Sialic acid is a fundamental component of the tumor microenvironment, modulates cell-cell and cell-extracellular matrix interactions and is associated with bad prognosis and clinical outcomes in different cancers. Capitalizing on the ability of boric acid to form cyclic esters with diols, in this work, we design self-assembled multi-micellar colloidal systems of an amphiphilic poly(vinyl alcohol)-g-poly(methyl methacrylate) copolymer surface-modified with boric acid for the active targeting of solid tumors that overexpress sialic acid. Nanoparticles display sizes in the 100-200 nm range and a spherical morphology, as determined by dynamic light scattering and high resolution-scanning electron microscopy, respectively. The uptake and anti-proliferative activity are assessed in 2D and 3D models of rhabdomyosarcoma in vitro. Surface boration increases the nanoparticle permeability and uptake, especially in rhabdomyosarcoma spheroids that overexpress sialic acid to a greater extent than 2D cultures. The biodistribution of non-borated and borated nanoparticles upon intravenous injection to a subcutaneous rhabdomyosarcoma murine xenograft model confirm a statistically significant increase in the intertumoral accumulation of the modified nanocarriers with respect to the unmodified counterparts and a sharp decrease in major clearance organs such as the liver. Overall, our results highlight the promise of these borated nanomaterials to actively target hypersialylated solid tumors.
Keywords: Active sialic acid targeting; Boric acid complexation; Rhabdomyosarcoma; Self-assembled amphiphilic poly(vinyl alcohol)-based nanoparticles; Sialic acid overexpression; Solid pediatric tumors; Tyrosine kinase inhibitors.
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