Early detection of malignant lesions and targeted therapy are major challenges for reducing cancer mortality and improving the quality of life of patients. Nanomedicine offers tools to overcome the limitations of conventional diagnostic modalities and cancer treatments. In particular, harmonic nanoparticles (HNPs) exhibit strong non-linear optical responses, generating second and third harmonic signals under ultrafast laser irradiation, making them photostable probes for bio-imaging applications. Functionalization of HNPs enables their integration into multimodal imaging and targeted therapy through the conjugation of i) targeting ligands for the selective recognition of cancer cells, ii) photocaged drugs for spatiotemporally controlled release of therapeutic payloads, and iii) additional contrast agents for multimodal imaging capabilities. Active targeting relies on the molecular recognition of specific biomarkers overexpressed by cancer cells and tumor-associated cells. The development of targeted NP-based therapies depends on the design of functionalization pathways allowing for stable anchoring and optimal display of molecular recognition motifs at the NP surface. Among the variety of receptors overexpressed across multiple cancer types, the epidermal growth factor receptor (EGFR) stands as a target of choice for cancer therapies due to its association with numerous tumors. Photo-responsive nanocarriers further enable on-demand release of therapeutic compounds upon exposure to light irradiation at specific wavelengths, exploiting photochemical reactions such as bond cleavage in coumarin (CM)-based linkers. In this project, we developed a robust coating strategy for the silanization of lithium niobate (LiNbO3, LNO) HNPs using a water-in-oil reverse microemulsion method. Subsequent surface functionalization with short peptide derivatives enabled the introduction of reactive functionalities, including azides and carboxylic acids, at the NP surface, providing handles for decoration with anti-EGFR targeting ligands. We first immobilized full-length anti-EGFR antibodies by copper-free click chemistry, and then explored the conjugation of affibodies and nanobodies via thiol-based strategies. Given the high non-specific adsorption and predominantly non-covalent immobilization observed with these types of targeting ligands, we shifted to anti-EGFR aptamers. These oligonucleotide ligands combine antibody-like affinity while being smaller, more stable and more easily produced. Several conjugation strategies were implemented, including amide bond coupling, thiol-based chemistry, neutravidin-biotin interaction and copper-free click chemistry. We also achieved multi-functionalization of the HNPs with anti-EGFR aptamers and photocaged anti-cancer drugs chlorambucil and erlotinib, allowing decoupled cancer cell targeting and controlled payload release. Preliminary in vitro evaluation suggests receptor-mediated endocytosis of the aptamer-functionalized HNPs in EGFR+ cells, and future work will compare cell lines expressing different EGFR levels. The long-term perspective of the project is to deliver multifunctional HNPs as theranostic systems. By combining targeting ligands, photo-releasable drugs and imaging probes, these nanocarriers could unite early detection and in vivo cancer treatment.