Proteins and enzymes are versatile biomaterials for a wide range of medical applications due to their high specificity for receptors and substrates, high degradability, low toxicity, and overall good biocompatibility. Protein nanoparticles are formed by the arrangement of several native or modified proteins into nanometer‐sized assemblies. In this review, we will focus on artificial nanoparticle systems, where proteins are the main structural element and not just an encapsulated payload. While under natural conditions, only certain proteins form defined aggregates and nanoparticles, chemical modifications or a change in the physical environment can further extend the pool of available building blocks. This allows the assembly of many globular proteins and even enzymes. These advances in preparation methods led to the emergence of new generations of nanosystems that extend beyond transport vehicles to diverse applications, from multifunctional drug delivery to imaging, nanocatalysis and protein therapy.
Biopolymer-based drug delivery systems have gained considerable attention in the field of nanomedicine. In this study, a protein–polysaccharide conjugate was synthesized by covalent conjugation of the enzyme horseradish peroxidase (HRP) with acetalated dextran (AcDex) via a thiol exchange reaction. The resulting bioconjugate shows a dual-responsive behavior in acidic and reductive environments to achieve a controlled release of drugs. The self-assembly of this amphiphilic HRP–AcDex conjugate allows the encapsulation of prodrug indole-3-acetic acid (IAA) into the hydrophobic polysaccharide core. Under slightly acidic conditions, the acetalated polysaccharide reverts to its native hydrophilic form, which triggers the disassembly of micellar nanoparticles and the release of the encapsulated prodrug. The conjugated HRP further activates the prodrug by oxidation of IAA into cytotoxic radicals, which leads to cellular apoptosis. The results indicate that the HRP–AcDex conjugate in combination with IAA has great potential to be used as a novel enzyme prodrug therapy for cancer treatment.
The synthesis and physicochemical characterization of supramolecular polymers with tunable assembly profiles offer exciting opportunities, involving the development of new biomedical carriers. Because synthetic nanocarriers aim to transport substances across or toward cellular membranes, we evaluated the interactions of amphiphilic peptide-based supramolecular polymers with lipid bilayers. Here, we focused on nanorod-like supramolecular polymers, obtained from two C 3 -symmetric dendritic peptide amphiphiles with alternating Phe/His sequences, equipped with a peripheral tetraethylene glycol dendron (C3-PH) or charged ethylenediamine end groups (C3-PH+). Triggered by pH changes, these amphiphiles assemble reversibly. Our results show that the supramolecular polymers have an impact on the lipid order in model membranes. Changes in the lipid order were observed depending on the charge state of the amphiphilic building blocks, as well as the chemical composition and physical properties of the bilayer. Furthermore, we further performed cell viability assays with the C3-PH+ and C3-PH supramolecular polymers. For C3-PH, the cell viability and extent of proliferation were decreased and the membrane permeability was enhanced, indicating a strong interaction of the polymer with cellular membranes. The results have implications for the design of novel pH-switchable supramolecular drug carriers and delivery vehicles that can respond to an altered microenvironment of tumorous or inflamed tissue.
Proteine und Enzyme sind äußerst vielseitige Biomaterialien, die aufgrund ihrer hohen Spezifität für Rezeptoren und Substrate, ihrer Abbaubarkeit, geringen Toxizität und insgesamt guten Biokompatibilität hervorragend für ein breites Spektrum medizinischer Anwendungen geeignet sind. Durch die Anordnung mehrerer nativer oder modifizierter Proteine zu nanometergroßen Protein‐Nanopartikeln können zusätzliche vorteilhafte Eigenschaften wie eine erhöhte Stabilität im Blutstrom erreicht werden. In diesem Aufsatz konzentrieren wir uns auf künstliche Nanopartikelsysteme, bei denen Proteine das Hauptstrukturelement sind und nicht nur als eingeschlossene Wirkstoffe transportiert werden. Während unter natürlichen Bedingungen lediglich bestimmte Proteine definierte Aggregate und Nanopartikel bilden, können durch chemische Modifikationen oder Veränderungen in der physikalischen Umgebung Nanopartikel aus vielen verschiedenen globulären Proteinen und Enzymen hergestellt werden. Fortschritte bei den Herstellungsmethoden von proteinbasierten Nanopartikeln haben zu einer neuen Generation von Nanosystemen geführt, die über einfache Wirkstofftransporter hinausgehen und vielfältige Anwendungen ermöglichen, wie z.B. gezielte Arzneimittelabgabe, Theranostik, Nanokatalyse und Proteintherapie.
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