PH-Responsive doxorubicin delivery using shear-thinning biomaterials for localized melanoma treatment. Issue 2 (15th December 2021)

• Record Type: Journal Article
• Authors: Lee, Junmin; Wang, Yonggang; Xue, Chengbin; Chen, Yi; Qu, Moyuan; Thakor, Jai; Zhou, Xingwu; Barros, Natan Roberto; Falcone, Natashya; Young, Patric; van den Dolder, Floor W.; Lee, KangJu; Zhu, Yangzhi; Cho, Hyun-Jong; Sun, Wujin; Zhao, Bo; Ahadian, Samad; Jucaud, Vadim; Dokmeci, Mehmet R.; Khademhosseini, Ali; Kim, Han-Jun
• Is Part Of: Nanoscale. Volume 14:Issue 2(2022)
• Page Start: 350
• Page End: 360
• Publication Date: 2021-12-15
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d1nr05738c
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : 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. Abstract : 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 in vitro and in vivo demonstrated that DOX-loaded 6NC25 could efficiently target subcutaneous malignant tumors via DOX-induced cell death and growth restriction.