PLGA-PEG-Mal and PLGA-FKR648 from PolySciTech used in development of Mucin-16 cancer targeted nanoparticles

 

Targeting to cancer relies on differences between healthy cells and cancerous ones. For example, differences in mucin 16 can be used as a target moiety for drug delivery. Researchers at University of Portugal used PLGA-PEG-Mal (Cat# AI110) and PLGA-FKR648 (Cat# AV015) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles with mucin-based targeting for cancer therapy. This research holds promise to improve cancer treatments in the future. Read more: Freitas, Rui, Eduardo Ferreira, Andreia Miranda, Dylan Ferreira, Marta Relvas-Santos, Flávia Castro, Beatriz Santos et al. "Targeted and Self-Adjuvated Nanoglycovaccine Candidate for Cancer Immunotherapy." ACS nano 18, no. 14 (2024): 10088-10103. https://pubs.acs.org/doi/abs/10.1021/acsnano.3c12487

“Advanced-stage solid primary tumors and metastases often express mucin 16 (MUC16), carrying immature glycans such as the Tn antigen, resulting in specific glycoproteoforms not found in healthy human tissues. This presents a valuable approach for designing targeted therapeutics, including cancer glycovaccines, which could potentially promote antigen recognition and foster the immune response to control disease spread and prevent relapse. In this study, we describe an adjuvant-free poly(lactic-co-glycolic acid) (PLGA)-based nanoglycoantigen delivery approach that outperforms conventional methods by eliminating the need for protein carriers while exhibiting targeted and adjuvant properties. To achieve this, we synthesized a library of MUC16-Tn glycoepitopes through single-pot enzymatic glycosylation, which were then stably engrafted onto the surface of PLGA nanoparticles, generating multivalent constructs that better represent cancer molecular heterogeneity. These glycoconstructs demonstrated affinity for Macrophage Galactose-type Lectin (MGL) receptor, known to be highly expressed by immature antigen-presenting cells, enabling precise targeting of immune cells. Moreover, the glycopeptide-grafted nanovaccine candidate displayed minimal cytotoxicity and induced the activation of dendritic cells in vitro, even in the absence of an adjuvant. In vivo, the formulated nanovaccine candidate was also nontoxic and elicited the production of IgG specifically targeting MUC16 and MUC16-Tn glycoproteoforms in cancer cells and tumors, offering potential for precise cancer targeting, including targeted immunotherapies. KEYWORDS: glycovaccines nanovaccines cancer immunotherapy cancer glycosylation glycoantigens glycoconjugates”

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PEG-PLGA and PLGA-NHS from PolySciTech used in development of cancer targeting nanoparticles

 

Prostate cancer accounts for 14.9% of all new cancer cases. Researchers from Howard University used PEG-PLGA (Cat# AK029) and PLGA-NHS (Cat# AI097) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles with PSMA targeting to prostate cancer cells. This research holds promise to provide for treatment of cancer. Read more: Adekiya, Tayo Alex, Tamaro Hudson, Oladapo Bakare, Edmund E. Ameyaw, Amusa Adebayo, Oluwabukunmi Olajubutu, and Simeon K. Adesina. "PSMA-targeted combination brusatol and docetaxel nanotherapeutics for the treatment of prostate cancer." Biomedicine & Pharmacotherapy 177 (2024): 117125. https://www.sciencedirect.com/science/article/pii/S0753332224010096

