Lectin-conjugated pH-responsive mesoporous silica nanoparticles for targeted bone cancer treatment

TL;DR

This study presents a multifunctional, targeted, pH-responsive mesoporous silica nanoparticle system conjugated with lectin for selective bone cancer treatment, significantly improving efficacy and reducing toxicity.

Contribution

Developed a novel nanoplatform combining pH-responsive drug release and targeted delivery using lectin conjugation for bone cancer therapy.

Findings

High internalization into osteosarcoma cells

Near 100% tumor cell death with low toxicity to healthy cells

Enhanced antitumor effect compared to free drug

Abstract

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 pHresponsive 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 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.