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1. Self‐Assembled Peptide‐Based Biocomposites for Near‐Infrared Light Triggered Drug Release to Tumor Cells

   https://doi.org/10.1002/biot.202000128  

   Daso, Rachel E. ; Banerjee, Ipsita A. ( September 2020 , Biotechnology Journal)

   Peptide‐based nanomaterials are increasingly gaining popularity due to their specificity, biocompatibility, and biodegradability. In this work, a new multi‐layered peptide‐based biocomposite for targeting MCF‐7 breast cancer cells is developed. The amphipathic Fluorenylmethyloxycarbonyl (Fmoc)‐Leu‐Ser peptide is synthesized, which is conjugated to a tumor‐targeting peptide sequence Gly‐Cys‐Gly‐Asn‐Ser to form Fmoc‐L‐S‐G‐C‐G‐N‐S (FLS) assemblies. To the FLS assemblies, gold nanorods are then attached to develop drug delivery vehicles (DDVs). The DDVs are entrapped with the anti‐cancer drug fulvestrant. Entrapment efficiency is found to be 50.6%. Release studies indicate that irradiating the gold nanorod bound DDVs at NIR wavelength (785 nm) increases drug release by fourfold compared to assemblies that are not irradiated. These results also show higher cytotoxicity and lower cell invasion due to photo‐triggered drug release. Furthermore, distinct actin cytoskeletal changes are observed. Such novel peptide‐based gold nanorod bound DDVs demonstrate potential in dual targeting of MCF‐7 breast cancer cells.

    

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2. Mitochondrial Targeting Peptide-based Nanodelivery for Cancer Treatment

   https://doi.org/10.2174/1389203723666220520160435  

   Ehsan, Sumia ; Covarrubias-Zambrano, Obdulia ; Bossmann, Stefan H. ( October 2022 , Current Protein & Peptide Science)

   Abstract: Mitochondria are important intracellular organelles because of their key roles in cellular metabolism,proliferation, and programmed cell death. The differences in the structure and function of themitochondria of healthy and cancerous cells have made mitochondria an interesting target for drug delivery.Mitochondrial targeting is an emerging field as the targeted delivery of cytotoxic payloads andantioxidants to the mitochondrial DNA is capable of overcoming multidrug resistance. Mitochondrialtargeting is preferred over nuclear targeting because it can take advantage of the distorted metabolismin cancer. The negative membrane potential of the inner and outer mitochondrial membranes, as well astheir lipophilicity, are known to be the features that drive the entry of compatible targeting moiety,along with anticancer drug conjugates, towards mitochondria. The design of such drug nanocarrier conjugatesis challenging because they need not only to target the specific tumor/cancer site but have toovercome multiple barriers as well, such as the cell membrane and mitochondrial membrane. This reviewfocuses on the use of peptide-based nanocarriers (organic nanostructures such as liposomes, inorganic,carbon-based, and polymers) for mitochondrial targeting of the tumor/cancer. Both invitro and in vivo key results are reported. 

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3. Fluorinated peptide biomaterials

   https://doi.org/10.1002/pep2.24184  

   Sloand, Janna N. ; Miller, Michael A. ; Medina, Scott H. ( July 2020 , Peptide Science)

   Fluorinated compounds, while rarely used by nature, are emerging as fundamental ingredients in biomedical research, with applications in drug discovery, metabolomics, biospectroscopy, and, as the focus of this review, peptide/protein engineering. Leveraging the fluorous effect to direct peptide assembly has evolved an entirely new class of organofluorine building blocks from which unique and bioactive materials can be constructed. Here, we discuss three distinct peptide fluorination strategies used to design and induce peptide assembly into nano‐, micro‐, and macro‐supramolecular states that potentiate high‐ordered organization into material scaffolds. These fluorine‐tailored peptide assemblies employ the unique fluorous environment to boost biofunctionality for a broad range of applications, from drug delivery to antibacterial coatings. This review provides foundational tactics for peptide fluorination and discusses the utility of these fluorous‐directed hierarchical structures as material platforms in diverse biomedical applications.

    

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4. Metal-Assembled Collagen Peptide Microflorettes as Magnetic Resonance Imaging Agents

   https://doi.org/10.3390/molecules28072953  

   Ernenwein, Dawn ; Geisler, Iris ; Pavlishchuk, Anna ; Chmielewski, Jean ( April 2023 , Molecules)

   Magnetic resonance imaging (MRI) is a medical imaging technique that provides detailed information on tissues and organs. However, the low sensitivity of the technique requires the use of contrast agents, usually ones that are based on the chelates of gadolinium ions. In an effort to improve MRI signal intensity, we developed two strategies whereby the ligand DOTA and Gd(III) ions are contained within Zn(II)-promoted collagen peptide (NCoH) supramolecular assemblies. The DOTA moiety was included in the assembly either via a collagen peptide sidechain (NHdota) or through metal–ligand interactions with a His-tagged DOTA conjugate (DOTA-His6). SEM verified that the morphology of the NCoH assembly was maintained in the presence of the DOTA-containing peptides (microflorettes), and EDX and ICP-MS confirmed that Gd(III) ions were incorporated within the microflorettes. The Gd(III)-loaded DOTA florettes demonstrated higher intensities for the T1-weighted MRI signal and higher longitudinal relaxivity (r1) values, as compared to the clinically used contrast agent Magnevist. Additionally, no appreciable cellular toxicity was observed with the collagen microflorettes loaded with Gd(III). Overall, two peptide-based materials were generated that have potential as MRI contrast agents. 

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5. Engineered protein–iron oxide hybrid biomaterial for MRI-traceable drug encapsulation

   https://doi.org/10.1039/d2me00002d  

   Hill, Lindsay K. ; Britton, Dustin ; Jihad, Teeba ; Punia, Kamia ; Xie, Xuan ; Delgado-Fukushima, Erika ; Liu, Che Fu ; Mishkit, Orin ; Liu, Chengliang ; Hu, Chunhua ; et al ( August 2022 , Molecular Systems Design & Engineering)

   Labeled protein-based biomaterials have become popular for various biomedical applications such as tissue-engineered, therapeutic, and diagnostic scaffolds. Labeling of protein biomaterials, including with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, has enabled a wide variety of imaging and therapeutic techniques. These USPIO-based biomaterials are widely studied in magnetic resonance imaging (MRI), thermotherapy, and magnetically-driven drug delivery, which provide a method for direct and non-invasive monitoring of implants or drug delivery agents. Where most developments have been made using polymers or collagen hydrogels, shown here is the use of a rationally designed protein as the building block for a meso-scale fiber. While USPIOs have been chemically conjugated to antibodies, glycoproteins, and tissue-engineered scaffolds for targeting or improved biocompatibility and stability, these constructs have predominantly served as diagnostic agents and often involve harsh conditions for USPIO synthesis. Here, we present an engineered protein–iron oxide hybrid material comprised of an azide-functionalized coiled-coil protein with small molecule binding capacity conjugated via bioorthogonal azide–alkyne cycloaddition to an alkyne-bearing iron oxide templating peptide, CMms6, for USPIO biomineralization under mild conditions. The coiled-coil protein, dubbed Q, has been previously shown to form nanofibers and, upon small molecule binding, further assembles into mesofibers via encapsulation and aggregation. The resulting hybrid material is capable of doxorubicin encapsulation as well as sensitive -weighted MRI darkening for strong imaging capability that is uniquely derived from a coiled-coil protein. 

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