The materials used in cancer diagnosis and treatment have been continuously advancing, with nanomedicine revolutionizing this field. Osteosarcoma, the most common malignant bone tumor in children and adolescents, faces significant limitations in conventional treatments due to side effects and drug resistance. This study introduces a theranostic nanoprobe composed of a plasmonic gold core, a polymeric coating, and a chemotherapeutic drug for targeted therapy and simultaneous imaging of bone cancer. In the first phase, numerical simulations were conducted to examine the effects of gold nanostructure shape and size on temperature distribution patterns in photothermal therapy. Based on the results, gold nanorods with an aspect ratio of 4 ± 0.3 and a longitudinal surface plasmon resonance peak at 810 nm were identified as the optimal nanostructure. In the second phase, these optimized gold nanorods were synthesized using a seed-mediated growth method, subsequently modified with polyethylene glycol (PEG), and loaded with the chemotherapeutic agent doxorubicin (DOX). The successful DOX loading was confirmed through surface chemical modifications, with a drug-loading capacity of approximately 86.1 ± 1.1%. In the third phase, the biological performance of the modified and drug-loaded nanorods was eva‎luated at concentrations of 10, 20, and 40 µg/mL. The results demonstrated that the surface-modified nanoparticles exhibited a lower temperature increase (55 ± 5°C) compared to the unmodified variants (70 ± 10°C). Furthermore, drug release, influenced by environmental pH and laser irradiation, reached 90 ± 10% after 72 hours. The combined photothermal and chemotherapy treatment at 20 and 40 µg/mL showed the highest efficacy, inducing over 40% cell death. The micro-CT imaging capability of the gold nanoprobes was validated with a Hounsfield unit of 325. For the tissue engineering section, poly(lactic-co-glycolic acid) (PLGA) was used as the base polymer, and its composites with polycaprolactone (PCL), polylactic acid (PLA), and polyurethane (PU) were examined. The PLGA/PLA composite was identified as the optimal candidate due to its superior physical and mechanical properties. Scaffolds were fabricated using extrusion-based 3D printing, with optimized printing parameters including a speed of 50 mm/min, a nozzle diameter of 0.4 mm, and 70% porosity. Structural, mechanical, and biological assessments were conducted on the control scaffold (PLGA/PLA), Target-1 (containing gold nanoprobes), and Target-2 (containing gold nanoprobes with a chitosan hydrogel coating). The control scaffold exhibited uniform and interconnected pores of approximately 700 ± 100 µm, whereas the presence of gold nanoprobes in Target-1 increased surface roughness and reduced pore size to 400 ± 150 µm. Target-1 demonstrated superior mechanical performance, with a compressive strength of approximately 57 MPa and a high compressive modulus. In contrast, Target-2 exhibited lower compressive strength (~45 MPa) due to the chitosan coating and water absorption but provided greater flexibility (~48%). The targeted scaffolds also exhibited effective photothermal performance, reaching a core temperature of 48 ± 2°C. Additionally, controlled drug release in response to pH and laser irradiation demonstrated a favorable profile. The combined therapeutic strategies reduced MG63 cell viability to below 20%, indicating high efficacy in inducing cancer cell death. These findings contribute to the advancement of photothermal therapy, targeted drug delivery, and imaging strategies for bone cancer treatment.

شيدا لباف , احمد كرمانپور

جواد اسمعيلي

علي اصغر انصافي , فتح اله كريم زاده , انوشه زرگر خرازي