Folate-functionalized assembly of low density lipoprotein/sodium carboxymethyl cellulose nanoparticles for targeted...

In this study, well-defined folate (FA)-functionalized low density lipoproteins (LDL)/sodium carboxymethyl cellulose (CMC) nanoparticles (NP) were first formulated, utilized in tumor targeting and pH-triggered drug release. CMC was modified with FA before the preparation of NP. A model anti-tumor drug, doxorubicin (DOX), was effectively loaded into the LDL/CMC-FA NP by ionic bonding and hydrophobic interactions. To enhance non-covalent encapsulation stability, self-assembly of DOX-loaded LDL/CMC-FA NP (NP-DOX) was cross-linked by multivalent cations such as Ca²⁺ (Ca²⁺-NP-DOX). The active targeting efficiency of NP-DOX and Ca²⁺-NP-DOX was tested against KB cells (FA-receptor over-expressing cells, FR+) and A549 cells (FA-receptor negative-expressing cells, FR-), using FA non-modified DOX-loaded LDL/CMC NP (NG-DOX) as control. The competition assay proved that free FA molecules prevented the cellular uptake of the NP by competitive binding to the FA receptors on the surface of KB cells. This new pH-responsive and FA-targeted nanocarrier may be a promising efficient drug delivery system for potential cancer therapy.