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.
Synthetic cells are artificial systems capable of replacing malfunctioning cells inside the body. This study describes the development of remotely‐activated synthetic cells and their capacity to ...treat disease. These cell‐sized artificial systems contain all the molecular machinery necessary for transcription and translation, including – ribosomes, RNA polymerase, amino acids and energy. Avi Schroeder and co‐workers present this work in article 1701163. Here, synthetic cells are programmed to produce therapeutic proteins inside tumors, eradicating the surrounding cancer cells.
Protocells, artificial cell-like particles, capable of autonomously synthesizing RNA and proteins based on a DNA template, are emerging platforms for studying cellular functions and for revealing the ...origins-of-life. Here, we show for the first time that artificial lipid-based vesicles, containing the molecular machinery necessary for transcription and translation, can be used to synthesize anti-cancer proteins inside tumors. The particles were engineered as stand-alone systems, sourcing nutrients from their biological microenvironment to trigger protein synthesis. When pre-loaded with template DNA, amino acids and energy-supplying molecules protocells synthesized, up to 2×10
7
copies of superfolder green fluorescent protein (sfGFP) were synthesized in each liposome. A variety of proteins, having molecular weights reaching 66 kDa and with diagnostic and therapeutic activities, were synthesized inside the particles. Incubating protein producing particles, encoded to secrete
Pseudomonas
exotoxin A (PE) with 4T1 breast cancer cells in culture, resulted in killing of most of the malignant cells. In mice bearing 4T1 tumors, histological evaluation of the tumor tissue after a local injection of PE-producing particles, indicating robust apoptosis. Protein producing particles are synthetic-biology platforms capable of synthesizing therapeutic proteins on-demand.
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