Layered Double Hydroxides Nanosheets: toward Ultrasensitive Tumor Microenvironment Responsive Synergetic Therapy

Tumor microenvironment (TME), which is featured with a high H2O2 and glutathione (GSH) level, a low pH value and hypoxia, imposes crucial influences on tumor therapeutic outcomes. Rational design and preparation of nanomaterial systems that are responsive to the intrinsic properties of TME open a promising avenue toward tumor-specific treatment. Herein, CoMn-LDHs nanosheets were synthesized via a bottom-up method followed by a surface modification with a photosensitizer Chlorin e6 (Ce6), which exhibited TME-responsive imaging as well as photodynamic and chemodynamic synergetic therapy (PDT/CDT). Due to their ultralow bond energy and large adsorption energy, CoMn-LDHs nanosheets show fast self-degradability in GSH (10 mM) microenvironment, giving an excellent CDT activity in mild acidity (pH = 6.5), superior GSH removal ability (99.82%) as well as O2 production (35.37 μg L-1 s-1). Moreover, Ce6/CoMn-LDHs nanosheets display a satisfactory PA imaging and GSH-enhanced MR imaging with a 45.1-fold T1-enhancement. In addition, both in vitro and in vivo therapeutic tests based on Ce6/CoMn-LDHs demonstrate a satisfactory anticancer activity with a complete cancer cell apoptosis and dramatic tumor elimination. This work provides a new perspective for the design of multifunctional 2D nanosheets toward a fully promoted TME-responsive synergetic therapy, which holds great promises for future clinical diagnosis and treatment.