Cytotoxicity and Chemosensitizing Activity of Amphiphilic Poly(glycerol)–Poly(alkylene oxide) Block Copolymers

Abstract

All polymeric chemosensitizers proposed thus far have a linear poly(ethylene glycol) (PEG) hydrophilic block. To testify whether precisely this chemical structure and architecture of the hydrophilic block is a prerequisite for chemosensitization, we tested a series of novel block copolymers containing a hyperbranched polyglycerol segment as a hydrophilic block (PPO-NG copolymers) on multi-drug-resistant (MDR) tumor cells in culture. PPO-NG copolymers inhibited MDR of three cell lines, indicating that the linear PEG can be substituted for a hyperbranched polyglycerol block without loss of the polymers' chemosensitizing activity. The extent of MDR reversal increased with the polymers affinity toward the cells and the expression level of P-glycoprotein. In contrast with Pluronic L61, which increases viability of tumor cells in the absence of drugs, PPO-NG chemosensitizers are completely devoid of this property undesired in cancer therapy, making them promising candidates for application as novel MDR reversal agents.

Increase in the length of poly(ethylene oxide) blocks in amphiphilic copolymers facilitates their cellular uptake

“…Similar effects have been observed for polyethoxylated surfactants containing hydrocarbon radicals . Recently, it has been shown that block copolymers of poly(propylene oxide) (PPO) and hyperbranched polyglycerol and those of PDMS and poly(ethylene oxide) (PEO) are also able to suppress MDR tumor cells. Systematic studies performed by Kabanov and coworkers revealed that the potency of Pluronics in inhibiting MDR cells strongly depends on their structure.…”

“…3 H‐labeled copolymers were incubated with MDR human breast adenocarcinoma MCF‐7/ADR cells. This cell line was chosen because it has been routinely used in our group for the analysis of cytotoxicity and chemosensitizing properties of the copolymers studied in this report …”

“…The copolymers assayed in the experiments with liposomes were further tested on living cells. The copolymers were incubated with cells during a fixed time of 1 h. This time was selected because it is routinely used in most studies of copolymer cytotoxicity and their effects on drug efflux pumps …”

Star‐shaped amphiphilic block polyurethane with pentaerythritol core for a hydrophobic drug delivery carrier

“…Amphiphilic copolymers can self‐assemble in aqueous solution to form micelles with hydrophobic segments as the inner core and hydrophilic segments as the outer shell . The hydrophobic core can act as a storage for encapsulating water‐insoluble drugs, which can reduce toxic side effects of entrapped drugs to healthy tissues.…”

Synthesis of fluorescent ABA triblock copolymer via click reaction

“…Linear–dendritic copolymers show some different features when compared to linear block copolymers with the same molecular weight including lower hydrodynamic volumes, high circulation times in the bloodstream, a large number of functional groups on their surfaces and interior voids for the attachment and encapsulation of active moieties, high loading capacities and different in vivo and in vitro cytotoxicity due to their rigid structures . Due to their unique properties, different types of linear–dendritic copolymers have been synthesized for special applications including catalysis, drug carrying and membrane preparation . Recently, the design and synthesis of linear–dendritic copolymers with aliphatic polyether backbone like poly(ethylene glycol) (PEG) have attracted great attention.…”