Co‐Delivery of Metabolic Modulators Leads to Simultaneous Lactate Metabolism Inhibition and Intracellular Acidification for Synergistic Cancer Therapy

Abstract Simultaneous lactate metabolism inhibition and intracellular acidification (LIIA) is a promising approach for inducing tumor regression by depleting ATP. However, given the limited efficacy of individual metabolic modulators, a combination of various modulators is required for highly efficient LIIA. Herein, a co‐delivery system that combines lactate transporter inhibitor, glucose oxidase, and O 2 ‐evolving nanoparticles is proposed. As a vehicle, a facile room‐temperature synthetic method for large‐pore mesoporous silica nanoparticles (L‐MSNs) is developed. O 2 ‐evolving nanoparticles are then conjugated onto L‐MSNs, followed by immobilizing the lactate transporter inhibitor and glucose oxidase inside the pores of L‐MSNs. To load the lactate transporter inhibitor, which is too small to be directly loaded into the large pores, it is encapsulated in albumin by controlling the albu…