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1. Nanomaterials for Protein Delivery in Anticancer Applications

   https://doi.org/10.3390/pharmaceutics13020155  

   Yau, Anne; Lee, Jinhyung; Chen, Yupeng (February 2021, Pharmaceutics)

   null (Ed.)

   Nanotechnology platforms, such as nanoparticles, liposomes, dendrimers, and micelles have been studied extensively for various drug deliveries, to treat or prevent diseases by modulating physiological or pathological processes. The delivery drug molecules range from traditional small molecules to recently developed biologics, such as proteins, peptides, and nucleic acids. Among them, proteins have shown a series of advantages and potential in various therapeutic applications, such as introducing therapeutic proteins due to genetic defects, or used as nanocarriers for anticancer agents to decelerate tumor growth or control metastasis. This review discusses the existing nanoparticle delivery systems, introducing design strategies, advantages of using each system, and possible limitations. Moreover, we will examine the intracellular delivery of different protein therapeutics, such as antibodies, antigens, and gene editing proteins into the host cells to achieve anticancer effects and cancer vaccines. Finally, we explore the current applications of protein delivery in anticancer treatments. 

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2. Peptides as key components in the design of non‐viral vectors for gene delivery

   https://doi.org/10.1002/pep2.24189  

   Thomas, Joseph; Punia, Kamia; Montclare, Jin Kim (September 2020, Peptide Science)

   Abstract Successful clinical implementation of gene delivery relies on the use of viral or non‐viral based vectors to package and protect the therapeutic nucleic acid. These vehicles must also be able to direct the fate of the cargo once it has entered the cell to ensure that the nucleic acid is functional, and the desired outcome is achieved. Compared to viral vectors, non‐viral vectors have the advantage of incorporating different material types such as lipids, polymers, and peptides to tune overall safety and efficacy. Peptides are especially powerful when used in gene delivery vectors as they are able to increase gene delivery efficacy by introducing new biochemical functionality. This review will discuss the use of peptides as central design components in non‐viral gene delivery vectors. The contribution of the peptide component to the overall functionality of the delivery vehicle will be highlighted, with a focus on peptides as the only vehicle component or peptides in complex assemblies with lipids or polymers. 

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3. Implantable optical fibers for immunotherapeutics delivery and tumor impedance measurement

   https://doi.org/10.1038/s41467-021-25391-z  

   Chin, Ai Lin; Jiang, Shan; Jang, Eungyo; Niu, Liqian; Li, Liwu; Jia, Xiaoting; Tong, Rong (December 2021, Nature Communications)

   null (Ed.)

   Abstract Immune checkpoint blockade antibodies have promising clinical applications but suffer from disadvantages such as severe toxicities and moderate patient–response rates. None of the current delivery strategies, including local administration aiming to avoid systemic toxicities, can sustainably supply drugs over the course of weeks; adjustment of drug dose, either to lower systemic toxicities or to augment therapeutic response, is not possible. Herein, we develop an implantable miniaturized device using electrode-embedded optical fibers with both local delivery and measurement capabilities over the course of a few weeks. The combination of local immune checkpoint blockade antibodies delivery via this device with photodynamic therapy elicits a sustained anti-tumor immunity in multiple tumor models. Our device uses tumor impedance measurement for timely presentation of treatment outcomes, and allows modifications to the delivered drugs and their concentrations, rendering this device potentially useful for on-demand delivery of potent immunotherapeutics without exacerbating toxicities. 

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4. Injectable nanofibrillar hydrogels based on charge-complementary peptide co-assemblies

   https://doi.org/10.1039/D0BM01372B  

   Soto Morales, Bethsymarie; Liu, Renjie; Olguin, Juanpablo; Ziegler, Abigail M.; Herrera, Stephanie M.; Backer-Kelley, Kimberly L.; Kelley, Karen L.; Hudalla, Gregory A. (April 2021, Biomaterials Science)

   null (Ed.)

   Injectable hydrogels are attractive for therapeutic delivery because they can be locally administered through minimally-invasive routes. Charge-complementary peptide nanofibers provide hydrogels that are suitable for encapsulation of biotherapeutics, such as cells and proteins, because they assemble under physiological temperature, pH, and ionic strength. However, relationships between the sequences of charge-complementary peptides and the physical properties of the hydrogels that they form are not well understood. Here we show that hydrogel viscoelasticity, pore size, and pore structure depend on the pairing of charge-complementary “CATCH(+/−)” peptides. Oscillatory rheology demonstrated that co-assemblies of CATCH(4+/4−), CATCH(4+/6−), CATCH(6+/4−), and CATCH(6+/6−) formed viscoelastic gels that can recover after high-shear and high-strain disruption, although the extent of recovery depends on the peptide pairing. Cryogenic scanning electron microscopy demonstrated that hydrogel pore size and pore wall also depend on peptide pairing, and that these properties change to different extents after injection. In contrast, no obvious correlation was observed between nanofiber charge state, measured with ζ-potential, and hydrogel physical properties. CATCH(4+/6−) hydrogels injected into the subcutaneous space elicited weak, transient inflammation whereas CATCH(6+/4−) hydrogels induced stronger inflammation. No antibodies were raised against the CATCH(4+) or CATCH(6−) peptides following multiple challenges in vehicle or when co-administered with an adjuvant. These results demonstrate that CATCH(+/−) peptides form biocompatible injectable hydrogels with viscoelastic properties that can be tuned by varying peptide sequence, establishing their potential as carriers for localized delivery of therapeutic cargoes. 

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5. Intracellular Antibody Delivery Mediated by Lipids, Polymers, and Inorganic Nanomaterials for Therapeutic Applications

   https://doi.org/10.1002/adtp.202000178  

   Li, Yamin; Li, Peixuan; Li, Raissa; Xu, Qiaobing (September 2020, Advanced Therapeutics)

   Abstract Therapeutic antibodies, due to their high affinity and specificity toward their biological targets, may demonstrate reduced harmful side effects compared with traditional drug moieties. While most of the as‐yet clinically approved antibody therapeutics have targeted extracellular or membrane‐bound domains, the ability to target intracellular antigens with antibodies opens up tremendous opportunities for imaging, diagnosis, and therapeutic applications. Generally, delivery concerns have limited the ability to target intracellular antigens, as many antibodies cannot easily cross the cell membrane due to their size and surface chemistry. Delivery platforms have been explored to address this issue, including physical methods, fusion protein/peptide techniques, and synthetic carrier‐based systems. This review summarizes the progress of carrier‐based intracellular antibody delivery systems employing synthetic lipids, polymers, and inorganic nanomaterials. Antibodies targeting various epitopes have been loaded through adsorption, conjugation, or physical encapsulation strategies. Successful intracellular deliveries have been demonstrated largely through fluorescence imaging using dye‐labeled antibody cargos. Specific synthetic delivery platforms have great potential for ex vivo and in vivo therapeutic applications. Challenges and opportunities are further discussed for material scientists to explore in this research area. 

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