Targeting neurons in the tumor microenvironment with bupivacaine nanoparticles reduces breast cancer progression and metastases

Neurons within the tumor microenvironment promote cancer progression; thus, their local targeting has potential clinical benefits. We designed PEGylated lipid nanoparticles loaded with a non-opioid analgesic, bupivacaine, to target neurons within breast cancer tumors and suppress nerve-to-cancer cross-talk. In vitro, 100-nm nanoparticles were taken up readily by primary neurons, trafficking from the neuronal body and along the axons. We demonstrate that signaling between triple-negative breast cancer cells (4T1) and neurons involves secretion of cytokines stimulating neurite outgrowth. Reciprocally, neurons stimulated 4T1 proliferation, migration, and survival through secretion of neurotransmitters. Bupivacaine curbs neurite growth and signaling with cancer cells, inhibiting cancer cell viability. In vivo, bupivacaine-loaded nanoparticles intravenously administered suppressed neurons in orthotopic triple-negative breast cancer tumors, inhibiting tumor growth and metastatic dissemination. Overall, our findings suggest that reducing nerve involvement in tumors is important for treating cancer.

Automated summary

Neurons within the tumor microenvironment play a role in promoting cancer progression, making local targeting of neurons potentially beneficial in clinical applications. Utilizing PEGylated lipid nanoparticles loaded with bupivacaine, researchers were able to suppress nerve-to-cancer cross-talk and inhibit cancer cell viability by curbing neurite growth and signaling in breast cancer tumors. The findings suggest that reducing nerve involvement in tumors is crucial for effective cancer treatment.