A Facile Way of Modifying Layered Double Hydroxide Nanoparticles with Targeting Ligand-Conjugated Albumin for Enhanced Delivery to Brain Tumour Cells

Active targeting of nanoparticles (NPs) for cancer treatment has attracted increasing interest in the past decades. Various ligand modification strategies have been used to enhance the targeting of NPs to the tumor site. However, how to reproducibly fabricate diverse targeting NPs with narrowly changeable biophysiochemical properties remains as a major challenge. In this study, layered double hydroxide (LDH) NPs were modified as a target delivery system. Two brain tumor targeting ligands, i.e., angiopep-2 and rabies virus glycoprotein, were conjugated to the LDH NPs via an intermatrix protein moiety, bovine serum albumin (BSA), simultaneously endowing the LDHs with excellent colloidal stability and targeting capability. The ligands were first covalently linked with BSA through the heterobifunctional cross-linker sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate. Then, the ligand-linked BSA and pristine BSA were together coated onto the surface of LDHs through electrostatic interaction, followed by cross-linking with the cross-linker glutaraldehyde to immobilize these BSAs on the LDH surface. In this way, we are able to readily prepare colloidally stabilized tumor-targeted LDH NPs. The targeting efficacy of the ligand-conjugated LDH delivery system has been evidenced in the uptake by two neutral cells (U87 and N2a) compared to unmodified LDHs. This new approach provides a promising strategy for rational design and preparation of target nanoparticles as a selective and effective therapeutic treatment for brain tumors.