Halder Satyajit, Das Tanushree, Kushwaha Ritvika, Misra Anup Kumar, Jana Kuladip, Das Debapratim
Division of Molecular Medicine, Bose Institute, P 1/12, CIT Scheme VIIM, Kolkata - 700 054 and Unified Academic Campus, EN 80, Sector V, Salt Lake City, Bidhan Nagar, Kolkata 700091, India.
Department of Chemistry, Indian Institute of Technology Guwahati, North Guwahati, Assam 781039, India.
Mater Horiz. 2025 Feb 3;12(3):987-1001. doi: 10.1039/d4mh00981a.
Harnessing the potential of hydrogel-based localized drug delivery systems holds immense promise for mitigating the systemic side effects associated with conventional cancer therapies. However, the development of such systems demands the fulfillment of multiple stringent criteria, including injectability, biocompatibility, and controlled release. Herein, we present an ultra-small peptide-based hydrogel for the sustained and targeted delivery of doxorubicin in a murine model of breast cancer. The hydrogel evades dissolution and remains stable in biological fluids, serving as a reliable drug reservoir. However, it specifically reacts to the high levels of glutathione (GSH) in the tumor microenvironment and releases drugs in a controlled manner over time for consistent therapeutic benefits. Remarkably, administration of a single dose of doxorubicin-loaded hydrogel elicited superior tumor regression (approximately 75% within 18 days) compared to conventional doxorubicin treatment alone. Furthermore, the persistent presence of the drug-loaded hydrogel near the tumor site for up to 18 days after administration highlights its enduring effectiveness. There is great clinical potential for this localized delivery strategy because of the minimal off-target effects on healthy tissues. Our findings underscore the efficacy of this smart peptide-hydrogel platform and pave the way for developing next-generation localized drug delivery systems with enhanced therapeutic outcomes in cancer treatment.
利用水凝胶基局部给药系统的潜力对于减轻传统癌症治疗相关的全身副作用具有巨大的前景。然而，开发这样的系统需要满足多个严格的标准，包括可注射性、生物相容性和控释性。在此，我们展示了一种基于超小肽的水凝胶，用于在乳腺癌小鼠模型中持续且靶向递送阿霉素。该水凝胶能避免溶解并在生物流体中保持稳定，作为一个可靠的药物储存库。然而，它能对肿瘤微环境中高水平的谷胱甘肽（GSH）做出特异性反应，并随着时间的推移以可控方式释放药物，从而带来持续的治疗益处。值得注意的是，与单独使用传统阿霉素治疗相比，单次注射载有阿霉素的水凝胶能引发更显著的肿瘤消退（18天内约75%）。此外，给药后载药水凝胶在肿瘤部位附近持续存在长达18天，突出了其持久的有效性。由于对健康组织的脱靶效应最小，这种局部递送策略具有巨大的临床潜力。我们的研究结果强调了这种智能肽 - 水凝胶平台的功效，并为开发在癌症治疗中具有更好治疗效果的下一代局部给药系统铺平了道路。
