Article
Chemistry, Multidisciplinary
Yu Sakurai, Nodoka Abe, Keito Yoshikawa, Ryotaro Oyama, Satoshi Ogasawara, Takeshi Murata, Yuta Nakai, Kota Tange, Hiroki Tanaka, Hidetaka Akita
Summary: This study developed a method for selective delivery of siRNA to LECs using LNPs. The method of modifying LNPs used in the study shows promise for expanding the delivery of nucleic acids in the future.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Johanna Voigt, Christoph Meyer, Frank Bordusa
Summary: Bispecific antibodies (bsAbs) are emerging as a leading class of immunotherapies for cancer treatment. This study presents novel chemo-enzymatic and purely enzymatic strategies for generating bispecific antibody fragments, which show promising results in breast cancer cell lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Biomedical
Xiaokang Wang, Xichao Zhou, Huan Zhao, Xu Chen, Yu Zhang, Miao Wang, Huilin Yang, Guoqing Pan, Qin Shi
Summary: This study presents an upgraded mussel-inspired strategy for surface bioengineering of osteoimplants by combining mussel adhesion and bioorthogonal click chemistry. The approach involves a synthetic peptide containing DOPA units and DBCO terminal for stable adhesion and subsequent conjugation with biomolecules. The strategy was shown to be effective in modifying surfaces of diverse orthopaedic materials to meet essential requirements of osteoimplants. The molecular specificity of bioorthogonal conjugation and the universality of mussel adhesion mechanism together provide a versatile surface bioengineering method for a wider range of biomedical implants.
BIOMEDICAL MATERIALS
(2021)
Article
Chemistry, Organic
Karel Thooft, Wander Van Breedam, Francis Santens, Elise Wyseure, Sandrine Vanmarcke, Simon Devos, Nico Callewaert, Annemieke Madder
Summary: The recent development of the GlyConnect-oxime (GC) protein conjugation strategy provides a new approach for site-selective glycan-based conjugation. Exploration of multicomponent reactions (MCR) for protein conjugation holds the potential of introducing multiple functional groups in a single reaction step.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Biophysics
Changkyu Lee
Summary: Click chemistry was used to synthesize GOD-BSA nanoparticles that can efficiently and rapidly conjugate proteins. These nanoparticles are non-toxic, biodegradable, and exhibit better anticancer activity when compared to GOD alone. They may serve as a promising drug delivery system for protein enzymes.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Article
Chemistry, Analytical
Mutsuo Nuriya, Yosuke Ashikari, Takanori Iino, Takuya Asai, Jingwen Shou, Keiko Karasawa, Kaho Nakamura, Yasuyuki Ozeki, Yukari Fujimoto, Masato Yasui
Summary: The development of alkyne-tagged dopamine compounds (ATDAs) provides a minimally invasive and uniquely identifiable tool to mimic dopamine in neurons and brain tissues, allowing for detailed characterization of dopamine dynamics. This approach can potentially be applied to other small-sized neurotransmitters as well, facilitating research on their dynamics in the brain.
ANALYTICAL CHEMISTRY
(2021)
Article
Polymer Science
Henrik-Alexander Christ, Yannick Bourgat, Henning Menzel
Summary: The optimization of polysaccharide chitosan conjugation with functional carboxylic acids using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and hydroxy benzotriazole was demonstrated, showing resource-efficient synthesis of highly functionalized chitosan with optimal parameters. Catalytic amounts of hydroxy benzotriazole and tight pH control in the reaction mixture led to efficient incorporation of desired moieties as side chains in chitosan. Results showed high degree of substitution and coupling efficacy for various carboxylic acids, indicating broad applicability for chitosan functionalization.
