PLGA-PEG-amine from PolySciTech used in development of nanoparticles for brain-tissue penetration

 

Delivery of medicinal molecules into the brain is difficult due to the blood-brain-barrier. Researchers at University of Technology Sydney and The University of Adelaide used PLGA-PEG-NH2 (AI058) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles enveloped in a protein corona. They used these particles to investigate mechanisms of uptake and delivery in brain tissue. This research holds promise to provide for improved therapies against brain diseases such as cancer and Alzheimer’s. Read more: Morshed, Nabila, Claire Rennie, Wei Deng, Lyndsey Collins-Praino, and Andrew Care. "Serum-derived protein coronas affect nanoparticle interactions with brain cells." Nanotechnology 35, no. 49 (2024): 495101. https://new.iopscience.iop.org/article/10.1088/1361-6528/ad7b40

“Neuronanomedicine is an emerging field bridging the gap between neuromedicine and novel nanotherapeutics. Despite promise, clinical translation of neuronanomedicine remains elusive, possibly due to a dearth of information regarding the effect of the protein corona on these neuronanomedicines. The protein corona, a layer of proteins adsorbed to nanoparticles following exposure to biological fluids, ultimately determines the fate of nanoparticles in biological systems, dictating nanoparticle–cell interactions. To date, few studies have investigated the effect of the protein corona on interactions with brain-derived cells, an important consideration for the development of neuronanomedicines. Here, two polymeric nanoparticles, poly(lactic-co-glycolic acid) (PLGA) and PLGA-polyethylene glycol (PLGA-PEG), were used to obtain serum-derived protein coronas. Protein corona characterization and liquid chromatography mass spectrometry analysis revealed distinct differences in biophysical properties and protein composition. PLGA protein coronas contained high abundance of globins (60%) and apolipoproteins (21%), while PLGA-PEG protein coronas contained fewer globins (42%) and high abundance of protease inhibitors (28%). Corona coated PLGA nanoparticles were readily internalized into microglia and neuronal cells, but not into astrocytes. Internalization of nanoparticles was associated with pro-inflammatory cytokine release and decreased neuronal cell viability, however, viability was rescued in cells treated with corona coated nanoparticles. These results showcase the importance of the protein corona in mediating nanoparticle–cell interactions.”

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PLGA from PolySciTech used in development of nanoparticles for treatment of atherosclerosis

 

Atherosclerosis (heart-disease) is due to formation of lipid-laden plaques in the arteries. These plaques typically express immunosuppressive signals which prevents their removal by immune system. Recently, researchers at University of Ottawa utilized PLGA (AP023) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles to deliver immunotargeting compounds to plaques. This research holds promise as a potential treatment for heart disease. Read more: Patel, Yukta, Shireesha Manturthi, Saras Tiwari, Esha Gahunia, Amandine Courtemanche, Michelle Gandelman, Marceline Côté, and Suresh Gadde. "Development of Pro-resolving and Pro-efferocytic Nanoparticles for Atherosclerosis Therapy." ACS Pharmacology & Translational Science (2024). https://pubs.acs.org/doi/abs/10.1021/acsptsci.4c00292

“Atherosclerosis is a major contributor to cardiovascular diseases with a high global prevalence. It is characterized by the formation of lipid-laden plaques in the arteries, which eventually lead to plaque rupture and thrombosis. While the current lipid-lowering therapies are generally effective in lowering the risk of cardiovascular events, they do not address the underlying causes of disease. Defective resolution of inflammation and impaired efferocytosis are the main driving forces of atherosclerosis. Macrophages recognize cells for clearance by the expression of “eat me” and “do not eat me” signals, including the CD47-SIRPα axis. However, the “do not eat me” signal CD47 is overexpressed in atherosclerotic plaques, leading to compromised efferocytosis and secondary necrosis. In this context, prophagocytic antibodies have been explored to stimulate the clearance of apoptotic cells, but they are nonspecific and impact healthy tissues. In macrophages, downstream of signal regulatory protein α, lie protein tyrosine phosphatases, SHP 1/2, which can serve as effective targets for selectively phagocytosing apoptotic cells. While increasing the efferocytosis targets the end stages of lesion development, the underlying issue of inflammation still persists. Simultaneously increasing efferocytosis and reducing inflammation can be effective therapeutic strategies for managing atherosclerosis. For instance, IL-10 is a key anti-inflammatory mediator that enhances efferocytosis via phosphoSTAT3 (pSTAT3) activation. In this study, we developed a combination nanotherapy by encapsulating an SHP-1 inhibitor (NSC 87877) and IL-10 in a single nanoparticle platform [(S + IL)-NPs] to enhance efferocytosis and inflammation resolution. Our studies suggest that (S + IL)-NPs successfully encapsulated both agents, entered the macrophages, and delivered the agents into intracellular compartments. Additionally, (S + IL)-NPs decreased inflammation by suppressing pro-inflammatory markers and enhancing anti-inflammatory mediators. They also exhibited the potential for improved phagocytic activity via pSTAT3 activation. Our nanomedicine-mediated upregulation of the anti-inflammatory and efferocytic responses in macrophages shows promise for the treatment of atherosclerosis.”

