Self-assembly in situ, where synthetic molecules are programmed to organize in a complex environment can be a unique strategy to influence cellular functions. Here we present oligothiophene analogues that target, locate and dynamically self-report their supramolecular behavior within the confinement of a cell. Through the recognition of their chemical structure, we show that the cell provides different pathways for self-assembly that are traced with fluorescence microscopy. Their molecular organization emits in distinct fluorescent bands and the control each form is achieved by time, temperature as well as the use of the intracellular transport inhibitor, bafilomycin A1. We show the importance of both intrinsic and extrinsic factors for self-organization and the potential of such a platform toward developing synthetic functional components within living cells.
In osteoporosis, bone structure can be improved by the introduction of therapeutic molecules inhibiting bone resorption by osteoclasts. Here, biocompatible hydrogels represent an excellent option for the delivery of pharmacologically active molecules to the bone tissue because of their biodegradability, injectability, and manifold functionalization capacity. The present study reports the preparation of a multifunctional hybrid hydrogel from chemically modified human serum albumin and rationally designed DNA building blocks. The hybrid hydrogel combines advantageous characteristics, including rapid gelation through DNA hybridization under physiological conditions and a self-healing and injectable nature with the possibility of specific loading and spatiotemporally controlled release of active proteins, making it an advanced biomaterial for the local treatment of bone diseases, for example, osteoporosis.
We report a bioinspired multifunctional albumin derived polypeptide coating comprising grafted poly(ethylene oxide) chains, multiple copies of the HIV TAT derived peptide enabling cellular uptake as well as mitochondria targeting triphenyl-phosphonium (TPP) groups. Exploring these polypeptide copolymers for passivating gold nanoparticles (Au NPs) yielded (i) NIR-emitting markers in confocal microscopy and (ii) photo-thermal active probes in optical coherence microscopy. We demonstrate the great potential of such multifunctional protein-derived biopolymer coatings for efficiently directing Au NP into cells and to subcellular targets to ultimately probe important cellular processes such as mitochondria dynamics and vitality inside living cells.
Organelle-targeted photosensitization represents a promising approach in photodynamic therapy where the design of the active photosensitizer (PS) is very crucial. In this work, we developed a macromolecular PS with multiple copies of mitochondria-targeting groups and ruthenium complexes that displays highest phototoxicity toward several cancerous cell lines. In particular, enhanced anticancer activity was demonstrated in acute myeloid leukemia cell lines, where significant impairment of proliferation and clonogenicity occurs. Finally, attractive two-photon absorbing properties further underlined the great significance of this PS for mitochondria targeted PDT applications in deep tissue cancer therapy.