TY - JOUR
T1 - PH-Responsive doxorubicin delivery using shear-thinning biomaterials for localized melanoma treatment
AU - Lee, Junmin
AU - Wang, Yonggang
AU - Xue, Chengbin
AU - Chen, Yi
AU - Qu, Moyuan
AU - Thakor, Jai
AU - Zhou, Xingwu
AU - Barros, Natan Roberto
AU - Falcone, Natashya
AU - Young, Patric
AU - van den Dolder, Floor W.
AU - Lee, KangJu
AU - Zhu, Yangzhi
AU - Cho, Hyun-Jong
AU - Sun, Wujin
AU - Zhao, Bo
AU - Ahadian, Samad
AU - Jucaud, Vadim
AU - Dokmeci, Mehmet R.
AU - Khademhosseini, Ali
AU - Kim, Han-Jun
N1 - Funding Information: The authors gratefully acknowledge funding from the National Institutes of Health (HL140951, HL137193, and CA233981). Publisher Copyright: © The Royal Society of Chemistry.
PY - 2022
Y1 - 2022
N2 - 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. This journal is
AB - 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. This journal is
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85122883520&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/34908077
U2 - https://doi.org/10.1039/d1nr05738c
DO - https://doi.org/10.1039/d1nr05738c
M3 - Article
C2 - 34908077
SN - 2040-3364
VL - 14
SP - 350
EP - 360
JO - Nanoscale
JF - Nanoscale
IS - 2
ER -