Martínez Carmona, MarinaLozano Borregón, DanielColilla Nieto, MontserratVallet Regí, María Dulce Nombre2023-06-172023-06-172017-11-071742-706110.1016/j.actbio.2017.11.007https://hdl.handle.net/20.500.14352/18249RESEARCHER ID N-3992-2014 (Marina Martínez Carmona) ORCID 0000-0002-2026-6266 (Marina Martínez Carmona) RESEARCHER ID B-5081-2017 (Daniel Lozano Borregón) RESEARCHER ID N-4628-2014 (Montse Colilla Nieto) ORCID 0000-0003-1961-4160 (Montse Colilla Nieto) ORCID 0000-0001-5902-9201 (Daniel Lozano Borregón) RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí)A novel multifunctional nanodevice based in doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs) as nanoplatforms for the assembly of different building blocks has been developed for bone cancer treatment. These building blocks consists of: i) a polyacrylic acid (PAA) capping layer grafted to MSNs via an acid-cleavable acetal linker, to minimize premature cargo release and provide the nanosystem of pH-responsive drug delivery ability; and ii) a targeting ligand, the plant lectin concanavalin A (ConA), able to selectively recognize, bind and internalize owing to certain cell-surface glycans, such as sialic acids (SA), overexpressed in given tumor cells. This multifunctional nanosystem exhibits a noticeable higher internalization degree into human osteosarcoma cells (HOS), overexpressing SA, compared to healthy preosteoblast cells (MC3T3-E1). Moreover, the results indicate that small DOX loading (2.5 µg mL−1) leads to almost 100% of osteosarcoma cell death in comparison with healthy bone cells, which significantly preserve their viability. Besides, this nanodevice has a cytotoxicity on tumor cells 8-fold higher than that caused by the free drug. These findings demonstrate that the synergistic combination of different building blocks into a unique nanoplatform increases antitumor effectiveness and decreases toxicity towards normal cells. This line of attack opens up new insights in targeted bone cancer therapy. Statement of Significance The development of highly selective and efficient tumor-targeted smart drug delivery nanodevices remains a great challenge in nanomedicine. This work reports the design and optimization of a multifunctional nanosystem based on mesoporous silica nanoparticles (MSNs) featuring selectivity towards human osteosarcoma cells and pH-responsive antitumor drug delivery capability. The novelty and originality of this manuscript relies on proving that the synergistic assembly of different building blocks into a unique nanoplatform increases antitumor effectiveness and decreases toxicity towards healthy cells, which constitutes a new paradigm in targeted bone cancer therapy.spajournal articlehttps://doi.org/10.1016/j.actbio.2017.11.007https://www.elsevier.com/http://www.ucm.es/valletregigroupopen access615.46546Antitumor effectBone cancerLectinMesoporous silica nanoparticlesNanomedicinepH-responsive drug releaseSynergistic combinationTargetingIngeniería químicaMaterialesQuímica inorgánica (Química)3303 Ingeniería y Tecnología Químicas3312 Tecnología de Materiales2303 Química Inorgánica