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The last decade has seen an increasingly large number of studies reporting on the development of novel small organic conjugated systems for mitochondrial imaging exploiting optical signal transduction pathways. Mitochondria are known to play a critical role in a number of key biological processes, including cellular metabolism. Importantly, irregularities on their working function are nowadays understood to be intimately linked to a range of clinical conditions, highlighting the importance of targeting mitochondria for therapeutic benefits. In this work we carry out an in-depth evaluation on the progress to date in the field to pave the way for the realization of superior alternatives to those currently existing. The manuscript is structured by commonly used chemical scaffolds and comprehensively covers key aspects factored in design strategies such as synthetic approaches as well as photophysical and biological characterization, to foster collaborative work among organic and physical chemists as well as cell biologists.

With the growing crisis of the availability of effective antimicrobial treatments, the use of phototherapy has gained increasing interest as an alternative to traditional antibiotic therapy. Even though phototherapy is already used in the clinic, there is an emerging interest in new materials with enhanced antimicrobial activity triggered by light. Among the different light‐responsive materials, conjugated polymers are emerging candidates with successful application in the field of antimicrobial photodynamic and photothermal therapy. Due to their organic composition, easy processability, tailorability of physicochemical properties, and capability of reactive oxygen species (ROS) and heat generation, their use as photoresponsive agents against bacteria has greatly expanded. Conjugated polymers have been designed to interact with specific bacterial targets, and their chemical composition has been optimized to enhance ROS and/or heat generation and new cationic polymers have been developed for augmented water solubility and increased interaction with negatively charged bacteria. Herein, the use of conjugated polymers in the field of phototherapy is discussed, focusing on the different approaches that have improved their performance against bacteria and their current preclinical safety assessment.

Amphiphilic block co-polymers composed of poly(ethylene glycol)-co-poly(lactide)-co-poly(2-((tert-butoxycarbonyl)amino)-3-propyl carbonate) (PEG-pLA-pTBPC) are synthesized in monomer ratios and arrangements to enable assembly into nanoparticles with different sizes and architectures. These materials are based on components in clinical use, or known to be biodegradable, and retain the same fundamental chemistry across 'AB' and 'BAB' block architectures. In MCF7 and MDA-MB-231 breast cancer cells, nanoparticles of < 100 nm are internalized most rapidly, by both clathrin-and caveolin-mediated pathways. In THP-1 cells, polymer architecture and length of the hydrophilic block is the most important factor in the rate of internalization. The organ distributions of systemically injected nanoparticles in healthy mice indicate highest accumulation of the BAB-blocks in lungs and liver and the lowest accumulation in these organs of a methoxyPEG5000-pLA-pTBPC polymer. Conjugation of doxorubicin via a serum-stable urea linker to the carbonate regions of PEG5000-pLA-pTBPC generates self-assembling nanoparticles which are more cytotoxic in 2D, and penetrate further in 3D spheroids of triple negative breast cancer cells, than the free drug. In an aggressive orthotopic triple negative breast cancer mouse model, the methoxyPEG5000-pLA-pTBPC is of similar potency to free doxorubicin but with no evidence of adverse effects in terms of body weight.