Fluorescently labelled PLGA from PolySciTech used in development of cell-modulating system for cancer immunotherapy

 

Delivery of drugs into solid tumors as well as cancers immunosuppressive effect on the surrounding microenvironment makes treatment of cancer challenging. One strategy to overcome this is to utilize a surface-attaching structure which promotes immune cells in the region of cancer to become pro-inflammatory and anti-tumor thus leading the human immune system to fight the cancer. Researchers at Harvard University used PLGA-rhodamine (AV011) and PLGA-Cyanine5 (AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop ‘backpacks’ small structures which attach to myeloid cells and encourages them to participate in immune attack of cancer. This research holds promise to treat many forms of aggressive cancer including immunosuppressive tumors. Read more: Kapate, Neha, Michael Dunne, Alexander P. Gottlieb, Malini Mukherji, Vineeth Chandran Suja, Supriya Prakash, Kyung Soo Park, Ninad Kumbhojkar, Jennifer L. Guerriero, and Samir Mitragotri. "Polymer Backpack‐loaded Tissue Infiltrating Monocytes for Treating Cancer." Advanced Healthcare Materials (2024): 2304144. https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.202304144

“Adoptive cell therapies are dramatically altering the treatment landscape of cancer. However, treatment of solid tumors remains a major unmet need, in part due to limited adoptive cell infiltration into the tumor and in part due to the immunosuppressive tumor microenvironment. The heterogeneity of tumors and presence of non-responders also calls for development of antigen-independent therapeutic approaches. Myeloid cells offer such an opportunity, given their large presence in the immunosuppressive tumor microenvironment, such as in triple negative breast cancer. However, their therapeutic utility is hindered by their phenotypic plasticity. Here, we leverage the impressive trafficking ability of adoptively transferred monocytes into the immunosuppressive 4T1 tumor to develop an anti-tumor therapy. To control monocyte differentiation in the tumor microenvironment, we developed surface-adherent “backpacks” stably modified with IFNγ to stimulate macrophage plasticity into a pro-inflammatory, anti-tumor phenotype, a strategy we refer to as Ornate Polymer-backpacks on Tissue Infiltrating Monocytes (OPTIMs). Treatment with OPTIMs substantially reduced tumor burden in a mouse 4T1 model and significant increased survival. Cytokine and immune cell profiling revealed that OPTIMs remodeled the tumor microenvironment into a pro-inflammatory state.”

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mPEG-PLGA from PolySciTech used in development of PARP/Kinase inhibitor drug delivery systems against cancer

 

There are a wide range of anticancer agents which prevent tumor growth by inhibiting cellular functions. PARP inhibitors, for example, prevent cancer cells from repairing strand breaks in their DNA structures leading to eventual cell death. Additionally, cyclin dependent kinase inhibitors prevent the cell from responding to DNA damage thus amplifying the effect of PARP inhibitors. Drugs based on interfering with the cellular operations of cancer cells can be effective at stopping tumor growth, but can also have serious side effects against healthy cells. Researchers at Northeastern University and Harvard Medical School used mPEG-PLGA (Cat# AK010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a nanoparticle delivery system combining the effects of a kinase inhibitor and a PARP inhibitor and tested the efficacy of this system against cancer cells. This research holds promise to provide for improved therapy against cancer in the future. Read more: Baldwin, Paige, Shicheng Yang, Adrienne Orriols, Sherrie Wang, Needa Brown, and Srinivas Sridhar. "A nano-cocktail of the PARP inhibitor talazoparib and CDK inhibitor dinaciclib for the treatment of triple negative breast cancer." Cancer Nanotechnology 15, no. 1 (2024): 1-16. https://cancer-nano.biomedcentral.com/articles/10.1186/s12645-023-00240-4