“Highlights: PSMA-targeting facilitates prostate cancer-specific drug delivery. 10 % nanoparticle surface density of PSMA targeting ligand is optimal for uptake. PSMA-targeted drug-loaded particles show cytotoxicity to the cell lines tested. PSMA-targeted nanoparticles suppress tumor growth in xenograft models. Brusatol-containing nanoparticle formulations aid reduction in tumor volume. Abstract: Active targeting to cancer involves exploiting specific interactions between receptors on the surface of cancer cells and targeting moieties conjugated to the surface of vectors such that site-specific delivery is achieved. Prostate specific membrane antigen (PSMA) has proved to be an excellent target for active targeting to prostate cancer. We report the synthesis and use of a PSMA-specific ligand (Glu-NH-CO-NH-Lys) for the site-specific delivery of brusatol- and docetaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles to prostate cancer. The PSMA targeting ligand covalently linked to PLGA-PEG3400 was blended with methoxyPEG-PLGA to prepare brusatol- and docetaxel-loaded nanoparticles with different surface densities of the targeting ligand. Flow cytometry was used to evaluate the impact of different surface densities of the PSMA targeting ligand in LNCaP prostate cancer cells at 15 min and 2 h. Cytotoxicity evaluations of the targeted nanoparticles reveal differences based on PSMA expression in PC-3 and LNCaP cells. In addition, levels of reactive oxygen species (ROS) were measured using the fluorescent indicator, H2DCFDA, by flow cytometry. PSMA-targeted nanoparticles loaded with docetaxel and brusatol showed increased ROS generation in LNCaP cells compared to PC-3 at different time points. Furthermore, the targeted nanoparticles were evaluated in male athymic BALB/c mice implanted with PSMA-producing LNCaP cell tumors. Evaluation of the percent relative tumor volume show that brusatol-containing nanoparticles show great promise in inhibiting tumor growth. Our data also suggest that the dual drug-loaded targeted nanoparticle platform improves the efficacy of docetaxel in male athymic BALB/c mice implanted with PSMA-producing LNCaP cell tumors.”

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PLGA from PolySciTech used in development of ultrasound triggered delivery of genes for bone cancer treatment

 

Bone cancer is particularly difficult to treat due to its poor response to conventional chemotherapy and other, non-surgical, methods. Researchers at Chongqing Medical University used PLGA (cat# AP041) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanobubbles for transfer of genes into target cells using ultrasound. This research holds promise to provide for non-invasive therapies for bone cancer. Read more: Ren, Honglei, Shanlin Xiang, Aiguo Liu, Qian Wang, Nian Zhou, and Zhenming Hu. "A noval noninvasive targeted therapy for osteosarcoma: the combination of LIFU and ultrasound-magnetic-mediated SPIO/TP53/PLGA nanobubble." Frontiers in Bioengineering and Biotechnology 12 (2024): 1418903. https://www.frontiersin.org/articles/10.3389/fbioe.2024.1418903/full

“Purpose: Osteosarcoma (OS) is the most common type of primary malignant bone tumor. Transducing a functional TP53 gene can effectively inhibit OS cell activity. Poly lactic acid-glycolic acid (PLGA) nanobubbles (NBs) mediated by focused ultrasound (US) can introduce exogenous genes into target cells in animal models, but this technique relies on the passive free diffusion of agents across the body. The inclusion of superparamagnetic iron oxide (SPIO) in microbubbles allows for magnetic-based tissue localization. A low-intensity-focused ultrasound (LIFU) instrument was developed at our institute, and different intensities of LIFU can either disrupt the NBs (RLI-LIFU) or exert cytocidal effects on the target tissues (RHI-LIFU). Based on these data, we performed US-magnetic-mediated TP53-NB destruction and investigated its ability to inhibit OS growth when combined with LIFU both in vitro and in vivo. Methods: Several SPIO/TP53/PLGA (STP) NB variants were prepared and characterized. For the in vitro experiments, HOS and MG63 cells were randomly assigned into five treatment groups. Cell proliferation and the expression of TP53 were detected by CCK8, qRT-PCR and Western blotting, respectively. In vivo, tumor-bearing nude mice were randomly assigned into seven treatment groups. The iron distribution of Perls’ Prussian blue-stained tissue sections was determined by optical microscopy. TUNEL-DAPI was performed to examine apoptosis. TP53 expression was detected by qRT-PCR and immunohistochemistry. Results: SPIO/TP53/PLGA NBs with a particle size of approximately 200 nm were prepared successfully. For in vitro experiments, ultrasound-targeted transfection of TP53 overexpression in OS cells and efficient inhibition of OS proliferation have been demonstrated. Furthermore, in a tumor-bearing nude mouse model, RLI-LIFU-magnetic-mediated SPIO/TP53/PLGA NBs increased the transfection efficiency of the TP53 plasmid, resulting in apoptosis. Adding RHI-LIFU to the treatment regimen significantly increased the apoptosis of OS cells in vivo. Conclusion: Combining LIFU and US-magnetic-mediated SPIO/TP53/PLGA NB destruction is potentially a novel noninvasive and targeted therapy for OS.”

