Next Generation Multiresponsive Nanocarriers for Targeted Drug Delivery to Cancer Cells

Abstract

C-H bond activation of 2-methoxyethylamino-bis(phenolate)-yttrium catalysts allowed the synthesis of BAB block copolymers comprised of 2-vinylpyridine (2VP; monomer A) and diethylvinylphosphonate (DEVP; monomer B) as the A and B blocks, respectively, by rare-earth-metal-mediated group-transfer polymerization (REM-GTP). The inherent multi-stimuli-responsive character and drug-loading and -release capabilities were observed to be dependent on the chain length and monomer ratios. Cytotoxicity assays revealed the biocompatibility and nontoxic nature of the obtained micelles toward ovarian cancer (HeLa) cells. The BAB block copolymers effectively encapsulated, transported, and released doxorubicin (DOX) within HeLa cells. REM-GTP enables access to previously unattainable vinylphosphonate copolymer structures, and thereby unlocks their full potential as nanocarriers for stimuli-responsive drug delivery in HeLa cells. The self-evident consequence is the application of these new micelles as potent drug-delivery vehicles with reduced side effects in future cancer therapies.

Metal‐Catalyzed Group‐Transfer Polymerization: A Versatile Tool for Tailor‐Made Functional (Co)Polymers

“…The release of DOX is associated with the decrease of the cancer cell viability. After verification that non‐loaded BAB‐micelles are non‐toxic (Figure , middle), the observed reduced cell viability could be explained by the cytotoxicity of successfully released DOX (Figure , right) …”

“… C−H bond activation of alkynes and heteroaromatics as a versatile tool for mono‐, bi‐ and trifunctional initiators in REM‐GTP …”

“…In addition, the activation of 2,3,5,6‐trimethylpyrazine with (ONOO) t Bu Y(CH 2 TMS)(THF) was of specific interest. The synthesis of B‐A‐X‐A‐B polymers (X=initiator, A=P2VP, B=PDEVP), which are suitable systems for drug delivery, was enabled with this system (vide infra) …”

“…utilized 2‐methoxyethylamino‐bis(phenolate)‐yttrium complexes as highly active catalysts for the generation of AB and ABB′ block copolymers (Figure ) and for the synthesis of B‐A‐X‐A‐B‐systems (X=initiator, A=P2VP, B=PDEVP, B′=PDMVP or PDPVP). For the synthesis of the latter system, a bifunctional tetramethylpyrazine initiator was introduced to the bis(phenolate) yttrium complexes (vide supra) . It was possible to exactly tune the composition of the copolymer through the monomer feed.…”

Studies on the Biocompatibility of Poly(diethyl vinyl‐phosphonate) with a New Fluorescent Marker

“…GTP is a very convenient method by which to prepare end‐group functionalized or block‐copolymerized PDEVPs. A copolymer PDEVP‐block‐poly(2‐vinylpyridine) (P2VP) forms micellar structures, which were considered promising candidates for drug delivery applications and were shown to be nontoxic to ovarian cancer (HeLa) cells . The application of an olefin‐functionalized initiator for GTP of DEVP results in PDEVPs with an olefinic end group, which can be modified by the thiol‐ene click reaction.…”