“The addition of the cyclin dependent kinase inhibitor (CDKi) dinaciclib to Poly-(ADP-ribose) polymerase inhibitor (PARPi) therapy is a strategy to overcome resistance to PARPi in tumors that exhibit homologous recombination (HR) deficiencies as well as to expand PARPi therapy to tumors that do not exhibit HR deficiencies. However, combination therapy using pathway inhibitors has been plagued by an inability to administer doses sufficient to achieve clinical benefit due to synergistic toxicities. Here we sought to combine nanoformulations of the PARPi talazoparib, nTLZ, and the CDKi dinaciclib, nDCB, in a nano-cocktail to enhance therapeutic efficacy while maintaining lower doses. Pharmacokinetics of nDCB were assessed to ensure it is compatible with nTLZ. nDCB was combined with nTLZ to generate a nano-cocktail nDCB:nTLZ, which elicits greater cell death in vitro compared to the combination of the free drugs. MDA-MB-231-LUC-D3H2LN xenografts were utilized to assess therapeutic efficacy of the nano-cocktail in terms of tumor progression. Administration of the nano-cocktail significantly slowed tumor progression in the HR proficient animal model compared to administration of free talazoparib and free dinaciclib at the same doses. Histology of the liver, spleen, and kidneys revealed long-term treatment did not induce nanoparticle associated morphological changes. Complete blood count did not reveal any significant hematologic changes after treatment with either the free combination or nano-cocktail. The efficacy and toxicity data suggest that further dose escalation can be pursued in order to achieve a stronger response. These data suggest the administration of combination therapy through the nano-cocktail leads to a better response than the use of free compounds and is a promising strategy for implementing combination therapy in the clinic.”

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PLGA from PolySciTech used in development of cartilage tissue regeneration for arthritis treatment

 

Arthritis is an inflammatory disease that affects about 1 in 5 USA adults (CDC National statistics). The immune system attacks cartilage in the joints which initially causes pain and stiffness but can lead to loss of functionality of the joint. Researchers at Universidade do Porto (Portugal) SINTEF Industry (Norway), Ulm University Medical Center Ulm (Germany), and Askel Healthcare Ltd (Finland) used PLGA from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop anti-inflammatory nanoparticles to work with a scaffold system for treatment of arthritis. This research holds promise to improve treatment of this debilitating disease. Read more: Pereira Vasconcelos, Daniela, Catarina Leite Pereira, Marina Couto, Estrela Neto, Beatriz Ribeiro, Filipe Albuquerque, Alexandra Freitas et al. "Nanoenabled Immunomodulatory Scaffolds for Cartilage Tissue Engineering." Advanced Functional Materials (2024): 2400627. https://onlinelibrary.wiley.com/doi/abs/10.1002/adfm.202400627

“Articular cartilage regeneration is a challenge in tissue engineering. Although diverse materials have been developed for this purpose, cartilage regeneration remains suboptimal. The integration of nanomaterials into 3D network materials holds great potential in the improvement of key mechanical properties, particularly important for osteochondral replacement scaffolds and even to function as carriers for disease-modifying drugs or other regulatory signals. In this study, a simple yet effective cell-free nanoenabled Col-PLA scaffold specially designed to enhance cartilage regeneration and modulate inflammatory response is proposed, by incorporating poly(lactic-co-glycolic acid) (PLGA) ibuprofen nanoparticles (NPs) into a collagen/polylactide (Col-PLA) matrix. The developed nanoenabled scaffold successfully decreases IL-1β release and leads to primary human chondrocytes survival, ultimately restoring extracellular matrix (ECM) production under inflammatory conditions. The nanoenabled Col-PLA scaffolds secretome effectively decreases macrophage invasion in vitro, as well as neutrophil infiltration and inflammatory mediators’, namely the complement component C5/C5a, C-reactive protein, IL-1β, MMP9, CCL20, and CXCL1/KC production in vivo in a rodent air-pouch model. Overall, the established nanoenabled scaffold has the potential to support chondrogenesis as well as modulate inflammatory response, overcoming the limitations of traditional tissue engineering strategies.”

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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).

PLGA-Rhodamine from PolySciTech used in development of siRNA-loaded nanoparticles for Alzheimer's treatment.

 

Alzheimer’s disease is a chronic degenerative disorder characterized by deposition of extracellular amyloid plaques within the brain leading to cognitive decline. Researchers at Korea Institute of Science and Technology, Kyung Hee University, Chungnam National University, Catholic Kwandong University, Soonchunhyang University, and Seoul National University used PLGA-rhodamine (cat# AV027) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles to deliver siRNA. This research holds promise to improve treatment against Alzheimer’s disease. Read more: Shin, Hyo Jung, In Soo Kim, Seung Gyu Choi, Kayoung Lee, Hyewon Park, Juhee Shin, Dayoung Kim et al. "Rejuvenating aged microglia by p16ink4a-siRNA-loaded nanoparticles increases amyloid-β clearance in animal models of Alzheimer’s disease." Molecular Neurodegeneration 19, no. 1 (2024): 25. https://link.springer.com/article/10.1186/s13024-024-00715-x

“Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer’s disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance. First, we used gene ontology analysis of microglia from young and old mice to identify differential expression of cyclin-dependent kinase inhibitor 2A (p16ink4a), a cell cycle factor related to aging. We found that p16ink4a expression was increased in microglia near amyloid plaques in brain tissue from patients with AD and 5XFAD mice, a model of AD. In BV2 microglia, small interfering RNA (siRNA)-mediated p16ink4a downregulation transformed microglia with enhanced amyloid phagocytic capacity through regulated the cell cycle and increased cell proliferation. To regulate microglial phagocytosis by gene transduction, we used poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles, which predominantly target microglia, to deliver the siRNA and to control microglial reactivity. Nanoparticle-based delivery of p16ink4a siRNA reduced amyloid plaque formation and the number of aged microglia surrounding the plaque and reversed learning deterioration and spatial memory deficits. We propose that downregulation of p16ink4a in microglia is a promising strategy for the treatment of Alzheimer’s disease. Keywords Alzheimer’s disease, Microglia senescence, Phagocytosis, p16ink4a, Cell cycle”

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PLGA from PolySciTech used in development of Ursolic acid delivery nanoparticles for treatment of breast cancer

 

Breast cancer is the most common cancer in women in the United States accounting for approximately 30% of all new female cancers each year (American Cancer Society). Researchers at Mahidol University and Khon Kaen University (Thailand) used PLGA (Cat# AP059) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create and test the efficacy of chitosan-coated nanoparticles loaded with ursolic acid. This research holds promise to provide for improved cancer therapies in the future. Read more: Payomhom, Pattaree, Nattawadee Panyain, Chadamas Sakonsinsiri, Patompon Wongtrakoongate, Kornkamon Lertsuwan, Dakrong Pissuwan, and Kanlaya Prapainop Katewongsa. "Chitosan-Coated Poly (lactic-co-glycolic acid) Nanoparticles Loaded with Ursolic Acid for Breast Cancer Therapy." ACS Applied Nano Materials (2024). https://pubs.acs.org/doi/abs/10.1021/acsanm.3c06161

“Ursolic acid (UA), a pentacyclic triterpenoid found in various fruits and herbs, has the potential as an anticancer agent against multiple cancer types. Nevertheless, its clinical use was limited by its poor water solubility. To overcome this drawback, several nanocarriers were proposed to increase the bioavailability and efficacy of UA. However, the insights into the cellular targets and mechanisms of UA and UA nanoparticles (NPs) remain limited. In this study, chitosan-coated poly(lactic-co-glycolic acid) (PLGA/CS) NPs were loaded with UA. The obtained (UA)-PLGA/CS NPs were spherical with an approximate size of 250 nm and an encapsulation efficiency of 25%. Owing to their promising potential as drug carriers, the NPs were successfully delivered into breast cancer cells (MCF-7 and MDA-MB-231). Moreover, (UA)-PLGA/CS NPs enhanced the anticancer activity of UA, as evidenced by the IC50 values of 26.74 and 40.67 μM in MCF-7 and MDA-MB-231 cells, respectively. These values were lower than those of free UA (90.25 and 85.63 μM in MCF-7 and MDA-MB-231 cells, respectively). The improved cytotoxicity induced by (UA)-PLGA/CS NPs can be attributed to apoptosis induction, collective cell migration and invasion inhibition, and cell proliferation pathway disruption. These findings led to a better understanding of the anticancer effects and molecular mechanisms of (UA)-PLGA/CS NPs and their potential targets for breast cancer therapy. KEYWORDS: ursolic acid nanoparticles PLGA chitosan breast cancer”

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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).

PEG-PLGA from PolySciTech used in the development of nanoparticles to deliver anti-tumor agents RG7388 and entinostat for cancer therapy

 

In cancer therapy applications it is possible for specific drugs to work in concert creating a stronger effect than either of them would have on their own. Due to their interactions on several biological pathways, there is good indication that recently discovered RG7388 compound can work with entinostat to treat cancer. Researchers at Queen’s University Belfast and Al-Ahliyya Amman University used PEG-PLGA (Cat# AK010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create and test the efficacy of nanoparticles loaded with both drugs. This research holds promise to improve cancer therapy in the future. Read more: Abed, Anas, Michelle K. Greene, Alhareth A. Alsa’d, Andrea Lees, Andrew Hindley, Daniel B. Longley, Simon S. McDade, and Christopher J. Scott. "Nanoencapsulation of MDM2 Inhibitor RG7388 and Class-I HDAC Inhibitor Entinostat Enhances their Therapeutic Potential Through Synergistic Antitumor Effects and Reduction of Systemic Toxicity." Molecular Pharmaceutics (2024). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.3c00926

