Article
Biochemistry & Molecular Biology
Yunfeng Yan, Fangtao Zhu, Huahui Su, Xiaomin Liu, Qidi Ren, Fangqian Huang, Wenbo Ye, Mengdan Zhao, Yunchun Zhao, Junpeng Zhao, Qi Shuai
Summary: This study constructed a library of 144 functional triblock polymers and discovered three effective carriers for siRNA delivery through high-throughput screening. In vitro evaluation showed that the siRNA-loaded nanoparticles fabricated with these polymers effectively silenced luciferase genes with low cytotoxicity. The chemical structure of the polymers significantly affected the physicochemical properties and in vitro delivery efficacy of the siRNA-loaded nanoparticles. In vivo experiments demonstrated that siRNA nanoparticles based on a specific polymer accumulated at tumor sites, suggesting the potential of this polymer in improving blood circulation and biodistribution of siRNA nanoparticles. This functional triblock polymer platform holds great potential in siRNA-based cancer therapies.
MACROMOLECULAR BIOSCIENCE
(2022)
Article
Engineering, Environmental
Xiu Han, Yan Lu, Haiping Wu, Xiaoxiang Guan, Xueping Ma, Yanan Chu, Bingjie Zou, Guohua Zhou
Summary: In this study, a prism oligonucleotide nanoparticle (pONP)-based delivery system was designed for the specific release of siRNA into telomerase-positive cancer cells. Both in vitro and in vivo tests confirmed the high precision and effectiveness of this nanoparticle cage in delivering siRNA. This delivery method shows great promise for targeted siRNA release into cancer cells.
CHEMICAL ENGINEERING JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Michael Gabel, Annkathrin Knauss, Dagmar Fischer, Markus F. Neurath, Benno Weigmann
Summary: The RNA interference mechanism may represent a breakthrough in the therapy of diseases caused by gene defects or requiring the inhibition of specific genes. The limitations of siRNA can be overcome by further developments in nanoparticulate drug delivery. Surface-modified siRNA nanoparticles hold promise for more efficient and safer targeting of specific tissues, but developing such delivery strategies remains a major challenge.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Zhaoran Wang, Linlin Song, Qing Liu, Run Tian, Yingxu Shang, Fengsong Liu, Shaoli Liu, Shuai Zhao, Zihong Han, Jiashu Sun, Qiao Jiang, Baoquan Ding
Summary: By utilizing the DNA origami technique, a DNA nanodevice was constructed with siRNA and doxorubicin incorporated, enabling the release of siRNA in response to intracellular glutathione in tumors. This innovative strategy combining RNA interference and chemotherapy showed potent antitumor activity and marked biocompatibility, representing a promising approach for precise drug design in cancer therapy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Pharmacology & Pharmacy
Hiroki Tanaka, Nae Takata, Yu Sakurai, Tokuyuki Yoshida, Takao Inoue, Shinya Tamagawa, Yuta Nakai, Kota Tange, Hiroki Yoshioka, Masatoshi Maeki, Manabu Tokeshi, Hidetaka Akita
Summary: This study investigated the optimal lipid composition of LNPs for the delivery of siRNA and ASO, finding that the optimal compositions for siRNA and ASO were different and differed from those reported for mRNA in previous studies. The key processes for successful delivery of mRNA, siRNA, and ASO were identified as extracellular stability, endosomal escape, and cellular uptake, respectively, indicating the importance of optimizing LNP lipid compositions based on the type of nucleic acids being delivered.
Article
Biochemistry & Molecular Biology
Mark D. Ashton, Patricia A. Cooper, Sofia Municoy, Martin F. Desimone, David Cheneler, Steven D. Shnyder, John G. Hardy
Summary: This article discusses the development of biomaterials capable of controlling the release of agrochemicals/biologics/drugs/fragrances. By using degradable electroactive polymers, controlled release of a clinically relevant drug was achieved and shown to have good cytocompatibility in vitro. These stimuli-responsive biomaterials have potential applications in the fields of technology and medicine.
Article
Engineering, Biomedical
Yu Xia, Guoyi Tang, Yi Chen, Changbing Wang, Min Guo, Tiantian Xu, Mingqi Zhao, Yongjian Zhou
Summary: RNA interference (RNAi) is a promising method for treating malignant tumors, and in this study, RGDfC-SeNPs were successfully synthesized as a tumor-targeted carrier for delivering siSox2 to HepG2 liver cancer cells. The results showed that RGDfC-Se@siSox2 effectively silenced Sox2, inhibited tumor cell proliferation, migration, and invasion, induced apoptosis through reactive oxygen species production and mitochondrial membrane potential disruption, and significantly inhibited tumor growth in mice bearing HepG2 tumors. These findings suggest that RGDfC-SeNPs could be a valuable gene carrier for specific gene-targeted therapy in HCC.
