Ruthenium-Containing Block Copolymer Assemblies: Red-Light-Responsive Metallopolymers with Tunable Nanostructures for Enhanced Cellular Uptake and Anticancer Phototherapy.
The use of self-assembled nanostructures consisting of red-light-responsive Ru(II)-containing block copolymers (BCPs) for anticancer phototherapy is demonstrated. Three Ru-containing BCPs with different molecular weights are synthesized. Each BCP contains a hydrophilic poly(ethylene glycol) block and an Ru-containing block. In the Ru-containing block, more than half of the side chains are coordinated with [Ru(2,2':6',2''-terpyridine)(2,2'-biquinoline)](2+) , resulting in more than 40 wt% Ru complex in the BCPs. The Ru complex acts as both a red-light-cleavable moiety and a photoactivated prodrug. Depending on their molecular weights, the BCPs assemble into micelles, vesicles, and large comp…
Engineering von Proteinen an Oberflächen: Von komplementärer Charakterisierung zu Materialoberflächen mit maßgeschneiderten Funktionen
Engineering Proteins at Interfaces: From Complementary Characterization to Material Surfaces with Designed Functions
Abstract Once materials come into contact with a biological fluid containing proteins, proteins are generally—whether desired or not—attracted by the material's surface and adsorb onto it. The aim of this Review is to give an overview of the most commonly used characterization methods employed to gain a better understanding of the adsorption processes on either planar or curved surfaces. We continue to illustrate the benefit of combining different methods to different surface geometries of the material. The thus obtained insight ideally paves the way for engineering functional materials that interact with proteins in a predetermined manner.
Upconversion Nanocarriers Encapsulated with Photoactivatable Ru Complexes for Near-Infrared Light-Regulated Enzyme Activity.
Enzyme activity is important for metabolism, cell functions, and treating diseases. However, remote control of enzyme activity in deep tissue remains a challenge. This study demonstrates near-infrared (NIR) light-regulated enzyme activity in living cells based on upconverting nanoparticles (UCNPs) and a photoactivatable Ru complex. The Ru complex is a caged enzyme inhibitor that can be activated by blue light. To prepare a nanocarrier for NIR photoinhibition of enzyme activity, a UCNP and the caged enzyme inhibitors are encapsulated in a hollow mesoporous silica nanoparticle. In such a nanocarrier, the UCNP can harvest NIR light and convert it into blue light, which can activate the caged e…
Photoactivation of Anticancer Ru Complexes in Deep Tissue: How Deep Can We Go?
Activation of anticancer therapeutics such as ruthenium (Ru) complexes is currently a topic of intense investigation. The success of phototherapy relies on photoactivation of therapeutics after the light passes through skin and tissue. In this paper, the photoactivation of anticancer Ru complexes with 671-nm red light through tissue of different thicknesses was studied. Four photoactivatable Ru complexes with different absorption wavelengths were synthesized. Two of them (Ru3 and Ru4) were responsive to wavelengths in the “therapeutic window” (650–900 nm) and could be activated using 671-nm red light after passing through tissue up to 16-mm-thick. The other two (Ru1 and Ru2) could not be ac…
Ultralow-intensity near-infrared light induces drug delivery by upconverting nanoparticles
Mesoporous silica coated upconverting nanoparticles are loaded with the anticancer drug doxorubicin and grafted with ruthenium complexes as photoactive molecular valves. Drug release was triggered by 974 nm light with 0.35 W cm(-2). Such low light intensity minimized overheating problems and prevented photodamage to biological samples.
Photocleavable core cross-linked polymeric micelles of polypept(o)ides and ruthenium(II) complexes
Core cross-linking of polymeric micelles has been demonstrated to contribute to enhanced stability that can improve the therapeutic efficacy. Photochemistry has the potential to provide spatial resolution and on-demand drug release. In this study, light-sensitive polypyridyl-ruthenium(II) complexes were combined with polypept(o)ides for photocleavable core cross-linked polymeric micelles. Block copolymers of polysarcosine-block-poly(glutamic acid) were synthesized by ring-opening N-carboxyanhydride polymerization and modified with aromatic nitrile-groups on the glutamic acid side chain. The modified copolymers self-assembled into micelles and were cross-linked by cis-diaquabis(2,2'-bipyridi…
Red-Light-Controlled Release of Drug-Ru Complex Conjugates from Metallopolymer Micelles for Phototherapy in Hypoxic Tumor Environments
Traditional photodynamic phototherapy is not efficient for anticancer treatment because solid tumors have a hypoxic microenvironment. The development of photoactivated chemotherapy based on photoresponsive polymers that can be activated by light in the “therapeutic window” would enable new approaches for basic research and allow for anticancer phototherapy in hypoxic conditions. This work synthesizes a novel Ru‐containing block copolymer for photoactivated chemotherapy in hypoxic tumor environment. The polymer has a hydrophilic poly(ethylene glycol) block and a hydrophobic Ru‐containing block, which contains red‐light‐cleavable (650–680 nm) drug–Ru complex conjugates. The block copolymer se…