A functionalized cell membrane biomimetic nanoformulation based on layered double hydroxide for combined tumor...

The development of nanoformulations with simple compositions that can exert targeted combination therapy still remains a great challenge in the area of precision cancer nanomedicine. Herein, we report the design of a multifunctional nanoplatform based on methotrexate (MTX)-loaded layered double hydroxide (LDH) coated with chlorin e6 (Ce6)-modified MCF-7 cell membranes (CM_M) for combined chemo/sonodynamic therapy of breast cancer. LDH nanoparticles were in situ loaded with MTX via coprecipitation, and coated with CM_M that were finally functionalized with phospholipid-modified Ce6. The created nanoformulation of LDH-MTX@CM_M-Ce6 displays good colloidal stability under physiological conditions and can release MTX in a pH-dependent manner. We show that the formulation can homologously target breast cancer cells, and induce their significant apoptosis through arresting the cell cycle via cooperative MTX-based chemotherapy and ultrasound (US)-activated sonodynamic therapy. The assistance of US can not only trigger sonosensitizer Ce6 to produce reactive oxygen species, but also enhance the cellular uptake of LDH-MTX@CM_M-Ce6 via an acoustic cavitation effect. Upon intravenous injection and US irradiation, LDH-MTX@CM_M-Ce6 displays an admirable antitumor performance towards a xenografted breast tumor mouse model. Furthermore, the modification of Ce6 on the CM_M endows the LDH-based nanoplatform with fluorescence imaging capability. The developed LDH-based nanoformulation here provides a general intelligent cancer nanomedicine platform with simple composition and homologous targeting specificity for combined chemo/sonodynamic therapy and fluorescence imaging of tumors.