BackgroundThe use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer owing to the negligible absorption and autofluorescence of water and other intrinsic biomolecules in this region. The main aim of the present study is to synthesize and characterize novel NIR fluorescent nanoparticles based on proteinoid and PLLA for early detection of colon tumors.MethodsThe present study describes the synthesis of new proteinoid-PLLA copolymer and the preparation of NIR fluorescent nanoparticles for use in diagnostic detection of colon cancer. These fluorescent nanoparticles were prepared by a self-assembly process in the presence of the NIR dye indocyanine green (ICG), a FDA-approved NIR fluorescent dye. Anti-carcinoembryonic antigen antibody (anti-CEA), a specific tumor targeting ligand, was covalently conjugated to the P(EF-PLLA) nanoparticles through the surface carboxylate groups using the carbodiimide activation method.Results and discussionThe P(EF-PLLA) nanoparticles are stable in different conditions, no leakage of the encapsulated dye into PBS containing 4% HSA was detected. The encapsulation of the NIR fluorescent dye within the P(EF-PLLA) nanoparticles improves significantly the photostability of the dye. The fluorescent nanoparticles are non-toxic, and the biodistribution study in a mouse model showed they evacuate from the body over 24 h. Specific colon tumor detection in a chicken embryo model and a mouse model was demonstrated for anti-CEA-conjugated NIR fluorescent P(EF-PLLA) nanoparticles.ConclusionsThe results of this study suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent P(EF-PLLA) nanoparticles over colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs such as paclitaxel and/or doxorubicin, within these biodegradable NIR fluorescent P(EF-PLLA) nanoparticles, for both detection and therapy of colon cancer.
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
Fog formation on transparent surfaces constitutes a major challenge in several optical applications, such as plastic packaging, lenses, mirrors, and windshields. To overcome this problem, we prepared and characterized durable antifog thin coatings on plastic films such as polyethylene terephthalate (PET). Proteinoids are biocompatible random polymers made of α-amino acids by thermal step-growth polymerization. Proteinoid prepolymers were prepared by adding activated double bonds to proteinoids via the Michael addition reaction. A series of thin antifog cross-linked coatings were prepared by spreading on PET films with a Mayer rod various mixtures of the proteinoid prepolymers, polyethylene glycol diacrylate, and a photoinitiator, followed by UV-curing of the dried coatings. The antifog properties of the coatings were determined by the contact angle, roughness, haze, and gloss measurements, as well as hot and cold fog tests, to examine the optical properties of the films under fog formation conditions. Mechanical properties such as adhesion, robustness, and abrasion resistance of the antifog coatings were examined by tape, knife-scratch, and sandpaper abrasion tests. The effect of coating composition, wettability, and roughness on the antifog properties of the coated PET films was elucidated. The formula was optimized, and the corresponding UV-cured antifog cross-linked thin coating exhibited transparency with good adhesion and excellent durable antifog performance.
Proteinoids, thermal polymers composed of amino acids, discovered and studied by Fox, spontaneously selfassemble in spherical structures, microspheres, which Fox presented as the protocells of life. Fox's findings opened up a scope of applicable easy-to-make protein-like particles. In recent years, interest in proteinoids has increased among nanobiomedicine research workers. These structures are suitable for biomedical applications, due to their protein-like nature, biocompatibility, non-toxicity and safety. Several new proteinoids made of a specific selection of amino acids were introduced for biomedical and agricultural industries. Several proteinoids include specific additives polymerized within their backbone, providing special chracteristics for a specific application. These proteinoids, their corresponding nanoparticles and their diverse applications are presented here, primarily focusing on proteinoids for cancer diagnostics and therapy, cosmetic and anti-fog proteinoids.
RGD sequence is a tripeptide composed of three amino acids: arginine (R), glycine (G), and aspartic acid (D). The RGD peptide has a high affinity to the integrin alpha v beta 3, which is overexpressed on the membrane of many cancer cells and is attracted to areas of angiogenesis. Proteinoids are biodegradable polymers based on amino acids which are formed by bulk thermal step-growth polymerization mechanism. Hollow proteinoid nanoparticles (NPs) may be formed via self-assembly process of the proteinoid polymers. We propose using novel RGD-based proteinoid polymers to manufacture NPs in which the RGD motif is self-incorporated in the proteinoid backbone. Such P(RGD) NPs can act both as a drug carrier (by encapsulation of a desired drug) and as a targeting delivery system. This article presents the synthesis of four RGD proteinoids with different RGD optical configurations, ( d ) or ( l ) arginine, glycine, and ( d ) or ( l ) aspartic acid, in order to determine which configuration is optimal as a drug-targeting carrier. These new RGD proteinoid polymers possess high molecular weights and molecular weight monodispersity. Homonuclear nuclear magnetic resonance methods were employed to predict the expected concentration of RGD tripeptide sequence in the polymer. Near infrared fluorescent NPs have been prepared by the encapsulation of indocyanine green (ICG) dye within the different P(RGD) NPs. The dry diameters of the hollow P(R d GD d ), P(R d GD), P(RGD), and P(RGD d ) NPs are 55 ± 13, 48 ± 9, 45 ± 11, and 42 ± 9 nm, respectively, whereas those of the ICG-encapsulated NPs were significantly higher, 141 ± 24, 95 ± 13, 86 ± 11, and 87 ± 12 nm, respectively. The ICG-encapsulated P(R d GD) NPs exhibited higher selectivity toward epithelial injury, as demonstrated using an in vitro scratch assay, because the P(R d GD) NPs accumulated in the injured area at higher concentrations when compared to other P(RGD) NPs with different chiralities. Therefore, the P(R d GD) polymer configuration is the polymer of choice for use as a targeted drug carrier to areas of angiogenesis, such as in tumors, wounds, or cuts.
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