Heat/pH-boosted release of 5-fluorouracil and albumin-bound paclitaxel from Cu-doped layered double hydroxide nanomedicine for synergistical chemo-photo-therapy of breast cancer

• Published in: Journal of controlled release Vol. 335; pp. 49 - 58
• Main Authors: Liu, Jianping, Liu, Kai, Zhang, Liming, Zhong, Ming, Hong, Tingliang, Zhang, Run, Gao, Yufan, Li, Rui, Xu, Tiefeng, Xu, Zhi Ping
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.07.2021
• Subjects: Chemotherapy; Combination breast cancer treatment; Heat/pH-triggered drug release; Layered double hydroxide; Photothermal therapy; Photothermal therapy; Chemotherapy; Heat/pH-triggered drug release; Combination breast cancer treatment; Layered double hydroxide
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2021.05.011

Considerable attention has been devoted to nanomedicine development for breast cancer therapy, while the therapeutic efficiency is far from satisfactory owing to non-specific biodistribution-caused side effects and limitation of single modal treatment. In this study, we have developed a novel nanomedicine for efficient combination breast cancer therapy. This nanomedicine was based on copper-doped layered double hydroxide (Cu-LDH) nanoparticles loaded with two FDA-approved anticancer drugs, i.e. 5-fluorouracil (5-FU) and albumin-bound paclitaxel (nAb-PTX) with complementary chemotherapeutic actions. The 5-FU/Cu-LDH@nAb-PTX nanomedicine showed pH-sensitive heat-facilitated therapeutic on-demand release and demonstrated the moderate-to-strong synergy of photothermal therapy and chemotherapy in inducing apoptosis of breast cancer cells (4 T1). This nanomedicine had a high colloidal stability in saline and serum, and efficiently accumulated in the tumor tissue. Remarkably, this nanomedicine nearly eliminated 4 T1 tumors in vivo after a two-course treatment under mild 808 nm laser irradiation (0.75 W/cm2, 3 min) at very low doses of 5-FU and nAb-PTX (0.25 and 0.50 mg/kg, 8–50 times less than that used in other nanoformulations), without observable side effects. Therefore, this research provides a novel approach to designing multifunctional nanomedicines for on-demand release of chemotherapeutics to cost-effectively treat breast cancer with minimal side effects in future clinic applications. [Display omitted] •Trimodal nanomedicine 5-FU/Cu-LDH@nAb-PTX reproducibly constructed•The nanomedicine had a high photothermal conversion of 808 nm NIR.•Weak acidity and mild heat trigger 5-FU/PTX burst release for synergistical therapy•Near elimination of breast tumor under mild NIR light at very low therapeutic doses•Promising cancer chemo-photo-immunotherapy