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PEG-PLGA from PolySciTech used in development of oral delivery system for Enfuvirtide as HIV treatment

 

Many antiviral agents have poor uptake across the intestine which limits them to only being administered by parental routes. For patient convenience, comfort, and compliance delivery by oral route is preferable. Researchers at The University of Queensland used PEG-PLGA (cat# AK026) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create oral nanoparticles for delivery of Enfuvirtide as an antiviral agent. This research holds promise to provide additional treatment for HIV/AIDS. Read more: Pang, Huiwen, Zhi Qu, Vinod Kumar, Yinuo Wang, Youzhi Wu, Min‐Hsuan Lin, David Harrich, and Felicity Y. Han. "Novel Delivery Systems for Oral Administration of Enfuvirtide: New Treatment Options for HIV/AIDS." Advanced Therapeutics (2024): 2300439. https://onlinelibrary.wiley.com/doi/abs/10.1002/adtp.202300439

“Enfuvirtide (T-20) is a synthetic peptide fusion inhibitor for the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS). However, the peptide nature limits a wider application of T-20 with subcutaneous injection (Fuzeon) the only available formulation. In this groundbreaking study, it is sought to overcome this limitation by employing poly lactic-co-glycolic acid (PLGA) and alginate to create novel oral delivery systems for T-20. Remarkably, this investigation marks the first instance of assessing the efficacy of oral delivery systems in mice. Notably, both the PLGA and alginate formulations exhibit the capability to sustain T-20 release, maintaining detectable levels in the bloodstream of mice for over 24 h after a single dose. By venturing into the realm of oral T-20 delivery, this study opens avenues for the prospective development of oral formulations of T-20, potentially leading to their evaluation in clinical trials.”

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PEG-PLA from PolySciTech used in development of intracranial delivery of drugs for brain treatment

 

Delivery of medicinal molecules into brain tissue is complicated by the blood-brain-barrier which prevents many drugs from crossing into the brain tissue. Researchers at University of Utah used PEG-PLA (cat# AK009) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nano emulsions which could be triggered through the cranium using ultrasound technology. This research holds promise to provide treatment for a variety of neurological conditions. Read more: Wilson, Matthew G., Thomas S. Riis, and Jan Kubanek. "Controlled ultrasonic interventions through the human skull." Frontiers in Human Neuroscience 18 (2024): 1412921. https://www.frontiersin.org/articles/10.3389/fnhum.2024.1412921/full

“Transcranial focused ultrasound enables precise and non-invasive manipulations of deep brain circuits in humans, promising to provide safe and effective treatments of various neurological and mental health conditions. Ultrasound focused to deep brain targets can be used to modulate neural activity directly or localize the release of psychoactive drugs. However, these applications have been impeded by a key barrier—the human skull, which attenuates ultrasound strongly and unpredictably. To address this issue, we have developed an ultrasound-based approach that directly measures and compensates for the ultrasound attenuation by the skull. No additional skull imaging, simulations, assumptions, or free parameters are necessary; the method measures the attenuation directly by emitting a pulse of ultrasound from an array on one side of the head and measuring with an array on the opposite side. Here, we apply this emerging method to two primary future uses—neuromodulation and local drug release. Specifically, we show that the correction enables effective stimulation of peripheral nerves and effective release of propofol from nanoparticle carriers through an ex vivo human skull. Neither application was effective without the correction. Moreover, the effects show the expected dose-response relationship and targeting specificity. This article highlights the need for precise control of ultrasound intensity within the skull and provides a direct and practical approach for addressing this lingering barrier.”

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PLA-PEG-PLA thermogel from PolySciTech used in development of celecoxib delivery system for treatment of breast cancer

 

Breast cancer accounts for 30% of all new cancers in women. There are 670,000 deaths per year due to this disease. Researchers at University of Oklahoma, Medical College of Wisconsin, and Thomas Jefferson University used PLA-PEG-PLA (cat# AK100) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop a thermally responsive hydrogel as a carrier of nanoparticles for delivery of celecoxib. This research holds promise to provide for improved treatment of breast cancer. Read more: Simmons, Reese, Hiroyasu Kameyama, Seiko Kubota, Yunguang Sun, John F. Langenheim, Rana Ajeeb, Tristan S. Shao et al. "Sustained delivery of celecoxib from nanoparticles embedded in hydrogel injected into the biopsy cavity to prevent biopsy-induced breast cancer metastasis." Breast Cancer Research and Treatment (2024): 1-13. https://link.springer.com/article/10.1007/s10549-024-07410-x

