“Light Switch” Effect Upon Binding of Ru-dppz to Water-Soluble Conjugated Polyelectrolyte Dendrimers

We report the “light switch” effect of [Ru­(bpy)­₂­(dppz)]­²⁺ (where bpy = 2,2′-bipyridine and dppz = dipyrido­[3,2-a:2′,3′-c] phenazine, Ru-dppz) in the presence of anionic conjugated polyelectrolyte dendrimers (CPDs). The metal-to-ligand charge-transfer luminescence from Ru-dppz is efficient in the presence of CPD because the complex is shielded from water by binding to the hydrophobic dendrimer core

Protein Nanocages for Delivery and Release of Luminescent Ruthenium(II) Polypyridyl Complexes

In this report, noncovalent encapsulation of hydrophobic ruthenium­(II) polyridyl complexes, Ru­(bpy)₂dppz²⁺ and Ru­(phen)₂dppz²⁺, into apoferritin cavity was achieved with high loading contents by effective prevention of Ru complex-induced protein aggregation, without disruption of protein native architecture. The Ru-loaded luminescent nanocomposites have demonstrated improved water solubility, easy manipulation, reduced cytotoxicity, and enhanced cellular uptake as compared to the nontreated Ru complexes

Protein Nanocages for Delivery and Release of Luminescent Ruthenium(II) Polypyridyl Complexes

In this report, noncovalent encapsulation of hydrophobic ruthenium­(II) polyridyl complexes, Ru­(bpy)₂dppz²⁺ and Ru­(phen)₂dppz²⁺, into apoferritin cavity was achieved with high loading contents by effective prevention of Ru complex-induced protein aggregation, without disruption of protein native architecture. The Ru-loaded luminescent nanocomposites have demonstrated improved water solubility, easy manipulation, reduced cytotoxicity, and enhanced cellular uptake as compared to the nontreated Ru complexes

Tunable Thioesters as “Reduction” Responsive Functionality for Traceless Reversible Protein PEGylation

Disulfide has been the only widely used functionality to serve as a reduction responsive trigger in drug delivery. We introduce thioester as a novel thiol responsive chemistry for drug delivery, whose reactivity can be conveniently modulated by choosing the appropriate steric environment around the thioester. Compared with disulfides, thioesters are facile to synthesize and have an order of magnitude broader kinetic tunability. A novel traceless reversible protein PEGylation reagent is developed based on thioester chemistry

Remarkable Photophysics and Amplified Quenching of Conjugated Polyelectrolyte Oligomers

We report the photophysics and fluorescence quenching of a series of monodisperse, anionic π-conjugated oligomers that are molecularly dissolved in aqueous solution. These structurally well-defined oligomers feature oligo­(phenylene ethynylene) backbones with two −CH₂COO^– units on each repeat unit, with overall lengths of 5, 7, and 9 repeats. The ionic oligomers display a structured fluorescence band with high quantum efficiency in water, in contrast to the low fluorescence quantum efficiency and pronounced aggregation displayed by structurally similar oligomeric and polymeric (phenylene ethynylene) conjugated polyelectrolytes studied previously. Stern–Volmer (SV) fluorescence quenching studies using cationic charge- and energy-transfer quenchers reveal that all of the oligomers give rise to SV quenching constants (<i>K</i>_SV) in excess of 10⁶ M^–1, with values increasing with oligomer length, consistent with the amplified quenching effect. The amplified quenching effect is proposed to occur due to the formation of comparatively small oligomer aggregates

Synthesis of Structurally Defined Cationic Polythiophenes for DNA Binding and Gene Delivery

