Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA.
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Korea.
Nanoscale. 2022 Jan 6;14(2):350-360. doi: 10.1039/d1nr05738c.
Injectable shear-thinning biomaterials (STBs) have attracted significant attention because of their efficient and localized delivery of cells as well as various molecules ranging from growth factors to drugs. Recently, electrostatic interaction-based STBs, including gelatin/LAPONITE® nanocomposites, have been developed through a simple assembly process and show outstanding shear-thinning properties and injectability. However, the ability of different compositions of gelatin and LAPONITE® to modulate doxorubicin (DOX) delivery at different pH values to enhance the effectiveness of topical skin cancer treatment is still unclear. Here, we fabricated injectable STBs using gelatin and LAPONITE® to investigate the influence of LAPONITE®/gelatin ratio on mechanical characteristics, capacity for DOX release in response to different pH values, and cytotoxicity toward malignant melanoma. The release profile analysis of various compositions of DOX-loaded STBs under different pH conditions revealed that lower amounts of LAPONITE® (6NC25) led to higher pH-responsiveness capable of achieving a localized, controlled, and sustained release of DOX in an acidic tumor microenvironment. Moreover, we showed that 6NC25 had a lower storage modulus and required lower injection forces compared to those with higher LAPONITE® ratios. Furthermore, DOX delivery analysis and demonstrated that DOX-loaded 6NC25 could efficiently target subcutaneous malignant tumors DOX-induced cell death and growth restriction.
可注射的剪切稀化生物材料（STBs）由于其能够高效且局部地输送细胞以及各种分子（从生长因子到药物）而受到了广泛关注。最近，通过简单的组装工艺开发了基于静电相互作用的 STBs，包括明胶/LAPONITE®纳米复合材料，它们具有出色的剪切稀化性能和可注射性。然而，不同组成的明胶和 LAPONITE®在不同 pH 值下调节阿霉素（DOX）释放的能力，以增强局部皮肤癌治疗的效果，目前尚不清楚。在这里，我们使用明胶和 LAPONITE®制备了可注射的 STBs，以研究 LAPONITE®/明胶比例对机械特性、对不同 pH 值的 DOX 释放能力以及对恶性黑色素瘤的细胞毒性的影响。在不同 pH 条件下对不同组成的 DOX 负载 STBs 的释放曲线分析表明，较低含量的 LAPONITE®（6NC25）导致更高的 pH 响应能力，能够在酸性肿瘤微环境中实现 DOX 的局部、控制和持续释放。此外，我们表明 6NC25 具有较低的储能模量，并且与具有较高 LAPONITE®比例的相比，需要较低的注射力。此外，DOX 递送分析和细胞实验表明，负载 DOX 的 6NC25 能够有效地靶向皮下恶性肿瘤，诱导 DOX 诱导的细胞死亡和生长抑制。
