Lectin-conjugated pH-responsive mesoporous silica nanoparticles for targeted bone cancer treatment
Open accessAbstract
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.
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Artificial materials such as synthetic liposomes and polylactic acid have been exploited as carriers.
“With the progress of science and technology, artificial materials such as synthetic liposomes and polylactic acid have been exploited as carriers in the last few years.”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [19]
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The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System
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- Authors
- Martínez-Carmona, M., Lozano, D., Colilla, M., & Vallet-Regí, M.
- Affiliations
- Universidad Complutense de Madrid (ES)
- Corresponding author
- Colilla, Montserrat
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 65
- Pages
- 393-404
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W2767616074
- Cited by
- 220
- References
- 83
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 14 · 2023: 23 · 2022: 33 · 2021: 32 · 2020: 34 · 2019: 34 · 2018: 10 · 2017: 1
- FWCI
- 7.77
- Type
- journal article
- Language
- en
- Open access
- green
- arxiv.org
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- Docta Complutense (Universidad Complutense de Madrid) (submittedVersion, other-oa)
- arXiv (Cornell University)
- Funders
- European Research Council
- Spanish Ministerio de Economía y Competitividad
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Materials Chemistry › Mesoporous Materials and Catalysis
- Keywords
- mesoporous silica nanoparticles, doxorubicin, pH-responsive drug delivery, concanavalin A, sialic acid, osteosarcoma, targeted drug delivery, tumor cell internalization, nanomedicine
- MeSH terms
- Animals, Antibiotics, Antineoplastic, Bone Neoplasms, Concanavalin A, Doxorubicin, Drug Carriers, Humans, Hydrogen-Ion Concentration, Microscopy, Fluorescence, Polysaccharides, Sialic Acids, Silicon Dioxide, X-Ray Diffraction, Porosity, 3T3 Cells, Drug Delivery Systems, Spectroscopy, Fourier Transform Infrared, Lectins, Cell Line, Tumor, Microscopy, Electron, Transmission, Mice, Nanoparticles
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