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1. Doxorubicin‐Loaded Microrobots for Targeted Drug Delivery and Anticancer Therapy

   https://doi.org/10.1002/adhm.202300939  

   Mallick, Sudipta; Abouomar, Ramadan; Rivas, David; Sokolich, Max; Kirmizitas, Fatma Ceren; Dutta, Aditya; Das, Sambeeta (June 2023, Advanced Healthcare Materials)

   Abstract Micro‐sized magnetic particles (also known as microrobots [MRs]) have recently been shown to have potential applications for numerous biomedical applications like drug delivery, microengineering, and single cell manipulation. Interdisciplinary studies have demonstrated the ability of these tiny particles to actuate under the action of a controlled magnetic field that not only drive MRs in a desired trajectory but also precisely deliver therapeutic payload to the target site. Additionally, optimal concentrations of therapeutic molecules can also be delivered to the desired site which is cost‐effective and safe especially in scenarios where drug dose‐related side effects are a concern. In this study, MRs are used to deliver anticancer drugs (doxorubicin) to cancer cells and subsequent cell death is evaluated in different cell lines (liver, prostate, and ovarian cancer cells). Cytocompatibility studies show that MRs are well‐tolerated and internalized by cancer cells. Doxorubicin (DOX) is chemically conjugated with MRs (DOX‐MRs) and magnetically steered toward cancer cells using the magnetic controller. Time‐lapsed video shows that cells shrink and eventually die when MRs are internalized by cells. Taken together, this study confirms that microrobots are promising couriers for targeted delivery of therapeutic biomolecules for cancer therapy and other non‐invasive procedures that require precise control. 

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2. 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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3. Nano-Inspired Technologies for Peptide Delivery

   https://doi.org/10.2174/1389203720666191202112429  

   Covarrubias-Zambrano, Obdulia; Yu, Jing; Bossmann, Stefan H. (April 2020, Current Protein & Peptide Science)

   null (Ed.)

   Nano-inspired technologies offer unique opportunities to treat numerous diseases by using therapeutic peptides. Therapeutic peptides have attractive pharmacological profiles and can be manufactured at relatively low costs. The major advantages of using a nanodelivery approach comprises significantly lower required dosages compared to systemic delivery, and thus reduced toxicity and immunogenicity. The combination of therapeutic peptides with delivery peptides and nanoparticles or small molecule drugs offers systemic treatment approaches, instead of aiming for single biological targets or pathways. This review article discusses exemplary state-of-the-art nanosized delivery systems for therapeutic peptides and antibodies, as well as their biochemical and biophysical foundations and emphasizes still remaining challenges. The competition between using different nanoplatforms, such as liposome-, hydrogel-, polymer-, silica nanosphere-, or nanosponge-based delivery systems is still “on” and no clear frontrunner has emerged to date. 

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4. Efficacy and clinical monitoring strategies for immune checkpoint inhibitors and targeted cytokine immunotherapy for locally advanced and metastatic colorectal cancer

   https://doi.org/https://doi.org/10.1016/j.cytogfr.2019.10.002  

   Bess, S; Greening, G; Muldoon, T (October 2019, Cytokine growth factor reviews)

   Colorectal cancer (CRC) is the fourth most common cancer type and is the second leading cause of cancer deaths annually in the United States. Conventional treatment options include postoperative (adjuvant) and preoperative (neoadjuvant) chemotherapy and radiotherapy. Although these treatment modalities have shown to decrease tumor burden, a major limitation to chemothearpy/radiotherapy is the high recurrence rate in patients. Immune-modulation strategies have emerged as a promising new therapeutic avenue to reduce this recurrence rate while minimizing undesirable systemic side effects. This review will focus specifically on the mechanisms of monoclonal antibodies: immune checkpoint inhibitors and cytokines, as well as current drugs approved by the Food and Drug Administration (FDA) and new clinical/pre-clinical trials. Finally, this review will investigate emerging methods used to monitor tumor response post-treatment. 

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5. Use of photoimmunoconjugates to characterize ABCB1 in cancer cells

   https://doi.org/10.1515/nanoph-2021-0252  

   Liang, Barry J.; Lusvarghi, Sabrina; Ambudkar, Suresh V.; Huang, Huang-Chiao (July 2021, Nanophotonics)

   null (Ed.)

   Abstract Accurate detection of ATP-binding cassette drug transporter ABCB1 expression is imperative for precise identification of drug-resistant tumors. Existing detection methods fail to provide the necessary molecular details regarding the functional state of the transporter. Photoimmunoconjugates are a unique class of antibody–dye conjugates for molecular diagnosis and therapeutic treatment. However, conjugating hydrophobic photosensitizers to hydrophilic antibodies is quite challenging. Here, we devise a photoimmunoconjugate that combines a clinically approved benzoporphyrin derivative (BPD) photosensitizer and the conformational-sensitive UIC2 monoclonal antibody to target functionally active human ABCB1 (i.e., ABCB1 in the inward-open conformation). We show that PEGylation of UIC2 enhances the BPD conjugation efficiency and reduces the amount of non-covalently conjugated BPD molecules by 17%. Size exclusion chromatography effectively separates the different molecular weight species found in the UIC2–BPD sample. The binding of UIC2–BPD to ABCB1 was demonstrated in lipidic nanodiscs and ABCB1-overexpressing triple negative breast cancer (TNBC) cells. UIC2–BPD was found to retain the conformation sensitivity of UIC2, as the addition of ABCB1 modulators increases the antibody reactivity in vitro . Thus, the inherent fluorescence capability of BPD can be used to label ABCB1-overexpressing TNBC cells using UIC2–BPD. Our findings provide insight into conjugation of hydrophobic photosensitizers to conformation-sensitive antibodies to target proteins expressed on the surface of cancer cells. 

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