Engineering lactate-modulating nanomedicines for cancer therapy

Lactate in tumors has long been considered metabolic junk derived from the glycolysis of cancer cells and utilized only as a biomarker of malignancy, but is presently believed to be a pivotal regulator of tumor development, maintenance and metastasis. Indeed, tumor lactate can be a fuel for energy supply and functions as a signaling molecule, which actively contributes to tumor progression, angiogenesis, immunosuppression, therapeutic resistance, etc., thus providing promising opportunities for cancer treatment. However, the current approaches for regulating lactate homeostasis with available agents are still challenging, which is mainly due to the short half-life, low bioavailability and poor specificity of these agents and their unsatisfactory therapeutic outcomes. In recent years, lactate modulation nanomedicines have emerged as a charming and efficient strategy for fighting cancer, which play important roles in optimizing the delivery of lactate-modulating agents for more precise and effective modulation and treatment. Integrating specific lactate-modulating functions in diverse therapeutic nanomedicines may overcome the intrinsic restrictions of different therapeutic modalities by remodeling the pathological microenvironment for achieving enhanced cancer therapy. In this review, the most recent advances in the engineering of functional nanomedicines that can modulate tumor lactate for cancer therapy are summarized and discussed, and the fundamental mechanisms by which lactate modulation benefits various therapeutics are elucidated. Finally, the challenges and perspectives of this emerging strategy in the anti-tumor field are highlighted.

Automated summary

Lactate in tumors is now recognized as a pivotal regulator of tumor development, maintenance, and metastasis, serving as both an energy fuel and a signaling molecule. Modulating lactate in tumors has promising opportunities for cancer treatment, but current approaches face challenges due to limitations such as low bioavailability. Nanomedicines that can modulate tumor lactate have emerged as an efficient strategy, enabling precise and effective modulation and treatment for enhanced cancer therapy. The recent advances and mechanisms of lactate modulation nanomedicines in cancer therapy are discussed in this review, along with the challenges and perspectives of this emerging strategy.