Well‐Defined Protein‐Based Supramolecular Nanoparticles with Excellent MRI Abilities for Multifunctional Delivery Systems

Abstract

Protein‐based nanoparticles are widely used for effective biomedical applications. The objective of this work is to design series of magnetic resonance imaging (MRI)‐visible cationic supramolecular nanoparticles (PGEA@BSA‐Ad/Gd3+) based on bovine serum albumin (BSA) and β‐cyclodextrin‐cored star ethanolamine‐functionalized poly(glycidyl methacrylate) (CD‐PGEA) in the presence of Gd3+ ions for multifunctional delivery systems. CD‐PGEA is prepared via atom transfer radical polymerization and ring‐opening reaction. It is found that in the absence of Gd3+ ions, CD‐PGEA does not well interact with adamantine‐modified BSA (BSA‐Ad). The well‐defined PGEA@BSA‐Ad/Gd3+ supramolecular nanoparticles could be produced through the synergistic actions of the host–guest and electrostatic self‐assemblies by mixing aqueous solutions of CD‐PGEA, BSA‐Ad, and Gd3+. In comparison with CD‐PGEA assembly units, such kinds of uniform PGEA@BSA‐Ad/Gd3+ supramolecular nanoparticles exhibit better pDNA condensation ability, lower cytotoxicity, higher gene transfection, and easier cellular uptake. In addition, PGEA@BSA‐Ad/Gd3+ also produces outstanding MRI abilities, much better than Magnevist (Gd‐diethylenetriaminepentacetate acid). The present design of protein–polymer supramolecular nanoparticles with MRI contrast agents would provide a new way for multifunctional gene/drug delivery systems.

BSA-assisted synthesis of ultrasmall gallic acid–Fe(III) coordination polymer nanoparticles for cancer theranostics

“…Therefore, BSA is widely used as a surfactant to control the synthesis of transition-metal ion-based NPs, a process similar to the biomineralization observed in nature. 24 BSA was first used by Burt et al to prepare gold NPs using direct conjugation methods. 25 Several kinds of noble metals, 26 metal alloys, 27 and metal sulfide NPs 28 have also been created using BSA as the surfactant.…”

Oxidation‐Responsive Nanoassemblies for Light‐Enhanced Gene Therapy

“…As shown in Figure a and Figure S4a (Supporting Information), in comparison to commercially available branched polyethylenimine (PEI, 25 kDa, golden standard), both CPs and CPAs demonstrated much lower cytotoxicity in 4T1, A549, and HEK 293 cell lines. The low cytotoxicity could be attributed to the nontoxic CD units and the abundant hydroxyl groups in the CPs . The relative cell viabilities of all groups decreased with the increasing N/P ratio (Figure a and Figure S4a, Supporting Information), which could be ascribed to the excessive free polycations at high N/P ratios.…”

“…With the increasing N/P ratios, all complexes show slightly decrease in hydrodynamic particle sizes and increase in zeta potentials, which are the typical behaviors of polycations‐based gene delivery systems . Particle sizes of CP/pDNA and CPA/pDNA complexes are below 250 nm, which are suitable for cellular uptake . The morphologies of the nanoparticles were further captured via AFM.…”

“…CD‐PGMA polymers with four arms were produced via atom transfer radical polymerization (ATRP) using the initiator CD‐Br 4 with four initiation sites . CD‐PGMA‐1 ( M n = 7.4 × 10 3 g mol −1 , M w / M n = 1.35) and CD‐PGMA‐2 ( M n = 1.2 × 10 4 g mol −1 , M w / M n = 1.38) were synthesized by adjusting the monomer feed ratio.…”

“…Compared with CPA‐1/pDNA complexes, the CPA‐2/pDNA complexes exhibit higher pDNA binding ability, which can be inferred from the more positive charges of CPA‐2/pDNA complexes. More importantly, suitable positive charges can benefit the adhesion of polycation/pDNA complexes to negatively charged cell membranes to facilitate their cellular uptake process …”