mPEG-PCL from PolySciTech used in development of SiRNA targeted delivery for cancer therapy

 

One strategy to treat cancer is to modify the tumor microenvironment so that the immune system is more likely to attack the cancer. Researchers at Ludwig-Maximilians-University Munich, Daiichi Sankyo Europe GmbH, University of Augsburg, Nanotemper Technologies GmbH, University of Augsburg, and Daiichi Sankyo Europe GmbH used mPEG-PCL (cat# AK073) from PolySciTech division of Akina, Inc. (www.polyscitech.com) as part of research into SiRNA delivery to macrophages. This research holds promise to improve therapy against cancer. Read more: Jürgens, David C., Benjamin Winkeljann, Miriam Kolog Gulko, Yao Jin, Judith Möller, Joshua Winkeljann, Sahana Sheshachala et al. "Efficient and Targeted siRNA Delivery to M2 Macrophages by Smart Polymer Blends for M1 Macrophage Repolarization as a Promising Strategy for Future Cancer Treatment." ACS Biomaterials Science & Engineering (2023). https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.3c01595

“Cancer remains an issue on a global scale. It is estimated that nearly 10 million people succumbed to cancer worldwide in 2020. New treatment options are urgently needed. A promising approach is a conversion of tumor-promoting M2 tumor-associated macrophages (TAMs) as part of the tumor microenvironment to tumor-suppressive M1 TAMs by small interfering RNA (siRNA). In this work, we present a well-characterized polymeric nanocarrier system capable of targeting M2 TAMs by a ligand–receptor interaction. Therefore, we developed a blended PEI-based polymeric nanoparticle system conjugated with mannose, which is internalized after interaction with macrophage mannose receptors (MMRs), showing low cytotoxicity and negligible IL-6 activation. The PEI–PCL–PEI (5 kDa–5 kDa–5 kDa) and Man-PEG–PCL (2 kDa–2 kDa) blended siRNA delivery system was optimized for maximum targeting capability and efficient endosomal escape by evaluation of different polymer and N/P ratios. The nanoparticles were formulated by surface acoustic wave-assisted microfluidics, achieving a size of ∼80 nm and a zeta potential of approximately +10 mV. Special attention was given to the endosomal escape as the so-called bottleneck of RNA drug delivery. To estimate the endosomal escape capability of the nanocarrier system, we developed a prediction method by evaluating the particle stability via the inflection temperature. Our predictions were then verified in an in vitro setting by applying confocal microscopy. For cellular experiments, however, human THP-1 cells were polarized to M2 macrophages by cytokine treatment and validated through MMR expression. To show the efficiency of the nanoparticle system, GAPDH and IκBα knockdown was performed in the presence or absence of an MMR blocking excess of mannan. Cellular uptake, GAPDH knockdown, and NF-κB western blot confirmed efficient mannose targeting. Herein, we presented a well-characterized nanoparticle delivery system and a promising approach for targeting M2 macrophages by a mannose–MMR interaction. KEYWORDS: M2 tumor-associated macrophages siRNA macrophage mannose receptors microfluidics surface acoustic waves polymer blends”