Polyphosphoester conjugates of dinuclear platinum complex: Synthesis and evaluation of cytotoxic and the proapoptotic activity

2020

Molecules

Polymers in which phosphorus is an integral part of the main chain, including polyphosphazenes and polyphosphoesters, have been widely investigated in recent years for their potential in a number of therapeutic applications. Phosphorus, as the central feature of these polymers, endears the chemical functionalization, and in some cases (bio)degradability, to facilitate their use in such therapeutic formulations. Recent advances in the synthetic polymer chemistry have allowed for controlled synthesis methods in order to prepare the complex macromolecular structures required, alongside the control and reproducibility desired for such medical applications. While the main polymer families described herein, polyphosphazenes and polyphosphoesters and their analogues, as well as phosphorus-based dendrimers, have hitherto predominantly been investigated in isolation from one another, this review aims to highlight and bring together some of this research. In doing so, the focus is placed on the essential, and often mutual, design features and structure–property relationships that allow the preparation of such functional materials. The first part of the review details the relevant features of phosphorus-containing polymers in respect to their use in therapeutic applications, while the second part highlights some recent and innovative applications, offering insights into the most state-of-the-art research on phosphorus-based polymers in a therapeutic context.

Section: Water-soluble Polymer-drug Conjugatesmentioning

confidence: 99%

Main-Chain Phosphorus-Containing Polymers for Therapeutic Applications

Strasser

2020

Molecules

“…As demonstrated with the model drug chlorambucil, attachment of the active drug via ester moieties on the hydroxyl end‐groups provides a simple route to prepare covalently bound polymer therapeutics which can release their payload upon endocytosis. Similarly, poly(oxyethylene H‐phosphonate)s can be readily functionalized along the backbone to prepare macromolecular prodrugs . Excellent water solubility, ease of functionalization and degradability make these promising carriers, potentially as alternatives to the ubiquitous but non‐degradable polyethylene glycol‐based systems.…”

Section: Ph‐responsive Polymersmentioning

confidence: 99%

Stimuli‐Responsive Phosphorus‐Based Polymers

2018

Eur J Inorg Chem

This microreview details recent developments in stimuli‐responsive polymers with phosphorus in the main‐chain, in particular polyphosphazenes and polyphosphoesters. The presence of phosphorus in the polymers endows unique properties onto the macromolecules, which can be utilized for the preparation of materials capable of physically responding to specific stimuli. Achieving the desired responsiveness has been much facilitated by recent developments in synthetic polymer chemistry, in particular controlled synthesis and backbone functionalization phosphorus‐based polymers, in order to achieve the required properties and hence responsiveness of the materials. The development of phosphorus‐based polymers which respond to the most important stimuli are discussed, namely, pH, oxidation, reduction, temperature and biological triggers. The polymers are placed in the context not just of each other but also with reference to state‐of‐the‐art organic polymers.

“…Polyphosphoesters are also interesting candidates as polymer therapeutics due to their multivalency and degradability. A range of water soluble linear polyphosphoesters are under investigation, with examples ranging from conjugates of dinuclear platinum complexes to doxorubicin to gene delivery . Furthermore, hyperbranched polyphosphoesters prepared via the self‐condensing ROP procedure have a large number of hydroxyl functional end‐groups for potential loading (Figure ), reminiscent of well‐established, but biopersistent family of macromolecular carriers based on dendritic polyglycerol .…”

Section: Applications In Nanomedicinementioning

confidence: 99%

“…The capability of preparing phosphorus‐based polymers with highly tuned properties, in combination with controlled degradation rates, as described in the previous section, renders these polymers particularly suitable for use in the preparation of advanced biomedical materials . Indeed degradable phosphorus‐based polymers have been widely investigated for their use in medicine including polymer therapeutics, vaccine adjuvants, photodynamic therapy, and tissue engineering . One area where research on phosphorus‐based polymers is particularly focussed is nanomedicine, for which degradable polymers combined with structural control are highly sought.…”

Section: Applications In Nanomedicinementioning

confidence: 99%

Branched Macromolecular Architectures for Degradable, Multifunctional Phosphorus‐Based Polymers

Henke

Brüggemann

Macromol. Rapid Commun.

2017

This feature article briefly highlights some of the recent advances in polymers in which phosphorus is an integral part of the backbone, with a focus on the preparation of functional, highly branched, soluble polymers. A comparison is made between the related families of materials polyphosphazenes, phosphazene/phosphorus-based dendrimers and polyphosphoesters. The work described herein shows this to be a rich and burgeoning field, rapidly catching up with organic chemistry in terms of the macromolecular synthetic control and variety of available macromolecular architectures, whilst offering unique property combinations not available with carbon backbones, such as tunable degradation rates, high multi-valency and facile post-polymerization functionalization. As an example of their use in advanced applications, we highlight some investigations into their use as water-soluble drug carriers, whereby in particular the degradability in combination with multivalent nature has made them useful materials, as underlined by some of the recent studies in this area.