Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, the most effective way to deliver drugs specifically to mitochondria is by covalent linking a lipophilic cation such as an alkyltriphenylphosphonium moiety to a pharmacophore of interest. Other delocalized lipophilic cations, such as rhodamine, natural and synthetic mitochondria-targeting peptides, and nanoparticle vehicles, have also been used for mitochondrial delivery of small molecules. Depending on the approach used, and the potentials of cell and mitochondrial membranes, more than 1000-fold higher mitochondrial concentration can be achieved. Mitochondrial targeting has been developed to study mitochondrial physiology and dysfunction and the interaction between mitochondria and other subcellular organelles and for treatment of a variety of diseases such as neurodegeneration and cancer. In this review, we discuss efforts to target small-molecule compounds to mitochondria for probing mitochondria function, as diagnostic tools and potential therapeutics. We describe the physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes and sensors, and examples of mitochondrial targeting of bioactive compounds. Finally, we review published attempts to apply mitochondria-targeted agents for the treatment of cancer and neurodegenerative diseases.

In this work, we report a study of long-chain zwitterionic poly(sulfobetaine methacrylate) (pSBMA) surfaces grafted via atom transfer radical polymerization (ATRP) for their resistance to bacterial adhesion and biofilm formation. Previously, we demonstrated that p(SBMA) is highly resistant to nonspecific protein adsorption. Poly(oligo(ethylene glycol) methyl ether methacrylate) (pOEGMA) grafted surfaces were also studied for comparison. Furthermore, we quantify how surface grafting methods will affect the long-term biological performance of the surface coatings. Thus, self-assembled monolayers (SAMs) of alkanethiols with shorter-chain oligo(ethylene glycol) (OEG) and mixed SO 3 − /N + (CH 3 ) 3 terminated groups were prepared on gold surfaces. The short-term adhesion (3 h) and the long-term accumulation (24 h or 48 h) of two bacterial species (Gram-positive Staphylococcus epidermidis and Gram-negative Pseudomonas aeruginosa) on these surfaces were studied using a laminar flow chamber. Methyl (CH 3 ) SAM on gold and a bare glass were chosen as references. p(SBMA) reduced short-term adhesion of S. epidermidis and P. aeruginosa relative to glass by 92% and 96%, respectively. For long-term biofilm formation, qualitative images showed that p(SBMA) dramatically reduced biofilm formation of S. epidermidis and P. aeruginosa as compared to glass.

In this work, we report a systematic study of zwitterionic poly(carboxybetaine methacrylate) (pCBMA) grafted from glass surfaces via atom transfer radical polymerization (ATRP) for their resistance to long-term bacterial biofilm formation. Results show that pCBMA-grafted surfaces are highly resistant to nonspecific protein adsorption (fibrinogen and undiluted blood plasma) at 25, 30 and 37 °C. Long-term (over 24 h) colonization of two bacterial strains (Pseudomonas aeruginosa PAO1 and Pseudomonas putida strain 239) on pCBMA surface was studied using a parallel flow cell at 25, 30 and 37 °C. Uncoated glass cover slips were chosen as the positive reference. Results show that pCBMA coatings reduced long-term biofilm formation of P. aeruginosa up to 240 h by 95% at 25 °C and for 64 h by 93% at 37 °C, and suppressed P. putida biofilm accumulation up to 192 h by 95% at 30 °C, with respect to the glass reference. The ability of pCBMA coatings to resist non-specific protein adsorption and significantly retard bacterial biofilm formation makes it a very promising material for biomedical and industrial applications.

A crucial step in the development of implanted medical devices, in vivo diagnostics, and microarrays is the effective prevention of nonspecific protein adsorption from real-world complex media such as blood plasma or serum. In this work, a zwitterionic poly(carboxybetaine acrylamide) (polyCBAA) biomimetic material was employed to create a unique biorecognition coating with an ultralow fouling background, enabling the sensitive and specific detection of proteins in blood plasma. Conditions for surface activation, protein immobilization, and surface deactivation of the carboxylate groups in the polyCBAA coating were determined. An antibody-functionalized polyCBAA surface platform was used to detect a target protein in blood plasma using a sensitive surface plasmon resonance (SPR) sensor. A selective protein was directly detected from 100% human blood plasma with extraordinary specificity and sensitivity. The total nonspecific protein adsorption on the functionalized polyCBAA surface was very low (<3 ng/cm (2) for undiluted blood plasma). Because of the significant reduction of nonspecific protein adsorption, it was possible to monitor the kinetics of antigen-antibody interactions in undiluted blood plasma. The functionalization effectiveness and detection characteristics using a cancer protein marker candidate of polyCBAA were compared with those of the conventional nonfouling oligo(ethylene glycol)-based surface chemistry.