BIOACTIVE MATERIALS
(2021)
Review
Biochemistry & Molecular Biology
Chaoyang Guan, Xiaoli Zhu, Chang Feng
Summary: DNA, as a natural biological material, is increasingly being utilized for biomedical applications due to its biocompatibility, ease of synthesis, modifiability, and programmability. Advancements in DNA synthesis and modification technology have led to the development of smart-responsive DNA nanodevices that can intelligently respond to external stimuli, providing new solutions for targeted drug delivery and tumor treatment. Looking ahead, there are promising prospects for further advancements in this field.
Article
Chemistry, Multidisciplinary
Esther H. Roh, Thomas H. Epps, Millicent O. Sullivan
Summary: The article introduces a mathematical framework that can predict siRNA-mediated gene silencing with minimal experimental data and guide nanocarrier design. It reveals that siRNA dilution is a key determinant of gene silencing kinetics, and the experimental and predicted results align closely in vitro and in vivo settings.
Article
Polymer Science
Alessandra Monaco, Beatriz Dias Barbieri, Gokhan Yilmaz, Robin J. Shattock, C. Remzi Becer
Summary: Gene delivery is a powerful technique used in the treatment of diseases. Biodegradable polymers, such as poly(amido amine)s, are a cheaper and safer alternative to expensive virus-based gene vectors. In this study, poly(amido amine)s with different side chain lengths and glycopolymers were developed for gene delivery. Sugar decorated poly(amido amine)s showed better transfection activity compared to non-decorated ones. Overall, biodegradable poly(amido amine)s with different alcohols and sugars were synthesized to develop an optimal saRNA delivery system.
Review
Chemistry, Applied
Milad Ashrafizadeh, Masoud Delfi, Farid Hashemi, Amirhossein Zabolian, Hossein Saleki, Morteza Bagherian, Negar Azami, Mahdi Vasheghani Farahani, Seyed Omid Sharifzadeh, Soodeh Hamzehlou, Kiavash Hushmandi, Pooyan Makvandi, Ali Zarrabi, Michael R. Hamblin, Rajender S. Varma
Summary: Gene therapy using siRNA faces challenges, but chitosan nanoparticles as carriers show promise in overcoming siRNA issues and demonstrating potential in cancer therapy.
CARBOHYDRATE POLYMERS
(2021)
Article
Chemistry, Multidisciplinary
Sibei Lei, Yan Gao, Jingmei Li, Xiaohua Chen, Weilin Zhou, Jieping Wu, Pingchuan Ma, Ke Men, Xingmei Duan
Summary: This study developed a novel drug release system that can control the release of siRNA and mRNA, protect these nucleic acids from biodegradation, and activate the immune response to effectively inhibit tumor growth. This research provides a valuable tool for cancer gene therapy.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Chemistry, Physical
Riho Tanimoto, Mitsuhiro Ebara, Koichiro Uto
Summary: In this study, enzymatically degradable hydrogels with tunable mesh sizes and crosslinking points were designed to evaluate the effectiveness of network structure estimations. The results show that the retention and release of FITC-dextran can be controlled by tuning the mesh size and degradability of the hydrogel.
Article
Chemistry, Multidisciplinary
Constantin von Schirnding, Ioanna Giopanou, Adam Hermawan, Lisa Wehl, Giannoula Ntaliarda, Bernhard Illes, Stefan Datz, Franz Geisslinger, Karin Bartel, Ann-Katrin Sommer, Marina Lianou, Veronika Weiss, Johann Feckl, Angelika M. Vollmar, Christoph Brauchle, Georgios T. Stathopoulos, Ernst Wagner, Andreas Roidl, Thomas Bein, Hanna Engelke
Summary: The novel ternary colloidal nanoparticles exhibit highly selective toxicity in killing cancer cells without the need for toxic drugs. By locally applying these nanoparticles, the tumor size was successfully reduced with only slightly increased pleural thickening observed.
Article
Chemistry, Multidisciplinary
Haohao Yin, Liping Sun, Yinying Pu, Jifeng Yu, Wei Feng, Caihong Dong, Bangguo Zhou, Dou Du, Yan Zhang, Yu Chen, Huixiong Xu
Summary: This study identified the activation of NFE2L2 during SDT, which hindered the treatment efficacy. A novel HMME @ Lip-Cas9 system was designed to enhance therapeutic efficiency, laying the groundwork for new approaches in HCC management.
