Understanding molecular interactions and regulatory mechanisms in tumor initiation, progression, and treatment response are key requirements towards advanced cancer diagnosis and novel treatment procedures in personalized medicine. Beyond decoding the gene expression, malfunctioning and cancer-related epigenetic pathways, investigations of the spatial receptor arrangements in membranes and genome organization in cell nuclei, on the nano-scale, contribute to elucidating complex molecular mechanisms in cells and tissues. By these means, the correlation between cell function and spatial organization of molecules or molecular complexes can be studied, with respect to carcinogenesis, tumor sensitivity or tumor resistance to anticancer therapies, like radiation or antibody treatment. Here, we present several new applications for bio-molecular nano-probes and super-resolution, laser fluorescence localization microscopy and their potential in life sciences, especially in biomedical and cancer research. By means of a tool-box of fluorescent antibodies, green fluorescent protein (GFP) tagging, or specific oligonucleotides, we present tumor relevant re-arrangements of Erb-receptors in membranes, spatial organization of Smad specific ubiquitin protein ligase 2 (Smurf2) in the cytosol, tumor cell characteristic heterochromatin organization, and molecular re-arrangements induced by radiation or antibody treatment. The main purpose of this article is to demonstrate how nano-scaled distance measurements between bio-molecules, tagged by appropriate nano-probes, can be applied to elucidate structures and conformations of molecular complexes which are characteristic of tumorigenesis and treatment responses. These applications open new avenues towards a better interpretation of the spatial organization and treatment responses of functionally relevant molecules, at the single cell level, in normal and cancer cells, offering new potentials for individualized medicine.

Radiotherapy is a crucial component of cancer care, employed in the treatment of over 50% of cancer patients. Patients undergoing image-guided radiotherapy or brachytherapy routinely have inert radiotherapy (RT) biomaterials implanted into their tumors. The single function of these RT biomaterials is to ensure geometric accuracy during treatment. Recent studies have proposed that the inert biomaterials could be upgraded to ‘smart’ RT biomaterials, designed to do more than one function. Such smart biomaterials include next generation fiducial markers, brachytherapy spacers, and balloon applicators, designed to respond to stimulus and perform additional desirable functions like controlled delivery of therapy-enhancing payloads directly into the tumor sub-volume, while minimizing normal tissue toxicities. More broadly, smart RT biomaterials may include functionalized nanoparticles that can be activated to boost radiotherapy efficacy. This work reviews the rationale for smart radiotherapy biomaterials, the state-of-the-art in this emerging cross-disciplinary research area, challenges/opportunities for further research and development, and a purview of potential clinical applications. Applications covered include using smart RT biomaterials for boosting cancer therapy with minimal side effects, combining radiotherapy with immunotherapy or chemotherapy, reducing treatment time or healthcare costs, and other incipient applications.