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PLGA-PEG-Mal from PolySciTech used in development of nano-delivery system for glioblastoma treatment

 

Glioblastoma is an aggressive brain cancer that is difficult to treat. Researchers at Southern University of Science and Technology, University of Texas Southwestern Medical Center, Xuzhou Medical University used PLGA-PEG-Maleimide (AI110) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles for targeting glioblastoma. They utilized this as part of a multifunctional system to maximize both radiotherapy and also immunotherapy against glioblastoma. Read more: Wen, Xin, Zhiying Shao, Xueting Chen, Hongmei Liu, Hui Qiu, Xin Ding, Debao Qu, Hui Wang, Andrew Z. Wang, and Longzhen Zhang. "A multifunctional targeted nano-delivery system with radiosensitization and immune activation in glioblastoma." Radiation Oncology 19, no. 1 (2024): 1-20. https://ro-journal.biomedcentral.com/articles/10.1186/s13014-024-02511-9

“Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation. The hypothesis of our study posits that instead of directly applying high doses of radiation, which is risky, a strategy could be developed to harness the immune-stimulating benefits of high-dose irradiation indirectly. This involves using nanoparticles to enhance antigen presentation and immune responses in a safer manner. Angiopep-2 (A2) was proved a satisfactory BBB and brain targeting and Dbait is a small molecule that hijack DNA double strand break damage (DSB) repair proteins to make cancer cells more sensitive to radiation. In view of that, the following two nanoparticles were designed to combine immunity of GBM, radiation resistance and BBB innovatively. One is cationic liposome nanoparticle interacting with Dbait (A2-CL/Dbait NPs) for radiosensitization effect; the other is PLGA-PEG-Mal nanoparticle conjugated with OX40 antibody (A2-PLGA-PEG-Mal/anti-OX40 NPs) for tumor-derived protein antigens capture and optimistic immunoregulatory effect of anti-OX40 (which is known to enhance the activation and proliferation T cells). Both types of nanoparticles showed favorable targeting and low toxicity in experimental models. Specifically, the combination of A2-CL/Dbait NPs and A2-PLGA-PEG-Mal/anti-OX40 NPs led to a significant extension in the survival time and a significant tumor shrinkage of mice with GBM. The study demonstrates that combining these innovative nanoparticles with conventional radiotherapy can effectively address key challenges in GBM treatment. It represents a significant step toward more effective and safer therapeutic options for GBM patients.”

PLGA-PEG-Mal (Cat# AI110): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AI110#h

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PLGA-PEG-PLGA Thermogels from PolySciTech used in development of controlled antibody release system

 

Thermogels have the ability to dissolve in cold water and form solid, gel structures when heated to body temperature. This allows them to deliver delicate molecules, like antibodies, which typically break down under normal processing conditions to form microparticles. Researchers at the Polish Academy of Sciences used PLGA-PEG-PLGA (AK012, AK024, AK088, AK091) and PLCL-PEG-PLCL (AK108) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a gel to deliver antibodies. This research holds promise to provide for improved biotherapy techniques in the future. Read more: Lipowska-Kur, Daria, Łukasz Otulakowski, Urszula Szeluga, Katarzyna Jelonek, and Alicja Utrata-Wesołek. "Diverse Strategies to Develop Poly (ethylene glycol)–Polyester Thermogels for Modulating the Release of Antibodies." Materials 17, no. 18 (2024): 4472. https://www.mdpi.com/1996-1944/17/18/4472