ACS CENTRAL SCIENCE
(2021)
Article
Nanoscience & Nanotechnology
Kelly R. Rhodes, Ariel Isser, John W. Hickey, Elana Ben-Akiva, Randall A. Meyer, Alyssa K. Kosmides, Natalie K. Livingston, Stephany Y. Tzeng, Jonathan P. Schneck, Jordan J. Green
Summary: Biomimetic biomaterials show promise in cancer immunotherapy by engaging the immune system to generate antitumor responses. By modulating the interface between biomaterial surfaces and target cells, enhanced biological functions can be achieved. Synthetic artificial antigen presenting cells have potential as a directly injectable acellular therapy in the future.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Chemistry, Multidisciplinary
Johan Karlsson, Stephany Y. Tzeng, Shayan Hemmati, Kathryn M. Luly, Olivia Choi, Yuan Rui, David R. Wilson, Kristen L. Kozielski, Alfredo Quinones-Hinojosa, Jordan J. Green
Summary: This study introduces a novel strategy involving photocrosslinking of bioreducible nanoparticles to enhance the systemic delivery of RNA. The photocrosslinked bioreducible nanoparticles exhibit improved stability and efficient siRNA-mediated gene silencing effects in melanoma tumors, providing potential for advancing nucleic acid-based therapeutics delivery technologies.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Oncology
Hannah J. Vaughan, Camila G. Zamboni, Nicholas P. Radant, Pranshu Bhardwaj, Esther Revai Lechtich, Laboni F. Hassan, Khalid Shah, Jordan J. Green
Summary: Researchers have developed poly(beta-amino ester) nanoparticles to locally deliver a secretable TRAIL protein to liver cancer cells, inducing apoptosis effectively. By combining NP treatment with histone deacetylase inhibitors, they achieved over 80% TRAIL-mediated cell death in target cancer cells. This approach offers a new potential strategy for cancer treatment by addressing multiple challenges associated with TRAIL therapy.
MOLECULAR THERAPY-ONCOLYTICS
(2021)
Review
Engineering, Biomedical
Erin W. Kavanagh, Jordan J. Green
Summary: Genetic medicine has the potential to efficiently treat various human diseases, but the main challenge lies in the delivery of the treatment. Nanoparticles, engineered to mimic the efficiency of viruses, have shown promise in terms of safety, flexibility, targeting, and manufacturing. Recent progress in clinical validation of nonviral gene transfer nanoparticles has been significant, with FDA approval for gene expression and silencing. Lipid nanoparticles have been the focus, but other nanomaterials with desirable attributes like biodegradability, scalability, and cell targeting are also being developed. This review discusses the current state of the field, challenges in delivery, and opportunities for engineered nanomaterials, including long-term therapeutic gene editing.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Multidisciplinary Sciences
Yuan Rui, David R. Wilson, Stephany Y. Tzeng, Hannah M. Yamagata, Deepti Sudhakar, Marranne Conge, Cynthia A. Berlinicke, Donald J. Zack, Anthony Tuesca, Jordan J. Green
Summary: Nanoparticle-based mRNA therapeutics show great promise, but cellular internalization and endosomal escape pose challenges for cytosolic delivery. Researchers developed a dual nanoparticle uptake and endosomal disruption assay, which can detect cellular internalization and endosomal disruption. The study found that this assay has higher predictive capacity for mRNA delivery compared to conventional polymer and nanoparticle characteristics.
Article
Materials Science, Multidisciplinary
Randall A. Meyer, Sarah Y. Neshat, Jordan J. Green, Jose Luis Santos, Anthony D. Tuesca
Summary: mRNA gene therapy has the potential to enable various therapeutic applications, but its successful clinical translation has been limited due to inadequate understanding of organ-specific protein expression. Studies have shown that carrier material properties and routes of administration are important factors in mRNA therapeutic expression profiles. Understanding trends in tissue-specific mRNA delivery materials can unlock the full potential of therapeutic mRNA medicines.
MATERIALS TODAY ADVANCES
(2022)
Article
Engineering, Biomedical
Dennis Gong, Elana Ben-Akiva, Arshdeep Singh, Hannah Yamagata, Savannah Est-Witte, Julie K. Shade, Natalia A. Trayanova, Jordan J. Green
Summary: Developing efficient non-viral gene delivery reagents for hard-to-transfect cell types remains challenging, often relying on brute force screening. High-throughput computational methods for evaluating biomaterials can expedite optimization by quickly exploring large chemical design spaces. In this study, machine learning algorithms were applied to a dataset of synthetic biodegradable polymers, enabling the prediction of transfection efficiency. Experimental validation confirmed the accuracy of computational predictions, highlighting the potential of computational screening in the development of gene delivery nanoparticles.
