Metabolic reprogramming is an important hallmark of malignant cancers, and it’s of great potential to develop anti-cancer strategies targeting metabolic vulnerability of cancer cells [1]. However, the therapeutic efficacy of existing metabolism-regulating agents is often compromised due to tolerance resulting from tumor metabolic plasticity, as well as their poor bioavailability and tumor-targetability [2]. The development of bionanotechnology provides the possibility to solve the above problems. Furthermore, poor drug penetration into solid tumors is another challenging issue in cancer therapy. Through rational structural design, our group has successfully developed a series of biomedical polymeric materials to integrate both functions of promoting drug penetration and regulating tumor metabolism. Particularly, a novel peptide-based dendritic polymer with a multidentate three-dimensional and optimized rigid-flexible structure has been identified, which promotes biomaterials-aided drug penetration into triple-negative breast cancer (TNBC) through vesicle transport [3]. In addition, nanomedicines based on these polymers can intervene tumor cellular metabolic pathways, and particularly, their modulation of the tumor energy metabolism can enhance anti-tumor immune response, contributing to a highly efficacious TNBC treatment [4]. 

Figure 1. Peptide dendritic polymers-based nanomedicines facilitate drug penetration into solid tumors through vesicle transport and regulate metabolism of tumor cells. 

Acknowledgments: This work was financially supported by the National Natural Science Foundation of China (32271445, 52073193). 

References:
[1] Kanarek, N.; Petrova, B.; Sabatini, D. M. Nature, 2020, 579, 507.
[2] Yap, T. A.; Daver, N.; Mahendra, M.; et al. Nature Medicine, 2023, 29, 115.
[3] Gu, L.; Duan, Z.; Chen, X.; et al. Advanced Materials, 2022, 34, 2200048.
[4] Hou, X.; Pan, D.; Zhong, D.; et al. Advanced Materials, 2024, 36, 202400582.