“Inhibitors of the p53–MDM2 interaction such as RG7388 have been developed to exploit latent tumor suppressive properties in p53 in 50% of tumors in which p53 is wild-type. However, these agents for the most part activate cell cycle arrest rather than death, and high doses in patients elicit on-target dose-limiting neutropenia. Recent work from our group indicates that combination of p53–MDM2 inhibitors with the class-I HDAC inhibitor Entinostat (which itself has dose-limiting toxicity issues) has the potential to significantly augment cell death in p53 wild-type colorectal cancer cells. We investigated whether coencapsulation of RG7388 and Entinostat within polymeric nanoparticles (NPs) could overcome efficacy and toxicity limitations of this drug combination. Combinations of RG7388 and Entinostat across a range of different molar ratios resulted in synergistic increases in cell death when delivered in both free drug and nanoencapsulated formats in all colorectal cell lines tested. Importantly, we also explored the in vivo impact of the drug combination on murine blood leukocytes, showing that the leukopenia induced by the free drugs could be significantly mitigated by nanoencapsulation. Taken together, this study demonstrates that formulating these agents within a single nanoparticle delivery platform may provide clinical utility beyond use as nonencapsulated agents. KEYWORDS:cancer nanoparticles Entinostat nutlin toxicity combination therapy”

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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).

PLGA-PEG-Dibenzocyclooctyne from PolySciTech used in research on PARPi treatment for ovarian cancer.

 

On average, about 12,740 women die from ovarian cancer each year in USA (American Cancer Society).Researchers at University of Maryland used PLGA-PEG-COOH (AI171) and PLGA-PEG-DBCO (AI205) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles loaded with talazoparib as a strategy to treat chemotherapy resistant ovarian cancer. This research holds promise to improve cancer therapy in the future. Read more: Sorrin, Aaron, Anika Dasgupta, Kathryn McNaughton, Carla Arnau Del Valle, Keri Zhou, Cindy Liu, Dana M. Roque, and Huang Chiao Huang. "Co-Packaged PARP inhibitor and photosensitizer for targeted photo-chemotherapy of 3D ovarian cancer spheroids." Cell & Bioscience 14, no. 1 (2024): 1-13. https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-024-01197-6

“Background: Within the last decade, poly(ADP-ribose) polymerase inhibitors (PARPi) have emerged in the clinic as an effective treatment for numerous malignancies. Preclinical data have demonstrated powerful combination effects of PARPi paired with photodynamic therapy (PDT), which involves light-activation of specialized dyes (photosensitizers) to stimulate cancer cell death through reactive oxygen species generation. Results: In this report, the most potent clinical PARP inhibitor, talazoparib, is loaded into the core of a polymeric nanoparticle (NP-Tal), which is interfaced with antibody-photosensitizer conjugates (photoimmunoconjugates, PICs) to form PIC-NP-Tal. In parallel, a new 3D fluorescent coculture model is developed using the parental OVCAR-8-DsRed2 and the chemo-resistant subline, NCI/ADR-RES-EGFP. This model enables quantification of trends in the evolutionary dynamics of acquired chemoresistance in response to various treatment regimes. Results reveal that at a low dosage (0.01 μM), NP-Tal kills the parental cells while sparing the chemo-resistant subline, thereby driving chemoresistance. Next, PIC-NP-Tal and relevant controls are evaluated in the 3D coculture model at multiple irradiation doses to characterize effects on total spheroid ablation and relative changes in parental and subline cell population dynamics. Total spheroid ablation data shows potent combination effects when PIC and NP-Tal are co-administered, but decreased efficacy with the conjugated formulation (PIC-NP-Tal). Analysis of cell population dynamics reveals that PIC, BPD + NP-Tal, PIC + NP-Tal, and PIC-NP-Tal demonstrate selection pressures towards chemoresistance. Conclusions: This study provides key insights into manufacturing parameters for PARPi-loaded nanoparticles, as well as the potential role of PDT-based combination therapies in the context of acquired drug resistance.”


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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a​ free ​scientific/​networking conference hosted by Akina (http://bprconference.com/​).