Chemo-Magnetic Targeted Dual-Drug-Loaded Nano Polymer-Conjugate for Combined Tumor and Thrombosis Therapy.

Abstract

Most cancer patients are at high risk of thrombotic complications. However, tumor therapy combined with thrombosis treatment is a challenge due to the discrepancy in the microenvironment between tumors and thrombosis. In this study, a nano polymer-conjugate with tumor targeting and thrombolysis was developed. The nano polymer-conjugate is formed by a cross-linking agent containing imine bonds to cross-link anti-thrombosis drug nattokinase (NK) with a second-generation dendrimer (G₂) in the outer layer (NK-G₂), and magnetic silica is introduced during the cross-linking. Then, a dual drug loading system (NK-G₂)_n/FA-Dox is obtained by loading anti-tumor drug doxorubicin (Dox) modified with folic acid (FA). FA and the magnetic silica enable the nano polymer-conjugate to accumulate at the tumor sites. Most importantly, the nano polymer-conjugate shows weak acid responsiveness, allowing it to dissociate in the tumor microenvironment and release two drugs without entering cancer cells. This addresses the problem of the discrepancy in the microenvironment between tumors and thrombosis. This dual-drug loaded nano polymer-conjugate exhibits excellent potential in the combined treatment of tumor and the thrombotic complications.