Current Advances on Nanomaterials Interfering with Lactate Metabolism for Tumor Therapy

Abstract

Increasing numbers of studies have shown that tumor cells prefer fermentative glycolysis over oxidative phosphorylation to provide a vast amount of energy for fast proliferation even under oxygen‐sufficient conditions. This metabolic alteration not only favors tumor cell progression and metastasis but also increases lactate accumulation in solid tumors. In addition to serving as a byproduct of glycolytic tumor cells, lactate also plays a central role in the construction of acidic and immunosuppressive tumor microenvironment, resulting in therapeutic tolerance. Recently, targeted drug delivery and inherent therapeutic properties of nanomaterials have attracted great attention, and research on modulating lactate metabolism based on nanomaterials to enhance antitumor therapy has exploded. In this review, the advanced tumor therapy strategies based on nanomaterials that interfere with lactate metabolism are discussed, including inhibiting lactate anabolism, promoting lactate catabolism, and disrupting the “lactate shuttle”. Furthermore, recent advances in combining lactate metabolism modulation with other therapies, including chemotherapy, immunotherapy, photothermal therapy, and reactive oxygen species‐related therapies, etc., which have achieved cooperatively enhanced therapeutic outcomes, are summarized. Finally, foreseeable challenges and prospective developments are also reviewed for the future development of this field.

Advanced NIR-II Fluorescence Imaging Technology for Precise Evaluation of Nanomedicine Delivery in Cancer Therapy

“…Therefore, lysosomal degradation and organelle membranes represent significant subcellular barriers to drug delivery. Additionally, the controlled release of multiple therapeutic agents is a critical advantage of nanomedicine, which is vital for achieving optimal outcomes and is not directly related to the amount of payload [40]. Moreover, the efflux of nanomedicine from tumor cells can also impact treatment results [41].…”

Current progress in the regulation of endogenous molecules for enhanced chemodynamic therapy

“… 70 Lactate is considered a metabolic byproduct of glycolysis in tumor cells, leading to elevated tumor acidity. 71 Consequently, lactate metabolism regulation is an alternative strategy for enhancing CDT. 72 Shi's group reported a pH-responsive and self-augmented nanoplatform (defined as FePt@FeO x @TAM-PEG) fabricated by incorporating a core–shell FePt@FeO x nanocatalyst and pH-responsive tamoxifen (TAM) drug in a poly(styrene- co -maleic anhydride) (PSMA) polymer polymeric matrix and further modifying the surface with PEG ( Fig.…”