Combination-Responsive MoO_3–x-Hybridized Hyaluronic Acid Hollow Nanospheres for Cancer Phototheranostics

It is of extreme importance to reduce side effects resulting from the nonspecific uptake of phototherapeutic agents by normal tissues. Currently, the single responsive strategy still cannot entirely satisfy the requirements of practical applications. In this study, we developed one kind of combination-responsive phototherapeutic nanoplatforms, where oxygen-deficient molybdenum oxide (MoO3–x) hybridized hyaluronic acid (HA) hollow nanospheres, namely, MoO3–x@HA HNSs, were constructed via a facile one-step method. In MoO3–x@HA HNSs, the reasonable combination of actively targeted specificity endowed by the HA component and tumor microenvironment-responsive phototherapy activity induced by the MoO3–x component can effectively improve the precision of phototherapy. The in vitro and in vivo experimental results confirm that MoO3–x@HA HNSs can selectively kill CD44-overexpressing cancer cells and inhibit tumor growth under an 808 nm laser irradiation, revealing their remarkable synergistic photothermal therapy/photodynamic therapy effect with CD44 receptor-targeted specificity and pH responsiveness in treating cancer. We also prove that MoO3–x@HA HNSs can serve as one kind of contrast agent to achieve the computed tomography/photoacoustic imaging. Encouraged by these results, it is anticipated that the reasonable combination of active targeting and tumor microenvironment responsiveness can be a promising strategy to develop phototherapeutic nanoplatforms for precise multimodality cancer theranostics.