Polymers for therapeutic delivery – 2020-010

The design and synthesis of newnanomaterials that enhance or assist the passage of therapeutics acrosscellular membranes both in vitro and in vivo is of immense significance inresearch and therapy. Many drug candidates fail to advance clinically as theydo not have the properties needed to cross biological membranes and reach theirintracellular target. Additionally, poor pharmacokinetics, stability, andoff-target effects leads to undesirable biological responses. Polymericsystems, specifically, cell-penetrating peptides (CPPs) and their syntheticmimics (CPPMs) offer hope for new therapeutic approaches and have played avital role in the advancement of drug delivery technology. The synthesis of moleculartransporters using ring-opening metathesis polymerization (ROMP) is advantageousdue to its living polymerization character. ROMP polymers offer great benefitsover other polymerization techniques such as controlled polymer length, lowpolydispersity index (PDI) and easy of copolymer design. Several groups haveincreased their efforts toward improving the transportation ability ofguanidine-rich molecular transporters. To date, the main modification done toCPPs and their synthetic mimics have included the addition of hydrophobicmoieties to the polymer sequence, however, the guanidine group itself hasmostly been kept “untouched.” Mono and di-alkylation of guanidine has resultedin decreased cellular uptake of CPPs and mimics, leading researchers in otherdirections. FIU inventors have expanded thefield of guanidine-rich molecular transporters into systems with modifiedguanidines. Guanylureas, also referred to as amidinoureas, are moieties withextended hydrogen bonding capacity as compared to guanidine. Utilizingwell-defined polymers, a function-oriented synthesis approach has been employedand the initial results demonstrate improved intracellular protein deliveryusing guanylurea functionalized molecular transporters. Anne Laure Schmitt Olivier aschmitt@fiu.edu 305-348-5948

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