Fluorescent Polyvinylphosphonate Bioconjugates for Selective Cellular Delivery

Abstract

To date, many poly(ethylene glycol) (PEG) and poly(N-isopropylacrylamide) (PNIPAAm) biomolecule conjugates have been described, but they often show long response times, are not bio-inert, or lose function in biological fluids. Herein, we present a modular synthetic approach to generate polyvinylphosphonate biomolecule conjugates. These conjugates exhibit a sharp phase transition temperature even under physiological conditions where few other examples with this property have been described to date. Furthermore, it was feasible to add biological functions to the polymers via the conjugation step. The polyvinylphosphonate cholesterol constructs are attached to the cellular membrane and the folic acid anchored polymers are shuttled into the cells. This is an exceptional finding through a straightforward synthetic approach.

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

“…In summary, our findings differ from the observations in previous works on PDEVP (bio)‐conjugates . As was shown earlier, PDEVPs tagged with certain bioactive molecules and/or with pyrene chromophores can penetrate cell membranes and exert cytotoxic effects.…”

“…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. Using this approach, PDEVPs with a cholesterol or folic acid anchoring unit were prepared which showed a general level of cytotoxicity that was comparable to the parent PDEVP compound . These polymers, as well as the parent PDEVP, were additionally tagged with pyrene as photoluminescent (PL) marker via transesterification at the phosphonato side group.…”

“…These polymers, as well as the parent PDEVP, were additionally tagged with pyrene as photoluminescent (PL) marker via transesterification at the phosphonato side group. The interaction of the tagged polymers with HMEC‐1 cells was subsequently studied using confocal microscopy, which showed that all of the polymers penetrated into the cells . In addition, all pyrene‐containing polymers were clearly cytotoxic, suggesting that a different PL‐marker needs to be identified for a determination of PDEVP behavior in vivo taking advantage of PL‐imaging techniques.…”

Nicht‐unschuldiger Methylen‐Linker in verbrückten Lewis‐Paar‐ Initiatoren

“…Die Poly(vinylphosphonate), eine Klasse von Polymeren von hçchstem Interesse im biomedizinischen Bereich, [18] wurden als hochmolekulare Produkte mit engen bis extrem engen Dispersitäten erhalten. Die Poly(vinylphosphonate), eine Klasse von Polymeren von hçchstem Interesse im biomedizinischen Bereich, [18] wurden als hochmolekulare Produkte mit engen bis extrem engen Dispersitäten erhalten.…”

“…Zuerst wurde die Molekülstruktur von Me 2 AlCH 2 PMe 2 (1)bei niedriger Te mperatur (100 K) erneut und mit hçherer Auflçsung (0.65 )a ls bei der erstmaligen Aufklärung 1985 bestimmt. [13] In dem aus diesem ersten Experiment abgeleiteten sphärischen Atommodell (independent atom model, IAM) beobachteten wir eine deutliche Vergrçßerung des axialen Al1-C5-Abstandes (2.0091 (13) ) gegenüber dem äquatorialen Al1-C4-Abstand (1.9719-(16) [18] wurden als hochmolekulare Produkte mit engen bis extrem engen Dispersitäten erhalten.…”