Engineering optimal gold nanorod-loaded hollow mesoporous organosilica nanotheranostics for NIR-II photoacoustic microscopy imaging and tumor synergistic therapy

• A miniature gold nanorod-loaded hollow mesoporous organosilica nanotheranostic (HMON) with tunable cavity is designed. • The Au@HMON can serve as an NIR-II contrast agent for PAM imaging. • The 221 nm-nanotheranostic exhibited stronger PAM signal and higher drug loading efficacy than its small counterparts. • AuNR endows the nanotheranostics with a high photothermal conversion efficiency of 41 % for hyperthermia. • PAM imaging and synergistic therapeutic efficacy of nanotheranostics are demonstrated in a mouse model. Biodegradable hollow mesoporous organosilica nanoparticles (HMON)-based nanotheranostics has recently gained growing interests due to their tremendous potential as an attractive platform for cancer imaging and therapy. However, the engineering of HMON-based nanotheranostics for size-dependent biological profile on in vivo tumor uptake, biodistribution and retention in tumor region have not been achieved to date. Here, a novel tumor microenvironment (TME)-activated nanoplatform employing miniature gold nanorod-loaded HMON (Au@HMON) with tunable hollow cavity of HMON coating is presented, and its application in the second near infrared (NIR-II, 1000–1700 nm) window photoacoustic microscopy (PAM) imaging-guided synergistic chemo-photothermal therapy is studied by loading doxorubicin (DOX). The cancer cell membrane (CCM) biomimetic nanotheranostics (Au@HMON-DOX@CCM) exhibited a high photothermal conversion efficiency of 41.1 % for photothermal therapy (PTT) and PAM imaging. Among the three investigated nanotheranostics, the 221 nm-nanotheranostics exhibited stronger PAM signal and higher drug loading efficacy than the small counterparts (156- and 186-nm) due to the thicker HMON coating layer, larger surface area and intermediate void structure. Therefore, synergistic chemo-photothermal therapy using 221 nm-nanotheranostics is achieved to efficiently inhibit tumor growth. This strategy affords design parameters for engineering HMON-based “all-in-one” nanotheranostics for photoacoustic imaging-guided cancer treatment.