<p>Premature drug release and poor controllability present significant challenges in the practical application of cancer therapy, often resulting in reduced chemotherapy effectiveness and severe side effects. A key limitation of current anticancer nanocarriers lies in reconciling multiple functionalities with biodegradability and favorable biocompatibility. To meet these challenges, herein, we have synthesized novel trimetallic (Cu, Fe, Zn) squarate based MOF (^STM) and L-ascorbate based MOF (^LTM) by a simple solvothermal approach under controlled reaction conditions. Furthermore, polydopamine (PDA) wrapped MOF composite hollow nanoparticles were fabricated by utilizing silica nanoparticles as a template to enhance drug encapsulation capacity and controlled drug release. Both of the trimetallic MOF showed irregular morphology with layered structure and after decorated with PDA, ^SPTM and ^LPTM exhibited spherical shape with size of around 100&#xa0;nm confirmed with scanning electron microscopy. Both newly synthesized trimetallic MOF, ^SPTM@DOX and ^LPTM@DOX showed high DOX loading efficiency 98.45, and 99.09%, respectively. <i>In vitro</i>&#xa0;release results implied that ^SPTM@DOX and ^LPTM@DOX had good pH-responsive performance under acidic tumor environments and excellent controlled-release behaviors due to the introduction of PDA at physiology pH condition. In the cellular experiment, ^SPTM@DOX and ^LPTM@DOX displayed high cytotoxic effect on HeLa and HepG-2 cells in a concentration-dependent manner as compared to free DOX. In addition, apoptosis analysis further confirmed the higher anticancer therapeutic efficacy of ^SPTM@DOX and ^LPTM@DOX on HeLa and HepG-2 cells. Based on these findings, the trimetallic MOF nanocarriers have a prospective application in cancer therapy as a controlled&#xa0;drug delivery system.</p> Graphical abstract <p></p>