Engineered Narrow Size Distribution High Molecular Weight Proteinoids, Proteinoid-Poly(L-Lactic Acid) Copolymers and Nano/Micro-Hollow Particles for Biomedical Applications

Abstract

Proteinoids are unusual polymers formed by thermal condensation of amino acids. Several types of proteinoids made of one to three different amino acids, in absence or presence, of low molecular weight poly(L-lactic acid) (PLLA), were synthesized. The polymerization kinetics, molecular weights and physical and mechanical properties of these proteinoids were elucidated. The ability to obtain several high-MW durable proteinoids, by using different amino acids as building blocks, along with incorporating PLLA in their structure, yields a new perspective of biodegradable polymers and polymer particles. Under suitable gentle conditions, the proteinoids can self-assemble to form nanoand micron-sized hollow particles of relatively narrow size distribution. This self-assembly process was used for encapsulation of different molecules within the produced proteinoid particles. One of the encapsulated materials used was indocyanine green (ICG), a known and FDA-approved near-IR dye used for medical cancer diagnosis. The ICG-encapsulated proteinoid particles were tested for biodistribution in mice. The proteinoid particles are nontoxic and stable; hence, they may be excellent candidates for various biomedical applications, e.g., cell labeling and separation, controlled release, drug targeting, etc. Scheme 1: Thermal polymerization of amino acids through pyroglutamic acid catalysis. Journal of Nanomedicine & Nanotechnology J o u rna l of N a n o m ed icine & N a n o te chnolo g y

Engineering of New Proteinoids and Proteinoid Nanoparticles of Narrow Size Distribution for Anti-fog Applications

“…The synthesized proteinoids were of relatively high molecular weights, in the range of 57-68 kDa with narrow polydispersity index (PDI) in the range of 1.04-1.07. This indicates that the simple thermal polymerization procedure used here provides relatively long polymer chains with a very narrow PDI, as already reported in previous studies of our group [4][5][6][7]19]. Furthermore, Table 2 shows that all proteinoids exhibit optical activity, although the monomers are known to racemize during the thermal process [20].…”

“…Proteinoid particles were prepared by a self-assembly mechanism [4][5][6][7]13]. Briefly, 100 mg of the dried proteinoid were added to 10 mL of 10 −5 N NaCl solution.…”

“…In addition, when the self-assembly procedure is performed in the presence of a suitable molecule, a proteinoid particle containing the molecule is formed [6]. Previous studies of proteinoids in our group presented dye and drug-filled proteinoid nanoparticles [4][5][6][7].…”

“…Proteinoids, made from natural amino acids, are non-toxic, non-immunogenic and biodegradable [7]. Following their synthesis, the proteinoids can self-assemble to form hollow nano or microparticles (NPs or MPs) due to the hydrophilic/ hydrophobic character of the different functional groups in the random polymer backbone [5]. When proteinoids are self-assembled in suitable conditions, the hydrophobic residues form a hydrophobic core in the inner side of the particle, in order to minimize their contact with water, while the hydrophilic groups remain on the outer shell of the particle and form hydrogen bonds with the water continuous phase.…”

“…Fox and coworkers discovered these polymers in the previous century while studying the origin of life [1][2][3]. Proteinoids can be used for many applications, such as drug delivery and diagnosis of diseases [4][5][6][7]. Proteinoids, made from natural amino acids, are non-toxic, non-immunogenic and biodegradable [7].…”