Wednesday, February 17, 2021

PLGA from PolySciTech used in development of HER2-targeted doxycycline-based nanoparticle therapy for breast cancer.

 

With the exclusion of very specific types of breast cancer, such as triple-negative breast cancer lines, most breast cancers present human epidermal growth factor receptor 2 (HER2) marker on their surface. The use of compounds which selectively attach to this marker (such as Trastuzumab (TZB)) allows for delivery of materials specifically to the tumor cells to treat the cancer. Recently, researchers at Universidad de Guadalajara, Universidad de Sonora (Mexico), Universidad Tecnológica Metropolitana, Universidad de Chile, and Advanced Center for Chronic Diseases (Chile) used PLGA (AP081) from PolySciTech (www.polyscitech.com) to create doxycycline-loaded nanoparticles coated with HER2 targeting ligand as a treatment for breast cancer. This research holds promise to improve therapies against this potentially fatal disease in the future. Read more: Escareño, Noé, Natalia Hassan, Marcelo J. Kogan, Josué Juárez, Antonio Topete, and Adrián Daneri-Navarro. "Microfluidics-Assisted Conjugation of Chitosan-Coated Polymeric Nanoparticles with Antibodies: Significance in Drug Release, Uptake, and Cytotoxicity in Breast Cancer Cells." Journal of Colloid and Interface Science (2021). https://www.sciencedirect.com/science/article/pii/S0021979721001648

“Nanoparticle-based drug delivery systems, in combination with high-affinity disease-specific targeting ligands, provide a sophisticated landscape in cancer theranostics. Due to their high diversity and specificity to target cells, antibodies are extensively used to provide bioactivity to a plethora of nanoparticulate systems. However, controlled and reproducible assembly of nanoparticles (NPs) with these targeting ligands remains a challenge. In this context, determinants such as ligand density and orientation, play a significant role in antibody bioactivity; nevertheless, these factors are complicated to control in traditional bulk labeling methods. Here, we propose a microfluidic-assisted methodology using a PDMS (polydimethylsiloxane) Y-shaped microreactor for the covalent conjugation of Trastuzumab (TZB), a recombinant antibody targeting HER2 (human epidermal growth factor receptor 2) to doxorubicin-loaded PLGA/Chitosan NPs (PLGA/DOX/Ch NPs) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (sNHS) mediated bioconjugation reactions. Our labeling approach led to smaller and less disperse nanoparticle-antibody conjugates providing differential performance when compared to bulk-labeled NPs in terms of drug release kinetics (fitted and analyzed with DDSolver), cell uptake/labeling, and cytotoxic activity on HER2+ breast cancer cells in vitro. By controlling NP-antibody interactions in a laminar regime, we managed to optimize NP labeling with antibodies resulting in ordered coronas with optimal orientation and density for bioactivity, providing a cheap and reproducible, one-step method for labeling NPs with globular targeting moieties. Keywords: Microfluidics polymeric nanoparticles PLGA nanoparticles chitosan antibody antibody-nanoparticle conjugate”

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