Article
Chemistry, Multidisciplinary
Haipei Liu, Zhaowei Liu, Mariana Sa Santos, Michael A. A. Nash
Summary: Single-molecule force spectroscopy (SMFS) is a powerful tool for studying protein folding and mechanical properties. However, the traditional method of immobilization using lysine residues results in a heterogeneous distribution of tether positions. In this study, we compared lysine-based immobilization to site-specific immobilization using genetically encoded peptide tags (ybbR). Our results showed that lysine-based immobilization led to signal deterioration and incorrect classification of unfolding pathways. We also developed a mixed immobilization approach that partially recovered specific signals.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Bin Liu, Khushboo Singh, Shuai Gong, Mine Canakci, Barbara A. Osborne, S. Thayumanavan
Summary: Protein-antibody conjugates (PACs) offer a promising approach for targeted delivery of protein therapeutics to specific cells by combining the advantages of biologics and antibody-drug conjugates. Utilizing spherical polymer brushes and orthogonal click chemistries, PACs can specifically target cells based on the presence of target antigen on the cell surface. The adaptability of PACs opens up new opportunities for targeted biologics in therapeutics and sensing.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Yanbo Zhao, Vijay Chudasama, James R. Baker
Summary: We synthesized and applied trifunctional reagents to modify the native, solvent accessible disulfide bonds in trastuzumab using dual-modality approach. The reagents were developed from the dibromomaleimide (DBM) platform with two orthogonal clickable functional groups built around a lysine core. We also developed an aryl diselenide additive that enables rapid reduction of antibody disulfide bonds in 4 minutes and a rapid overall reduction-bridging-double click sequence.
Review
Medicine, Research & Experimental
Omozojie P. Aigbogun, Christopher P. Phenix, Ed S. Krol, Eric W. Price
Summary: Small-molecule drugs have short in vivo half-lives, hindering their success as therapeutics. Chemically programmed antibodies (cPAbs) have been developed to address these limitations by augmenting small molecules with antibodies for effector functions and prolonged pharmacokinetic profiles. This review summarizes the different methods used to produce cPAbs and highlights their potential applications in antibody modification fields.
MOLECULAR PHARMACEUTICS
(2023)
Article
Agriculture, Multidisciplinary
Luyu Wei, Zhilong Wang, Yiping Chen
Summary: Researchers have developed an optical biosensor for highly sensitive and facile detection of ochratoxin A (OTA). The biosensor utilizes an enzyme-mediated click reaction for signal amplification and polystyrene nanoparticles (PNPs) for signal readout. The biosensor demonstrates improved sensitivity and simplified procedures, making it a promising tool for mycotoxin screening.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Jia-Qi Zhu, Han Wu, Zhen-Li Li, Xin-Fei Xu, Hao Xing, Ming-Da Wang, Hang-Dong Jia, Lei Liang, Chao Li, Li-Yang Sun, Yu-Guang Wang, Feng Shen, Dong-Sheng Huang, Tian Yang
Summary: This article summarizes the synthesis methods and applications of nanocomposite responsive hydrogels, which can respond to external or internal physiological stimuli and be used for responsive drug delivery.
ADVANCED MATERIALS
(2022)
Article
Polymer Science
Mustafa Ersin Pekdemir, Abdulrahman Tukur, Mehmet Coskun
Summary: In this study, a copolymer with magnetic nanoparticles was successfully synthesized through modification and copolymerization, which was then bonded to PVC to enhance its thermal stability and achieve saturation magnetization. The dielectric properties of the copolymer varied with frequency, with an increase in AC conductivity.
Article
Engineering, Environmental
Oanh-Vu Pham-Nguyen, Wei Mao, Hoai-Thuong Duc Bui, Wanho Cho, Song Rae Kim, Hyuk Sang Yoo
Summary: Size-dependent localization of nanoscale carriers is crucial for improving anticancer therapy by enhancing therapeutic windows and minimizing side effects. In this study, polymeric nanoparticle clusters were prepared to achieve diagnostic and therapeutic systems with a single nanocluster that could be clicked in response to the surrounding enzyme levels in tumor tissues. The results showed that these nanoparticle clusters have potential as tools for monitoring tumor progression and therapeutic efficacy.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Lu Peng, Benabdallah Nadia, Jiang Wen, Brian W. Simons, Zhang Hanwen, Robert F. Hobbs, Ulmert David, Brian C. Baumann, Russell K. Pachynski, Abhinav K. Jha, Daniel L. J. Thorek
Summary: Digital autoradiography (DAR) is a powerful tool for analyzing the distribution of radiopharmaceuticals in tissue sections. However, it has limitations such as low image resolution and high background noise. To address these issues, researchers have developed a content-adaptive restoration algorithm (PG-PEM) that can improve resolution, contrast, and the distribution of radiopharmaceuticals in DAR imaging.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Biochemical Research Methods
Linghan Mei, Fabiana Zappala, Andrew Tsourkas
Summary: Bispecific antibodies are capable of binding two antigens simultaneously, leading to unique biological effects. Two methods are introduced for rapid assembly of Bispecific antibodies from any two off-the-shelf IgG antibodies, allowing for low-cost, high-throughput production and validation.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Joshua J. Woods, Ryan Unnerstall, Abbie Hasson, Diane S. Abou, Valery Radchenko, Daniel L. J. Thorek, Justin J. Wilson
Summary: This study investigated four equatorial-spanning ligands as uranium chelators. The results showed that the complexes formed by these ligands with UO22+ were highly stable and exhibited good stability in vivo. The hox ligand demonstrated higher thermodynamic stability, likely due to its lower strain energy. The ligands remained >95% stable in human plasma and >80% intact in the presence of hydroxyapatite (HAP). In vivo experiments in mice showed that the uranium complexes of these ligands did not accumulate in the skeletal system. Overall, these equatorial-spanning ligands hold great promise for 230U TAT.
