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

Maya Kaduri, Mor Sela, Shaked Kagan, Maria Poley, Hanan Abumanhal-Masarweh, Patricia Mora-Raimundo, Alberto Ouro, Nitsan Dahan, Dov Hershkovitz, Jeny Shklover, Janna Shainsky-Roitman, Yosef Buganim, Avi Schroeder*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article numbereabj5435
JournalScience advances
Volume7
Issue number41
DOIs
StatePublished - Oct 2021
Externally publishedYes

Funding

FundersFunder number
Horizon 2020 Framework Programme680242

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