Synthesis, Characterization and Preliminary Biological Evaluation of P(HPMA)‐b‐P(LLA) Copolymers: A New Type of Functional Biocompatible Block Copolymer

Abstract

We describe a synthetic pathway to functional P(HPMA)-b-P(LLA) block copolymers. The synthesis relies on a combination of ring-opening polymerization of L-lactide, conversion into a chain transfer agent (CTA) for the RAFT polymerization of pentafluorophenyl methacrylate. A series of block copolymers was prepared that exhibited molecular weights $\overline M _{\rm n}$ ranging from 7 600 to 34 300 g · mol(-1) , with moderate PDI between 1.3 and 1.45. These reactive precursor polymers have been transformed into biocompatible P(HPMA)-b-P(LLA) copolymers and their fluorescently labeled derivatives by facile replacement of the pentafluorophenyl groups. The fluorescence label attached to this new type of a partially degradable amphiphilic block copolymer was used to study cellular uptake in human cervix adenocarcinoma (HeLa) cells as well as aggregation behavior by fluorescence correlation spectroscopy (FCS).

P(HPMA)-block-P(LA) copolymers in paclitaxel formulations: Polylactide stereochemistry controls micellization, cellular uptake kinetics, intracellular localization and drug efficiency

“…Yield P(LLA)-CTA: 3.06 g, 91%, 69% functionalization (NMR), Yield P(LLA)-CTA: 2.7 g, 82%, 75% functionalization (NMR). RAFT polymerization of PFMA using the poly(L-lactide) macroinitiator was performed in a Schlenk tube according to our recently published method [38]. The reaction vessel was loaded with 3.5 mg 2,2′-azobis(isobutyronitrile) (AIBN) (0.02 mmol), 0.2 g poly(D-lactide) macroinitiator and 1.58 g of PFMA (12 mmol) (P2R) in 5 mL of dioxane.…”

“…The reaction was carried out according to our recently published method [38]. 1.0 g 4-cyano-4-((thiobenzoyl) sulfanyl)pentanoic acid was dissolved under nitrogen in 100 mL CH 2 Cl 2 .…”

“…In this work we report the synthesis of novel P(HPMA)-block-P(DLLA) copolymers combining ROP, RAFT polymerization as well as the activated ester approach based on our recently published strategy (Scheme 1) [38]. The polymer end group of the poly(lactide) was functionalized with a chain transfer agent enabling the RAFT polymerization [46][47][48] of pentafluorophenyl methacrylate block onto the lactide chain.…”

“…We have recently reported the synthesis of functional P(HPMA)-block-P(LLA) copolymers bearing acidic end groups by a combination of ring opening polymerization (ROP) and reversible addition fragmentation chain transfer (RAFT) polymerization [38]. In addition to its excellent toxicological profile and degradability into naturally occurring metabolites, the physical properties of PLA can be modulated by the degree of crystallization by means of the stereochemistry of the monomer units, i.e., the chain tacticity.…”

Designing nanostructured block copolymer surfaces to control protein adhesion

“…Topdown approaches involve creating patterns through some type of lithography or etching [37], such as soft lithography [38][39][40] or electron beam etching [41,42]. Bottom-up approaches involve self-assembly processes such as liquid crystals [43], supramolecular chemistry [44][45][46], self-assembled monolayers [14,[47][48][49] or block copolymers [25,37,[50][51][52][53][54][55][56][57][58][59][60][61][62][63]. In addition, these systems can be used to understand and model the material-cell or material-protein interactions.…”