Antitumor Activity of a Unique Polymer That Incorporates a Fluorescent Self-Assembled Metallacycle

Abstract

Despite the well-known anticancer activity of mono- and multi-nuclear platinum complexes, studies of the antitumor performances of platinum-based supramolecular coordination complexes are rare. Herein, we report on the synthesis of a four-armed amphiphilic copolymer Pt-PAZMB-b-POEGMA containing a theranostic metallacycle M, in which the tetraphenylethene derivative acts as an aggregation-induced emissive fluorescent probe for live cell imaging and the 3,6-bis[trans-Pt(PEt3)2]phenanthrene (PhenPt) is an anticancer drug. This copolymer was further self-assembled into nanoparticles of different sizes and vesicles depending upon the experimental conditions. The impact of the morphology and size of the assemblies on their endocytic pathways, uptake rates, internalization amounts and cytotoxicities were fully investigated. The self-assemblies were further employed to encapsulate doxorubicin (DOX) to achieve a synergistic anticancer effect. Controlled drug release was also realized via amphiphilicity changes and was driven by a glutathione-induced cascade elimination reaction. The DOX-loaded nanoparticles of around 50 nm in size exhibited an excellent antitumor performance as well as a low systemic toxicity, due to an enhanced permeability and retention effect.

Self‐Assembly of Aggregation‐Induced‐Emission Molecules

“…The hierarchical self-assembly of AIE-based macrocyclesc an be ao ne-pot process when amphiphilic polymers are attached to the Lego blocks. Stang et al synthesized af our-armed amphiphilic copolymer, [67] Pt-PAZMB-b-POEGMA, with metallacyle M, in which the TPE derivativea cts as an AIE functional group for live-cell imaging and phenPt is an anticancer drug ( Figure 28). Under differente xperimentalc onditions, this copolymer can self-assemble into nanoparticles or vesicles to encapsulate anticancer drugs.…”

Rhomboidal Pt(II) metallacycle-based NIR-II theranostic nanoprobe for tumor diagnosis and image-guided therapy

“…2C). The NIR-II molecular dye 3 was synthesized from commercially available chemicals, and it was characterized by 1 H NMR, 13 C NMR, and MALDI-TOF-MS (SI Appendix, Figs. S23-S28).…”

“…The macrocyclic structure of SCCs can enhance their cellular uptake compared with their corresponding small molecule precursors as well as the binding with biomolecules with high affinity. Our group and others reported that Pt(II) metallacycles-based SCCs can act as anticancer agents or selective sensors for biologically important analytes as well as interact with DNA and proteins (9)(10)(11)(12)(13)(14). However, the poor photostability, low tumor uptake, and limited penetration depth of Pt-based SCCs are challenges to overcome.…”

Subcellular Duplex DNA and G‐Quadruplex Interaction Profiling of a Hexagonal PtII Metallacycle

“…[12] Their compounds were proposed to accumulate in lysosomes of cancer cells producing low toxicity,yet effectively inducing tumor shrinkage in mouse xenograft models. [13,14] Afurther demonstration of the potential of Pt II -SCCs in biomedicine was provided by Sleiman and Mao,who discovered that Pt II -based metallacycles display fairly good ability to bind DNAG -quadruplexes (G4s) in solution. [13,14] Afurther demonstration of the potential of Pt II -SCCs in biomedicine was provided by Sleiman and Mao,who discovered that Pt II -based metallacycles display fairly good ability to bind DNAG -quadruplexes (G4s) in solution.…”