Water-soluble conjugated polymers (<b>WCP</b>s) have prospective applications in the field of bioimaging, disease diagnosis, and therapy. However, the use of <b>WCP</b>s with controllability and regioregularity for bioapplications have scarcely been reported. In this work, we synthesized polythiophenes containing ester side chains (<b>P3ET</b>) via Kumada catalyst-transfer polycondensation (KCTP) and confirmed a quasi-“living” chain-growth mechanism. In addition, we obtained cationic regioregular polythiophenes (<b>cPT</b>s) by aminolysis of <b>P3ET</b> with varied chain lengths, and studied DNA binding capability and gene delivery performance. Benefiting from photocontrolled generation of intracellular reactive oxygen species (ROS), the cationic polythiophenes successfully delivered DNA into tumor cells without additional polymer species

Helical Conjugated Polyelectrolyte Aggregation Induced by Biotin–Avidin Interaction

Fluorescence correlation spectroscopy (FCS) is applied to demonstrate avidin-induced cross-linking in a system consisting of a helical anionic conjugated polyelectrolyte (<b>P1</b>) and a biotin-tetramethylrhodamine (TMR) conjugate (<b>2</b>). In a previous study, we used fluorescence spectroscopy to demonstrate that <b>2</b> binds to <b>P1</b> via intercalation of the TMR chromophore into the <b>P1</b> helix. Addition of avidin to the <b>P1</b>/<b>2</b> complex induces little change in the fluorescence of the system; however, FCS reveals a remarkable increase in the diffusion time of the <b>P1/2</b> complex in the presence of avidin. This change is attributed to supramolecular polymer aggregates produced by cross-link formation between the biotin unit of intercalated <b>2</b> and avidin. Atomic force microscopy imaging provides evidence supporting the existence of these aggregates. The highly sensitive FCS method is used to develop a novel sensor for the biotin–avidin interaction, with a detection limit of <100 pM for avidin

Enhanced Fluorescence Properties of Poly(phenylene ethynylene)-Conjugated Polyelectrolytes Designed to Avoid Aggregation

A new class of nonaggregating conjugated polyelectrolytes exhibits efficient fluorescence in aqueous solution. Analysis by optical spectroscopy and transmission electron microscopy reveals a unique structure–property correlation between oxygen substitution and aggregation

Targeted Gene Delivery to Macrophages by Biodegradable Star-Shaped Polymers

In this report, two biodegradable star-shaped polyasparamide derivatives and four analogues modified with either mannose or folic acid moiety for preferential targeting of a difficult-to-transfect immune cell type, i.e., macrophage, have been synthesized. Each of the prepared star polymers complexes with plasmid DNA to form nanosized particles featuring a core–shell-like morphology. Mannose or folate functionalized star polymers can greatly improve the transfection performance on a macrophage cell line RAW 264.7. As a result, a combination of targeting ligand modification and topological structures of gene carriers is a promising strategy for immune cells-based gene therapy

Remarkable Amplification of Polyethylenimine-Mediated Gene Delivery Using Cationic Poly(phenylene ethynylene)s as Photosensitizers

Conjugated polymers can serve as good photosensitizers in biomedical applications. However, it remains unknown whether they are phototoxic to the supercoiled structure of DNA in improving gene delivery by the photochemical internalization (PCI) strategy, which complicates the application of conjugated polymers in gene delivery. In this work, we introduced a trace amount of cationic poly­(phenylene ethynylene)­s (cPPEs) into the polymeric shell of branched polyethylenimine (BPEI)/DNA complexes, studied the photosensitization of singlet oxygen by cPPEs, and confirmed that the supercoiled DNA is undamaged by the singlet oxygen generated by the photoexcitation of cPPEs. By taking advantage of the cPPE-mediated PCI effect, we report that the addition of the trace amount of cPPEs to the outer shell of the BPEI/DNA polyplexes could greatly amplify the transfection of gene green fluorescent protein on tumor cells with the efficiency from 14 to 86% without decreasing the cell viabilities, well solving the problem with a poor transfection capability of BPEI under low DNA-loading conditions. Our strategy to employ conjugated polymers as photosensitizing agents in gene delivery systems is simple, safe, efficient, and promising for broad applications in gene delivery areas