Co-Assembled Nanoparticles toward Multi-Target Combinational Therapy of Alzheimer's Disease by Making Full Use of Molecular Recognition and Self-Assembly.

The complex pathologies in Alzheimer's disease (AD) severely limit the effectiveness of single-target pharmic interventions, thus necessitating multi-pronged therapeutic strategies. While flexibility is essentially demanded in constructing such multi-target systems, for achieving optimal synergies and also accommodating the inherent heterogeneity within AD. Utilizing the dynamic reversibility of supramolecular strategy for conferring sufficient tunability in component substitution and proportion adjustment, amphiphilic calixarenes are poised to be a privileged molecular tool for facilely achieving function integration. Herein, taking ß-amyloid (Aß) fibrillation and oxidative stress as model combination pattern, a supramolecular multifunctional integration is proposed by co-assembling guanidinium-modified calixarene with ascorbyl palmitate and loading dipotassium phytate within calixarene cavity. Serial pivotal events can be simultaneously addressed by this versatile system, including 1) inhibition of Aß production and aggregation, 2) disintegration of Aß fibrils, 3) acceleration of Aß metabolic clearance, and 4) regulation of oxidative stress, which is verified to significantly ameliorate the cognitive impairment of 5×FAD mice, with reduced Aß plaque content, neuroinflammation, and neuronal apoptosis. Confronted with the extremely intricate clinical realities of AD, the strategy presented here exhibits ample adaptability for necessary alterations on combinations, thereby may immensely expedite the advancement of AD combinational therapy through providing an exceptionally convenient platform.

Protein-imprinted polymer with immobilized assistant recognition polymer chains.

Here we introduce a new method for preparing a protein-imprinted polymer with immobilized assistant recognition polymer chains as an additional element of monomer to create effective recognition sites. In this work the bovine serum albumin was used as template and the template protein was selectively assembled with immobilized assistant recognition polymer chains from their library, numerous limited length polymer chains with randomly distributed recognition sites and immobilizing sites. These assemblies of protein and immobilized assistant recognition polymer chains would be adsorbed by the macro porous adsorbent spheres and immobilized by cross-linking polymerization. After removing the template, binding sites that were complementary to the target protein in size, shape and position of recognition groups were exposed, and their confirmation was preserved by the cross-linked structure. The synthesized imprinted polymer was used to adsorb BSA from protein mixtures, and showed a high selectivity.