Colorectal cancer (CRC) remains one of the most prevalent cancers with high mortality rates globally. There is limited potential for therapy due to toxic side effects from systemic delivery of chemotherapeutics. Researchers at Pusan National University and Korea University used PLGA (AP037) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to chemically conjugate hyaluronic acid and irinotecan together to make prodrug nanoconjugates. This research holds promise to provide for treatment of colorectal cancer. Read more: Lee, Juho, Jihyun Kim, Dongmin Kwak, Hyunwoo Kim, Muneeb Ullah, Min Chan Kim, Kyu Hyun et al. "On-site sol-gel-sol transition of alginate enables reversible shielding/deshielding of tumor cell-activated nanoconjugates for precise local colorectal cancer therapy." Chemical Engineering Journal 505 (2025): 158935. https://www.sciencedirect.com/science/article/pii/S1385894724104263
“Highlights: Alg/CTNCs were developed as an orally administrable precise local CRC therapeutic. Alg/CTNCs exhibited on-site sol-gel-sol transition during GI tract passage. Interactions with the small intestinal epithelium and premature drug loss were prevented. In the colorectum, CTNCs liberated from Alg/CTNCs selectively accumulated in CRC tissues. Tumor esterase facilitated drug release from the CTNCs, resulting in potent antitumor effects. Abstract: Although local colorectal cancer (CRC) therapy can be achieved by delivering CRC-targeted nanoparticles directly to the tumor tissues within the colorectal cavity, bypassing systemic circulation through the oral administration route, physical entrapment of the nanoparticles by the small intestinal epithelium, and premature drug loss before reaching the colorectal cavity results in limited local therapeutic efficacy. To overcome these limitations, this study aimed to develop CRC cell-activated nanoconjugates (CTNCs)-in-alginate (Alg/CTNCs). After oral administration, Alg/CTNCs undergo a sol-gel transition upon exposure to gastric acid, and the alginate gel matrix effectively shields the incorporated CTNCs, preventing unwanted interactions with the intestinal epithelium and drug loss before reaching the colorectum. Upon reaching the colorectum, the elevated pH triggers a gel-sol transition in the gelated Alg/CTNCs, and the deshielded CTNCs from the alginate gel matrix show highly CRC-selective accumulation. Finally, drugs are released in response to intracellular esterase, ultimately leading to potent local antitumor effects without systemic side effects. These findings suggest that the reversible shielding/deshielding of nanomaterials during gastrointestinal tract passage, along with intratumoral environment-activated drug release strategies, enables precise local CRC therapy.”
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