Development of nanobioconjugates for phototheranostics: from anticancer photodynamic therapy to regenerative medicine

Phototherapies exploit the ability of selected molecules to absorb and convert light energy into therapeutic effects, enabling minimally invasive treatments with precise spatial and temporal control. Among these approaches, Photodynamic Therapy (PDT) and Photothermal Therapy (PTT) have emerged as leading strategies in anticancer treatment. PDT relies on photosensitisers activated by light to produce reactive oxygen species (ROS), which induce oxidative damage and cell death. In contrast, PTT uses light-absorbing materials that convert near-infrared (NIR) light into heat, leading to localised tumour ablation. Despite their promise, both techniques face limitations, including poor solubility of therapeutic agents, suboptimal photophysical performance, and limited targeting specificity. This PhD project addresses these challenges through the development of multifunctional theranostic nanobioconjugates that integrate chemical and biological components to enhance the precision and efficacy of phototherapies. Combining synthetic chemistry, photophysics, and bioengineering, advanced systems were designed and evaluated at molecular and nanoscale levels for applications in PDT and regenerative medicine. To improve organic photosensitisers, two main strategies were implemented: covalent conjugation with fullerene moieties to optimise light-harvesting and energy-transfer properties, and incorporation of subcellular targeting domains to enhance localisation and selectivity. Both approaches significantly improved photophysical behaviour and biological outcomes. Beyond oncology, carbon nanotube-protein hybrids were developed as photoresponsive platforms for regenerative medicine. Their heating capacity was finely controlled under low NIR irradiation to stimulate intracellular heat-mediated tissue regeneration, yielding promising in vivo results in Hydra vulgaris. To overcome delivery issues of hydrophobic photosensitisers, protein- and virus-based nanocarriers were engineered. Oligothiophene sensitisers conjugated to human serum albumin formed stable phototheranostic systems, while a genetically modified M13 bacteriophage targeting neuroblastoma demonstrated high selectivity and efficacy in GD2-positive models. Overall, this work establishes a versatile framework for next-generation photoactive nanobioconjugates, advancing the frontiers of light-driven therapies in modern nanomedicine.