“Purpose: We have previously reported that protracted Cyclooxygenase-2 (COX-2) activity in bone marrow-derived cells (BMDCs) infiltrating into biopsy wounds adjacent to the biopsy cavity of breast tumors in mice promotes M2-shift of macrophages and pro-metastatic changes in cancer cells, effects which were suppressed by oral administration of COX-2 inhibitors. Thus, local control of COX-2 activity in the biopsy wound may mitigate biopsy-induced pro-metastatic changes. Methods: A combinatorial delivery system—thermosensitive biodegradable poly(lactic acid) hydrogel (PLA-gel) incorporating celecoxib-encapsulated poly(lactic-co-glycolic acid) nanoparticles (Cx-NP/PLA-gel)—was injected into the biopsy cavity of Py230 murine breast tumors to achieve local control of COX-2 activity in the wound stroma. Results: A single intra-biopsy cavity injection of PLA-gel loaded with rhodamine-encapsulated nanoparticles (NPs) showed sustained local delivery of rhodamine preferentially to infiltrating BMDCs with minimal to no rhodamine uptake by the reticuloendothelial organs in mice. Moreover, significant reductions in M2-like macrophage density, cancer cell epithelial-to-mesenchymal transition, and blood vessel density were observed in response to a single intra-biopsy cavity injection of Cx-NP/PLA-gel compared to PLA-gel loaded with NPs containing no payload. Accordingly, intra-biopsy cavity injection of Cx-NP/PLA-gel led to significantly fewer metastatic cells in the lungs than control-treated mice. Conclusion: This study provides evidence for the feasibility of sustained, local delivery of payload preferential to BMDCs in the wound stroma adjacent to the biopsy cavity using a combinatorial delivery system to reduce localized inflammation and effectively mitigate breast cancer cell dissemination. Keywords: Hydrogel, Nanoparticle, Metastasis, Biopsy, Biopsy site marker, Local drug delivery”

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mPEG-PLGA from PolySciTech used in development of RNA delivery system for control of gene expression

 

As a general rule, DNA is transcribed into single-stranded RNA which is then used to manufacture proteins. The original DNA of a cell is generally set and can not be easily edited however RNA is a dynamic process in which the single-stranded ‘message-carrier’ is constantly created, used, and destroyed. By applying messenger RNA (mRNA for transcription) of a wanted protein and silencing RNA (siRNA which selectively binds to specific coding of mRNA to prevent it from being converted to a protein) it is possible to control the expression of genes at a cellular level for a fixed period of time. Researchers at University of Ottawa used mPEG-PLGA (AK026) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles for the simultaneous delivery of mRNA and siRNA to control gene/protein expression. This research holds promise to provide for treatment of a wide range of diseases. Read more: Manturthi, Shireesha, Sara El-Sahli, Yuxia Bo, Emma Durocher, Melanie Kirkby, Alyanna Popatia, Karan Mediratta et al. "Nanoparticles co-delivering siRNA and mRNA for simultaneous restoration and silencing of gene/protein expression in vitro and in vivo." bioRxiv (2024): 2024-06. https://www.biorxiv.org/content/10.1101/2024.06.22.600196.abstract

“RNA-based agents such as siRNA, miRNA, and mRNA can selectively manipulate gene expression/proteins and have the potential to revolutionize the current therapeutic strategies for various diseases, including cancer. To address the poor stability and inherent limitations of RNA agents, nanoparticle (NP) platforms have been developed to deliver functional mRNA or siRNA inside the cells. Recent studies have focused on either siRNA to knock down proteins causing drug resistance or mRNA technology to introduce tumor suppressors. However, complex diseases like cancer need multi-targeted approaches to selectively target multiple gene expressions/proteins. In this proof-of-concept study, we developed co-delivery nanoparticles containing Luc-mRNA and siRNA-GFP as model RNA agents ((M+S)-NPs) and assessed their effects in vitro and in vivo. Our studies show that NPs can effectively deliver both functional mRNA and siRNA together, simultaneously impacting the expression of two genes/proteins in vitro. Additionally, after in vivo administration, co-delivery NPs successfully knocked down GFP while introducing luciferase in a TNBC mouse model, indicating our NPs have the potential to develop RNA-based anticancer therapeutics. These studies pave the way to develop RNA-based, multitargeted, multi-delivery approaches for complex diseases like cancer. Keywords: nanoparticles, siRNA, mRNA, co-delivery, gene, protein, restoration and knockdown.”

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