“Abstract: In this work, we present basic research on developing thermogel carriers containing high amounts of model antibody immunoglobulin G (IgG) with potential use as injectable molecules. The quantities of IgG loaded into the gel were varied to evaluate the possibility of tuning the dose release. The gel materials were based on blends of thermoresponsive and degradable ABA-type block copolymers composed of poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA–PEG–PLGA) or poly(lactide-co-caprolactone)-b-poly(ethylene glycol)-b-(lactide-co-caprolactone) (PLCL–PEG–PLCL). Primarily, the gels with various amounts of IgG were obtained via thermogelation, where the only factor inducing gel formation was the change in temperature. Next, to control the gels’ mechanical properties, degradation rate, and the extent of antibody release, we have tested two approaches. The first one involved the synergistic physical and chemical crosslinking of the copolymers. To achieve this, the hydroxyl groups located at the ends of the PLGA–PEG–PLGA chain were modified into acrylate groups. In this case, the thermogelation was accompanied by chemical crosslinking through the Michael addition reaction. Such an approach increased the dynamic mechanical properties of the gels and simultaneously prolonged their decomposition time. An alternative solution was to suspend crosslinked PEG–polyester nanoparticles loaded with IgG in a PLGA–PEG–PLGA gelling copolymer. We observed that loading IgG into thermogels lowered the gelation temperature (TGEL) value and increased the storage modulus of the gels, as compared with gels without IgG. The prepared gel materials were able to release the IgG from 8 up to 80 days, depending on the gel formulation and on the amount of loaded IgG. The results revealed that additional, chemical crosslinking of the thermogels and also suspension of particles in the polymer matrix substantially extended the duration of IgG release. With proper matching of the gel composition, environmental conditions, and the type and amount of active substances, antibody-containing thermogels can serve as effective IgG delivery materials. Keywords: thermogels; sol-gel transition; tandem gelation; polymer degradation; nanoparticles; antibody”

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PLCL-PEG-PLCL from PolySciTech used in exploration of tumor cytokine interactions

 

Despite years of research, the biological and cellular mechanisms of cancer are not fully understood. Understanding the complex biological pathways and cascades involved in cancer growth and, notably, immunosuppression can unlock potential targets for cancer-specific therapies. Researchers at Johns Hopkins University, Stanford University, University of Ulsan, used PLCL-PEG-PLCL (AK109) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a gel for delivery of METRNL cytokine as a means to explore the interaction of this cytokine with tumor cells. This research holds promise to improve immunotherapy approaches in the future. Read more: Jackson, Christopher M., Ayush Pant, Wikum Dinalankara, John Choi, Aanchal Jain, Ryan Nitta, Eli Yazigi et al. "The cytokine Meteorin-like inhibits anti-tumor CD8+ T cell responses by disrupting mitochondrial function." Immunity (2024). https://www.cell.com/immunity/abstract/S1074-7613(24)00352-2

“Tumor-infiltrating lymphocyte (TIL) hypofunction contributes to the progression of advanced cancers and is a frequent target of immunotherapy. Emerging evidence indicates that metabolic insufficiency drives T cell hypofunction during tonic stimulation, but the signals that initiate metabolic reprogramming in this context are largely unknown. Here, we found that Meteorin-like (METRNL), a metabolically active cytokine secreted by immune cells in the tumor microenvironment (TME), induced bioenergetic failure of CD8+ T cells. METRNL was secreted by CD8+ T cells during repeated stimulation and acted via both autocrine and paracrine signaling. Mechanistically, METRNL increased E2F-peroxisome proliferator-activated receptor delta (PPARd) activity, causingmitochondrial depolarization and decreased oxidative phosphorylation, which triggered a compensatory bioenergetic shift to glycolysis. Metrnl ablation or downregulation improved the metabolic fitness of CD8+ T cells and enhanced tumor control in several tumor models, demonstrating the translational potential of targeting the METRNL-E2F-PPARd pathway to support bioenergetic fitness of CD8+ TILs.”

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PLCL from PolySciTech used in development of Neural Interface system

 

Developing the ability to interface between brain signals and digital equipment can be highly useful for patients suffering from paralysis or other disease states limiting their bodily mobility. Researchers at Seoul National University, Dankook University, University of Ulsan, Kwangwoon University, Korea University, Northwestern University, Gyeongsang National University, Sungkyunkwan University used PLCL (AP067) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a biocompatible and flexible structure for minimally invasive implantation of a neural interface. This research holds promise to provide for improved prosthetics and other human-digital interfaces in the future. Read more: Bae, Jae-Young, Gyeong-Seok Hwang, Young-Seo Kim, Jooik Jeon, Minseong Chae, Joon-Woo Kim, Sian Lee et al. "A biodegradable and self-deployable electronic tent electrode for brain cortex interfacing." Nature Electronics (2024): 1-14. https://www.nature.com/articles/s41928-024-01216-x

“High-density, large-area electronic interfaces are a key component of brain–computer interface technologies. However, current designs typically require patients to undergo invasive procedures, which can lead to various complications. Here, we report a biodegradable and self-deployable tent electrode for brain cortex interfacing. The system can be integrated with multiplexing arrays and a wireless module for near-field communication and data transfer. It can be programmably packaged and self-deployed using a syringe for minimally invasive delivery through a small hole. Following delivery, it can expand to cover an area around 200 times its initial size. The electrode also naturally decomposes within the body after use, minimizing the impact of subsequent removal surgery. Through in vivo demonstrations, we show that our cortical-interfacing platform can be used to stimulate large populations of cortical activities.”

PLCL (Cat# AP067): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AP067#h 

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