Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution

The surface of proteins is heterogeneous with sophisticated but precise hydrophobic and hydrophilic patches, which is essential for their diverse biological functions. To emulate such distinct surface patterns on macromolecules, we used rigid spherical synthetic dendrimers (polyphenylene dendrimers) to provide controlled amphiphilic surface patches with molecular precision. We identified an,. I optimal spatial arrangement of these patches on certain dendrimers that enabled their interaction with human adenovirus 5 (Ads). Patchy dendrimers bound to the surface of Ads formed a synthetic polymer corona that greatly altered various host interactions of Ads as well as in vivo distribution. The dendrimer corona (1) improved the ability of Ad5-derived gene transfer vectors to transduce cells deficient for the primary Ad5 cell membrane receptor and (2) modulated the binding of Ads to blood coagulation factor X, one of the most critical virus host interactions in the bloodstream. It significantly enhanced the transduction efficiency of Ad5 while also protecting it from neutralization by natural antibodies and the complement system in human whole blood. Ads with a synthetic dendrimer corona revealed profoundly altered in vivo distribution, improved transduction of heart, and dampened vector sequestration by liver and spleen. We propose the design of bioactive polymers that bind protein surfaces solely based on their amphiphilic surface patches and protect against a naturally occurring protein corona, which is highly attractive to improve Ad5-based in vivo gene therapy applications

Fine-tuning the Microstructure and Photophysical Characteristics of Fluorescent Conjugated Copolymers Using Photoalignment and Liquid-crystalline Ordering

Replicating the microstructure and near-unity excitation energy transfer efficiency in natural light-harvesting complexes (LHCs) remains a major challenge for synthetic energy-harvesting devices. Biological photosynthesis can spontaneously regulate the active ensembles of involved energy absorbing and funnelling chlorophyll-containing proteins in response to fluctuating sunlight. Here we utilize liquid crystalline (LC) ordering to fine-tune the polymer packing and photophysical properties in liquid crystalline conjugated polymer (LCCP) films for LHC biomimicry and optimizing photoluminescence quantum efficiency (PLQE). We show that the long-range orientational ordering present in a LC phase of poly(9,9-dioctylfluorene-co-benzothiadiazole) (F8BT) stabilizes a small fraction of randomly-oriented F8BT nanocrystals dispersed in an amorphous matrix of disordered F8BT chains, hence resembling a self-doped host-guest system whereby excitation energy funnelling and PLQE are reinforced significantly by three-dimensional donor-to-acceptor Forster resonance energy transfer (FRET) and dominant intrachain emission in the nano-crystalline acceptor. Furthermore, the photoalignment of nematic F8BT layers is combined to fabricate long-sought large-area-extended monodomains which exhibit >60% crystallinity and ~20 nm-long interchain packing order, whilst also promoting linearly polarized emission, a new band-edge absorption species, and an extra emissive interchain excited state. Our micro-PL spectral results support the feasibility of making use of self-doped F8BT nematic films for bio-mimicry of certain structural basis and light-harvesting properties of naturally occurring LHCs

Fine-tuning the microstructure and photophysical characteristics of fluorescent conjugated copolymers using photoalignment and liquid-crystal ordering

Replicating the microstructural basis and the near 100% excitation energy transfer efficiency in naturally occurring light-harvesting complexes (LHCs) remains challenging in synthetic energy-harvesting devices. Biological photosynthesis regulates active ensembles of light-absorbing and funneling chlorophylls in proteins in response to fluctuating sunlight. Here, use of long-range liquid crystal (LC) ordering to tailor chain orientation and packing structure in liquid crystalline conjugated polymer (LCCP) layers for bio-mimicry of certain structural basis and light-harvesting properties of LHCs is reported. It is found that long-range orientational ordering in an LC phase of poly(9,9-dioctylfluorene-co-benzothiadiazole) (F8BT) copolymer stabilizes a small fraction of randomly-oriented F8BT nanocrystals dispersed in an amorphous matrix of F8BT chains, resembling a self-doped host-guest system whereby excitation energy funneling and photoluminescence quantum efficiencies are enhanced significantly by triggering 3D donor-to-acceptor Förster resonance energy transfer (FRET) and dominant intrachain emission in the nano-crystal acceptor. Further, photoalignment of nematic F8BT layers is combined with LC orientational ordering to fabricate large-area-extended monodomains exhibiting >60% crystallinity and ≈20 nm-long interchain packing order. Remarkably, these monodomains demonstrate strong linearly polarized emission, whilst also promoting a new band-edge absorption species and an extra emissive interchain excited state as compared to the non-aligned films