RT Journal Article
T1 Lectin-Conjugated pH-Responsive Mesoporous Silica Nanoparticles for Targeted Bone Cancer Treatment.
A1 Martínez Carmona, Marina
A1 Lozano Borregón, Daniel
A1 Colilla Nieto, Montserrat
A1 Vallet Regí, María Dulce Nombre
AB 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 SignificanceThe 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.
PB Elsevier
SN 1742-7061
YR 2017
FD 2017-11-07
LK https://hdl.handle.net/20.500.14352/18249
UL https://hdl.handle.net/20.500.14352/18249
LA spa
NO RESEARCHER 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)
NO Unión Europea. Horizonte 2020
NO Ministerio de Economía y Competitividad (MINECO)
DS Docta Complutense
RD 19 jun 2026