INORGANIC CHEMISTRY
(2022)
Article
Engineering, Biomedical
Tao Gui, Lijun Luo, Bonirath Chhay, Leilei Zhong, Yulong Wei, Lutian Yao, Wei Yu, Jun Li, Charles L. Nelson, Andrew Tsourkas, Ling Qin, Zhiliang Cheng
Summary: Oxidative stress and reactive oxygen species play important roles in the development and progression of osteoarthritis (OA). This study utilized SOD-loaded nanoparticles to deliver antioxidant enzymes to mouse knee joints, demonstrating the accumulation of nanoparticles in the synovium and reduction of oxidative damage. Intra-articular injections of the nanoparticles were effective in attenuating OA initiation and progression, via reduction of reactive oxygen species production and catabolic protease synthesis.
Article
Medicine, Research & Experimental
Alexander Chan, Hejia Henry Wang, Rebecca M. Haley, Cindy Song, David Gonzalez-Martinez, Lukasz Bugaj, Michael J. Mitchell, Andrew Tsourkas
Summary: This study demonstrates the feasibility of using small protein scaffolds with anionic polypeptides to interact with positively charged nonviral lipid-based delivery systems, enabling efficient intracellular delivery. This method can be used to inhibit intracellular proteins that are currently not amenable to small molecule drugs and biologics.
MOLECULAR PHARMACEUTICS
(2022)
Article
Multidisciplinary Sciences
Fabiana Zappala, Elizabeth Higbee-Dempsey, Bian Jang, Joann Miller, Lesan Yan, Nicholas G. Minutolo, Gabriela T. Rosado Gonzalez, Andrew Tsourkas, Burcin Altun Ozdemir
Summary: Researchers have developed a simple method to attach a T cell-redirecting domain to off-the-shelf human immunoglobulin G (IgG) or native IgG, allowing the generation of T cell-redirecting autoantibodies (TRAAbs) without the need for antibody engineering, cloning, or knowledge of the antibody sequence. These TRAAbs preferentially bind tumor tissue over healthy tissue, indicating a previously unexplored therapeutic window. This approach represents a new paradigm in personalized medicine.
Article
Oncology
Diane S. Abou, Patrick Zerkel, James Robben, Mark McLaughlin, Tim Hazlehurst, David Morse, Thaddeus J. Wadas, Darpan N. Pandya, Reiko Oyama, Gregory Gaehle, Michael L. Nickels, Daniel L. J. Thorek
Summary: The study investigated the impact of Ac-225/Ac-227 material in radiolabeling and quality control evaluation, showing that peptides produced using generator produced Ac-225 can be radiolabeled efficiently. There were subtle but detectable differences in material produced using Ac-225/Ac-227.
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
(2022)
Article
Oncology
Abbie Hasson, Wen Jiang, Nadia Benabdallah, Peng Lu, Mark S. Longtine, Bradley J. Beattie, Lucy Summer, Hanwen Zhang, Richard L. Wahl, Diane S. Abou, Daniel L. J. Thorek
Summary: This study demonstrates novel methods to characterize Th-227 and Ra-223 and verifies their feasibility through purity evaluation of a Th-227-labeled protein construct. The results show that the gamma counter and alpha camera can rapidly and quantitatively distinguish the radionuclidic purity of Th-227 and Ra-223, while the radio-TLC has limited ability in describing purity.
