Effective ropivacaine delivery using lipid nanoparticles enables simultaneous cancer therapy and pain control

Cancer and its associated pain pose a serious threat to human health. Cancer therapy and pain management are two distinct medical disciplines and recently proposed cancer neuroscience offers a possibility to simultaneous cancer therapy and pain control. Ropivacaine (Rop), a representative local anesthetic possessing both analgesic and anti-tumor properties, emerges as an ideal agent to achieve this dual objective; however, its therapeutic potency is limited under conventional administration. Herein, a lipid nanoparticles (LNPs)-based Rop delivery system is developed to enhance its in vivo performance. Results show that obtained Rop-loaded LNPs (LNPs/Rop) are of a high drug loading efficiency (86.2 ± 5.5%), leading to a high loading capacity (17.7 ± 0.9%). The hydrodynamic diameter of LNPs/Rop is 171.1 ± 8.3 nm with negatively charged surface (-26.6 ± 2.7 mV). In vitro release assay reveals that LNPs/Rop have a high structural stability, sustainedly releasing 36.7 ± 1.7% of payload within 24 h. Cell experiments indicate that the anti-tumor potency of Rop can be significantly augmented under the co-cultured condition of neuron and tumor cells. In vivo results demonstrate that LNPs/Rop facilitate drug accumulation to target sites-dorsal root ganglion (DRG), spinal cord, and tumor. The accumulated LNPs/Rop in the nervous system effectively relieve cancer pain by blocking pain signal transduction and significantly extends the duration of action to at least 36 h, while it is less than 6 h for free Rop. Meanwhile, LNPs/Rop at a safe dose (3 mg/kg) show comparable anti-tumor potency to an equivalent dose of doxorubicin-loaded LNPs by blocking the nerve-tumor crosstalk. This work highlights a promising strategy to overcome the disconnect between cancer therapy and pain control.