ACTA BIOMATERIALIA
(2022)
Article
Nanoscience & Nanotechnology
Kathryn M. Luly, Huilin Yang, Stephen J. Lee, Wentao Wang, Seth D. Ludwig, Haley E. Tarbox, David R. Wilson, Jordan J. Green, Jamie B. Spangler
Summary: The study compared the use of PBAEs with linear 25 kDa PEI for transient transfection, showing that PBAEs demonstrated superior transfection efficiency and enhanced protein production in both HEK and CHO cells, making them potentially attractive reagents for recombinant protein production.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2022)
Review
Nanoscience & Nanotechnology
Joanna Yang, Kathryn M. Luly, Jordan J. Green
Summary: Nonviral nanoparticles offer an attractive alternative to viral vectors for gene therapy, encapsulating or functionalizing nucleic acids to protect them. Adjusting physiochemical properties of the nanoparticles can improve cellular uptake and gene delivery. Overcoming extracellular barriers, such as the blood-brain barrier, in gene therapy for the central nervous system is challenging but possible.
WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Elana Ben-Akiva, Johan Karlsson, Shayan Hemmati, Hongzhe Yu, Stephany Y. Tzeng, Drew M. Pardoll, Jordan J. Green
Summary: Nanoparticle-based mRNA cancer vaccines show great promise for personalized cancer treatments. We developed a bioreducible lipophilic poly(beta-amino ester) nanocarrier that can efficiently deliver multiple antigen-encoding mRNAs and nucleic acid-based adjuvants to dendritic cells. The engineered nanocarrier facilitated targeted delivery without the need for surface functionalization and resulted in robust CD8+ T cell responses and efficient antitumor therapy in murine melanoma and colon adenocarcinoma models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Materials Science, Biomaterials
Sarah Y. Neshat, Stuart J. Bauer, Kelly R. Rhodes, Victor M. Quiroz, Valerie W. Wong, Shirley M. Lowmaster, Stephany Y. Tzeng, Jordan J. Green, Joshua C. Doloff
Summary: Type 1 diabetes (T1D) is a life-threatening condition that can be improved by islet transplantation, but the success can vary due to the patient's immune response. Artificial antigen-presenting cells (aAPCs) can promote immune acceptance and generate a tolerogenic response by inducing regulatory T cells (Tregs). The study investigated the properties of a specific type of aAPCs (TolAPCs) and their impact on the immune system in mice, showing potential for islet protection and glucose-stimulated insulin secretion. However, further improvements are needed for long-term efficacy and control of other immune cell responses.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
Article
Engineering, Biomedical
Sarah Y. Neshat, Chun Hei Ryan Chan, Jawaun Harris, Osamah M. Zmily, Savannah Est-Witte, Johan Karlsson, Sydney R. Shannon, Manav Jain, Joshua C. Doloff, Jordan J. Green, Stephany Y. Tzeng
Summary: Immuno-oncology therapies aim to induce sustained tumor regression, but current methods are in need of improvement. An antigen-free method of cancer immunotherapy that stimulates the immune system without knowledge of neoantigens has been developed, along with a local delivery system to minimize systemic toxicity. A gene delivery nanoparticle platform has been engineered to reprogram the tumor microenvironment and activate cytotoxic lymphocytes, resulting in tumor regression and clearance.
Article
Materials Science, Biomaterials
Kathryn M. Luly, Jordan J. Green, Joel C. Sunshine, Stephany Y. Tzeng
Summary: In this study, researchers used reprogramming nanoparticles (NPs) to deliver immunostimulatory genes and enhance immunotherapy for skin cancer. They found that these NPs can reprogram the tumor immune microenvironment, induce strong T-cell-driven immune responses, and slow tumor growth and improve survival rates in vivo.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
Review
Materials Science, Biomaterials
Sydney R. Shannon, Elana Ben-Akiva, Jordan J. Green
Summary: Gene therapies are revolutionizing the treatment of many human diseases, and it is important to consider both the delivery materials and cargos for maximum efficacy and safety. Non-viral delivery mechanisms and CRISPR technology have great potential in immune cell gene editing, but there are challenges that need to be overcome.
BIOMATERIALS SCIENCE
(2022)
Article
Multidisciplinary Sciences
Myungjun Ko, Monish R. Makena, Paula Schiapparelli, Paola Suarez-Meade, Allatah X. Mekile, Bachchu Lal, Hernando Lopez-Bertoni, Kristen L. Kozielski, Jordan J. Green, John Laterra, Alfredo Quinones-Hinojosa, Rajini Rao
Summary: Self-renewing stem cells play a crucial role in tumor initiation and therapeutic resistance in glioblastoma. The endosomal pH regulator NHE9 promotes cell surface expression and phosphorylation of multiple receptor tyrosine kinases (RTKs), leading to the activation of oncogenic signaling pathways and induction of pluripotency genes. Alkalization of the endosomal lumen through the use of chemical agents can bypass NHE9 and induce similar effects.