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
(2023)
Article
Endocrinology & Metabolism
Tao Gui, Yulong Wei, Lijun Luo, Jun Li, Leilei Zhong, Lutian Yao, Frank Beier, Charles L. Nelson, Andrew Tsourkas, X. Sherry Liu, Motomi Enomoto-Iwamoto, Feifan Yu, Zhiliang Cheng, Ling Qin
Summary: This study demonstrates the importance of EGFR signaling in maintaining articular cartilage during PTOA development and explores the development of novel nanomedicines for PTOA treatment.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Kyuhwan Shim, Mark S. Longtine, Diane S. Abou, Mark J. Hoegger, Richard S. Laforest, Daniel L. J. Thorek, Richard L. Wahl
Summary: In this study, the third-generation human anti-CD20 antibody ofatumumab was labeled with Lu-177 and showed favorable in vitro characteristics and therapeutic efficacy in a murine model of disseminated NHL. The results indicate that [Lu-177]Lu-ofatumumab has potential for clinical translation to treat NHL.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Article
Oncology
Claire M. Storey, Mohamed Altai, Mesude Bicak, Darren R. Veach, Katharina Lueckerath, Gabriel Adrian, Michael R. McDevitt, Teja Kalidindi, Julie E. Park, Ken Herrmann, Diane Abou, Wahed Zedan, Norbert Peekhaus, Robert J. Klein, Robert Damoiseaux, Steven M. Larson, Hans Lilja, Daniel Thorek, David Ulmert
Summary: Noninvasive biomarkers for androgen receptor (AR) pathway activation are urgently needed to better monitor patient response to prostate cancer therapies. A novel PET modality targeting hK2 was found to accurately assess EBRT-induced AR activity, which can be used for monitoring treatment response and development of resistance.
MOLECULAR CANCER RESEARCH
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Zekun Li, Nadia Benabdallah, Diane S. Abou, Brian C. Baumann, Farrokh Dehdashti, David H. Ballard, Jonathan Liu, Uday Jammalamadaka, Richard L. Laforest, Richard L. Wahl, Daniel L. J. Thorek, Abhinav K. Jha
Summary: Single-photon emission-computed tomography (SPECT) is challenging for estimating regional isotope uptake in alpha-particle-emitting radiopharmaceutical therapies (alpha-RPTs) due to complex emission spectra, low detected counts, stray-radiation-related noise, and image-degrading processes. To address this, a low-count quantitative SPECT (LC-QSPECT) method was developed, which directly estimates activity uptake from projection data, compensates for noise, and considers radioisotope and SPECT physics. The LC-QSPECT method outperformed traditional reconstruction and post-reconstruction compensation methods, providing reliable quantification for alpha-RPT SPECT.
IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES
(2023)
Article
Nanoscience & Nanotechnology
Rebecca M. Haley, Alexander Chan, Margaret M. Billingsley, Ningqiang Gong, Marshall S. Padilla, Emily H. Kim, Hejia Wang, Dingzi Yin, Kirk J. Wangensteen, Andrew Tsourkas, Michael J. Mitchell
Summary: This study demonstrates the successful delivery of DARPin protein K27-D30 to the cytosol of liver cancer cells using a lipid nanoparticle platform, inhibiting RAS-driven tumor growth and highlighting the potential of K27 as a new cancer therapeutic.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Nadia Benabdallah, Hanwen Zhang, Ryan Unnerstall, Amanda Fears, Lucy Summer, Michael Fassbender, Buck E. E. Rodgers, Diane Abou, Valery Radchenko, Daniel L. J. Thorek
Summary: A novel clinical-scale Ti-44/Sc-44 generator was built and evaluated in this study. Pharmacokinetic profiles of (ScCl3)-Sc-44, [Sc-44]-citrate, and [Sc-44]-NODAGA were explored, and the radiation burden of (ScCl3)-Sc-44 in humans was estimated.
Article
Nanoscience & Nanotechnology
Ahmad Amirshaghaghi, Wen-Chi Chang, Bonirath Chhay, Ariane R. Bartolomeu, Margie L. Clapper, Zhiliang Cheng, Andrew Tsourkas
Summary: The current standard of care for colon cancer surveillance, white light endoscopy, often misses dysplastic lesions that are not visible to the naked eye. Dye-based chromoendoscopy shows promise but lacks accuracy in differentiating tumor tissues from healthy tissues. This study aimed to improve tumor tissue visualization using various phthalocyanine (PC) dye-loaded micelles administered intravenously. Zinc PC (tetra-tert-butyl)-loaded micelles were identified as the optimal formulation, turning tumors dark blue for easy identification. These micelles were also effective in turning colorectal adenomas in mice a dark blue color, aiding in their detection and removal.
ACS APPLIED MATERIALS & INTERFACES
(2023)