Ghazizadeh Elham, Sadeghi Mahya, Deigner Hans-Peter, Neshastehriz Ali
Department of Bioinspired Materials and Biosensor Technologies, Institute of Materials Science, Faculty of Engineering, Kiel University, 24143 Kiel, Germany.
Radiation Biology Research Center, Iran University of Medical Sciences (IUMS), Tehran 1416634793, Iran.
Pharmaceutics. 2025 Jun 25;17(7):823. doi: 10.3390/pharmaceutics17070823.
Solid tumors have long presented a significant challenge in the field of oncology due to their ability to develop resistance to multiple drugs, known as multidrug resistance (MDR). This phenomenon often leads to treatment failure and poor patient outcomes. In recent years, researchers have been exploring innovative approaches to combat MDR, including the use of hydrogels for localized drug delivery. Through the biological crosslinking of an MB-smDNA-MB agent to form a pH sensitive hydrogel matrix, we introduce the injection coating of a novel PVA-MB-smDNA-MB-Mxene (PMSDMM) carrier for Adriamycin (a potent chemotherapy drug) and miR-375 (as tumor-suppressive microRNA) delivery. We aimed to enhance the effectiveness of drug delivery to solid tumors while minimizing systemic toxicity via the pH-sensitive characteristics of methylene blue at the end of smDNA as a dsDNA biological crosslinking agent, i.e., PMSDMM . Our hydrogel was shown to improve the release of the drug in the acid tumor environment. In the first 24 h, the cumulative release rate was higher at pH = 5.5 than at pH = 7.4. We show that this DNA bio-inspired PMSDMM hydrogel has potential in hydrogel injection applications for tumor suppression and tissue regeneration after the surgical resection of tumors.
实体瘤长期以来在肿瘤学领域构成重大挑战，因为它们能够对多种药物产生耐药性，即多药耐药性（MDR）。这种现象常常导致治疗失败和患者预后不佳。近年来，研究人员一直在探索对抗MDR的创新方法，包括使用水凝胶进行局部药物递送。通过将MB-smDNA-MB试剂进行生物交联以形成pH敏感水凝胶基质，我们引入了一种新型PVA-MB-smDNA-MB-Mxene（PMSDMM）载体的注射涂层，用于递送阿霉素（一种强效化疗药物）和miR-375（作为肿瘤抑制性微小RNA）。我们旨在通过作为双链DNA生物交联剂的smDNA末端亚甲蓝的pH敏感特性，提高药物递送至实体瘤的有效性，同时将全身毒性降至最低，即PMSDMM。我们的水凝胶显示出在酸性肿瘤环境中能改善药物释放。在最初的24小时内，pH = 5.5时的累积释放率高于pH = 7.4时。我们表明，这种受DNA启发的PMSDMM水凝胶在肿瘤切除术后的肿瘤抑制和组织再生的水凝胶注射应用中具有潜力。
