2-bis(hydroxymethyl)propionic acid, a biodegradable dendrimer-like star polymer (DLSP) with multiple carboxylic acid groups at the outer surface was successfully synthesized. Conjugation of amine-functionalized folic acids (FA) onto the DLSP yielded a folate-DLSP hybrid as a carrier for targeted drug delivery. The chemical structures were proven by proton nuclear magnetic resonance and size exclusion chromatography. The DLSPs could form unimolecular micelles with a mean particle size of about 18 nm, as determined by dynamic light scattering. Flow cytometry and confocal microscope studies revealed that the cellular uptake of the folate-DLSP hybrid against KB cells (overexpressed folate-receptor) was much higher than that of the neat DLSP (without FA) due to the folate receptor-mediated binding.

Linker chemistry dictates the delivery of a phototoxic organometallic rhenium(i) complex to human cervical cancer cells from core crosslinked star polymer nanoparticles

“…20,23 Multi-armed structured star polymers have been considered as well-defined nanoparticles [24][25][26] that have been widely used for a number of applications, including as nanomedicines, catalysts and emulsification reagents. [27][28][29][30][31][32][33] Our group previously reported the synthesis of narrow dispersity core crosslinked star polymer nanoparticles using a reversible addition fragmentation transfer polymerization (RAFT) arm-first approach, 34,35 in which the arm polymers were chain extended with a suitable cross-linker. We have previously shown that these polymeric nanoparticles demonstrate size tunable pharmacokinetics as well as passive tumor accumulation properties, 32 and cellular association could be manipulated via coronal functionality.…”

Polyester Dendrimers: Smart Carriers for Drug Delivery

“…Wang and coworkers synthesized well-defined folate-functionalized dendrimer-like star polymers, by combining living ring-opening polymerization (ROP) of L-lactide and dendrimer synthesis [207,208]. Here [207,208], a poly(L-lactide) star polymer was selected as the hydrophobic core and non-toxic biodegradable dendrons based on bis-HMPA were used as the shell [208,209]. Surface functionalization using carboxylic acid groups allowed further conjugation with PEG oligomers for water solubility enhancement.…”

“…UV−vis spectroscopy was employed to determine the number of Hilyte488 units incorporated per G1-g3-FA. In vitro results showed that FA-functionalized and anticancer drug-loaded degradable dendrimer-like star polymer (DLSP) could specifically target and kill human KB cells [209].…”

“…Functionalization of dendrimer-like poly(L-lactide) (PLLA) star polymer for drug delivery studies [209].…”

Hydrotropic Polymeric Mixed Micelles Based on Functional Hyperbranched Polyglycerol Copolymers as Hepatoma-Targeting Drug Delivery System

“…Polymeric micelles have attracted widespread interest as carrier systems for poorly water‐soluble drugs for several decades. However, most polymeric micelles can be formed only above the critical micelle concentration 1. Once they are administered in vivo , the extensive dilution may cause the dissociation of the micelles, leading to the rapid release of the drug payload, which will increase the side effects and decrease the bioavailability 2.…”