Gangrade Ankit, Mandal Biman B
Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.
Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.
ACS Biomater Sci Eng. 2020 Nov 9;6(11):6195-6206. doi: 10.1021/acsbiomaterials.0c01043. Epub 2020 Oct 9.
Localized cancer chemotherapy through injectable hydrogels is a next-generation advanced substitute for the currently operational systemic route of drug administration. Recently, several hydrogels have been developed for prospective drug delivery applications; however, no disease model is available to evaluate its long-term bioactivity in real time. In this regard, we have designed a porous silk scaffold that provides a single platform to accommodate both the soft hydrogel and cancer cells together. The stomach cancer (AGS) cells were seeded in the periphery of the silk scaffold, where they sit in the pores and form three-dimensional (3D) spheroids. Furthermore, the anticancer drug cisplatin-loaded nanocomposite injectable silk hydrogel was filled in the central cavity of the scaffold to evaluate its 11 day extended bioactivity. Such an arrangement keeps the released cisplatin in close contact with the spheroids for its sustained therapeutic effects. In an attempt to model cancer recurrence, the AGS cells were reseeded on the second day of treatment. Our data revealed that the shelf life and cytotoxic effects of cisplatin, which was explicitly releasing out from the nanocomposite silk hydrogel, were considerably enhanced. Hence, the reseeded AGS cells did not survive further on the scaffold, which also indicates its ability to inhibit cancer relapse. Conclusively, the current work showed a possible way to evaluate the long-term efficacy and bioactivity of the injectable hydrogel system for sustained drug delivery application.
通过可注射水凝胶进行局部癌症化疗是目前正在使用的全身给药途径的下一代先进替代方案。最近，已经开发出几种水凝胶用于未来的药物递送应用；然而，目前还没有疾病模型可用于实时评估其长期生物活性。在这方面，我们设计了一种多孔丝支架，它提供了一个单一平台，可同时容纳柔软的水凝胶和癌细胞。将胃癌（AGS）细胞接种在丝支架的周边，它们位于孔隙中并形成三维（3D）球体。此外，将负载抗癌药物顺铂的纳米复合可注射丝水凝胶填充到支架的中心腔中，以评估其长达11天的延长生物活性。这种布置使释放的顺铂与球体保持紧密接触，以实现其持续的治疗效果。为了模拟癌症复发，在治疗的第二天重新接种AGS细胞。我们的数据显示，从纳米复合丝水凝胶中明确释放出来的顺铂的保质期和细胞毒性作用得到了显著增强。因此，重新接种的AGS细胞在支架上无法继续存活，这也表明其具有抑制癌症复发的能力。总之，目前的工作展示了一种评估可注射水凝胶系统在持续药物递送应用中的长期疗效和生物活性的可能方法。
