Controlled design and construction of multifunctional nanoparticles by molecular self-assembly

Controlled design of nanoparticles (NPs) displaying multiple functionalities is of great interest to many applications such as targeted drug or gene delivery, diagnostic imaging, cancer theranostics, delivery of protein therapeutics, sensing chemical and biomolecular analytes in complex environments, and design of future soldier protective clothing resembling a second skin. Current methods of synthesizing multifunctional nanoparticles (MNPs) typically involve sequential chemical processing of NPs; for example, drug-encapsulated NPs are first formed, followed by surface modifications involving the sequential conjugation of ligands to provide other functionalities such as targeting, responsiveness to stimuli, etc. We describe an alternate flexible approach to constructing MNPs employing the machinery of molecular self-assembly, starting with individually functionalized amphiphilic block copolymers. The commercially available polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer is used as the building block for illustrative purposes and functionalities are provided by other chemical moieties conjugated to it via degradable linkers. For demonstrative purposes, we have chosen folic acid (a targeting ligand), bovine serum albumin (resembling a therapeutic protein), and gadolinium (a MRI contrast agent) as the functionalities, but the choice of functionalities is not limited. The self-assembly of the conjugated block copolymers is induced by solvent polarity control, resulting in the production of MNPs. Quantitative determination of the amount of each conjugated functionality is done using spectrophotometry, which shows that the composition of the MNP is controlled by the composition of the precursor functionalized block copolymers and that self-assembly preserves the compositional control. The size of the MNP can be controlled by adding a second block copolymer. The combination of the ability to introduce multiple functionalities, vary the relative proportion of functionalities, and control the nanoparticle size, all independent of one another, renders the self-assembly approach uniquely efficient for producing interesting multifunctional nanoparticles for numerous applications.