Michal Kolitz-Domb

Engineering of Superparamagnetic Core–Shell Iron Oxide/N-Chloramine Nanoparticles for Water Purification

In this study, we describe the synthesis and characterization of superparamagnetic core-shell iron oxide (IO)/N-halamine antibacterial nanoparticles (NPs). For this purpose, superparamagnetic IO core NPs were coated with cross-linked polymethacrylamide (PMAA) by surfactant-free dispersion copolymerization of methacrylamide and N,N-methylenebis(acrylamide) in an aqueous continuous phase. The effect of the polymerization process on the chemical composition, size, shape, crystallinity, and magnetic properties of the IO/PMAA NPs was elucidated. Conversion of the core-shell IO/PMAA NPs into their N-halamine form, IO/PMAA-Cl, was accomplished using a chlorination reaction with sodium hypochlorite. The influence of chlorination on the shape, crystallinity, and magnetic properties of the IO/PMAA NPs was studied. The IO/PMAA-Cl NPs demonstrated excellent antibacterial activity against Gram-negative and Gram-positive bacteria. Finally, the chlorination recharging capabilities of the NPs and their potential for use in the purification of water containing bacteria were demonstrated with magnetic columns packed with the IO/PMAA-Cl NPs.

Synthesis and characterization of bioactive conjugated near-infrared fluorescent proteinoid-poly(L-lactic acid) hollow nanoparticles for optical detection of colon cancer.

Colon cancer is one of the major causes of death in the Western world. Early detection significantly improves long-term survival for patients with colon cancer. Near-infrared (NIR) fluorescent nanoparticles are promising candidates for use as contrast agents for tumor detection. Using NIR offers several advantages for bioimaging compared with fluorescence in the visible spectrum: lower autofluorescence of biological tissues and lower absorbance and, consequently, deeper penetration into biomatrices. The present study describes the preparation of new NIR fluorescent proteinoid-poly(L-lactic acid) (PLLA) nanoparticles. For this purpose, a P(EF-PLLA) random copolymer was prepared by thermal copolymerization of L-glutamic acid (E) with L-phenylalanine (F) and PLLA. Under suitable conditions, this proteinoid-PLLA copolymer can self-assemble to nanosized hollow particles of relatively narrow size distribution. This self-assembly process was used for encapsulation of the NIR dye indocyanine green. The encapsulation process increases significantly the photostability of the dye. These NIR fluorescent nanoparticles were found to be stable and nontoxic. Leakage of the NIR dye from these nanoparticles into phosphate-buffered saline containing 4% human serum albumin was not detected. Tumor-targeting ligands such as peanut agglutinin and anticarcinoembryonic antigen antibodies were covalently conjugated to the surface of the NIR fluorescent P(EF-PLLA) nanoparticles, thereby increasing the fluorescent signal of tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent P(EF-PLLA) nanoparticles was demonstrated in a chicken embryo model. In future work, we plan to extend this study to a mouse model, as well as to encapsulate a cancer drug such as doxorubicin within these nanoparticles for therapeutic applications.

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

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.

Engineering of New UV-Blocking Hollow Proteinoid Nanoparticles of Narrow Size Distribution Containing All-trans Retinoic Acid for Biomedical Applications

All-trans retinoic acid (at-RA), the most active form of vitamin A, is known to be highly beneficial in dermatology. At-RA can reduce acne vulgaris symptoms and improve the skin appearance significantly. Moreover, at-RA is a useful treatment for different skin diseases and for several types of cancer. However, it is extremely sensitive when exposed to ultraviolet (UV) light, due to conjugated double bonds that comprise its chemical structure. In order to increase the benefits of topical use of at-RA, a new drug carrier encapsulating and protecting at-RA from light-dependent degradation, is designed and presented here. Proteinoids are biocompatible polymers made from amino acids by thermal step-growth polymerization. These polymers form hollow nanoparticles in an aqueous solution by a simple selfassembly process, during which suitable molecules may be encapsulated within the particles. Thus, newly designed UV-absorbing proteinoids were utilized to encapsulate at-RA acid. New proteinoids were synthesized by thermal stepgrowth polymerization of glutamic acid, phenyl alanine and tyrosine in absence or presence of the UV absorber paraaminobenzoic acid. The proteinoids were of relatively high molecular weights and narrow molecular weight distributions (42-84 kDa, PDIs of 1.02-1.12). At-RA, was then successfully encapsulated (up to 20%) within the self-assembled proteinoid nanoparticles dispersed in an aqueous continuous phase. The proteinoid nanoparticles were able to protect the at-RA from light dependent degradation up to 94% over 24 h, while under similar conditions free at-RA degraded entirely over 3 h. The study also indicates that both the hollow and retinoic acid-filled particles are non-toxic and cellpermeable in HaCaT cells, a human epithelial cell line. The study suggests that at-RA-filled proteinoid nanoparticles protect at-RA from light-dependent degradation, offering significant advantage over free at-RA. Therefore, the optimal proteinoid particles chosen may potentially be used for acne vulgaris treatment as well as other biomedical applications requiring UV-protected retinoic acid.