Bioinspired nanovehicle of furoxans-oxaliplatin improves tumoral distribution for chemo-radiotherapy

The spatiotemporal distribution of therapeutic agents in tumors remains an essential challenge of radiationmediated therapy. Herein, we rationally designed a macrophage microvesicle-inspired nanovehicle of nitric oxide donor-oxaliplatin (FO) conjugate (M-PFO), aiming to promote intratumor permeation and distribution profiles for chemo-radiotherapy. FO was responsively released from M-PFO in intracellular acidic environments, and then be activated by glutathione (GSH) into active oxaliplatin and NO molecules in a programmed manner. M-PFO exhibited notable accumulation, permeation and cancer cell accessibility in tumor tissues. Upon radiation, the reactive peroxynitrite species (ONOO-) were largely produced, which could diffuse into regions over 400 mu m away from the tumor vessels and be detectable after 24 h of radiation, thereby exhibiting superior efficacy in improving the spatiotemporal distribution in tumors versus common reactive oxygen species (ROS). Moreover, M-PFO mediated chemo-radiotherapy caused notable inhibition of tumor growth, with an 89.45% inhibition in HT-29 tumor models and a 92.69% suppression in CT-26 tumor models. Therefore, this bioinspired design provides an encouraging platform to improve intratumor spatiotemporal distribution to synergize chemoradiotherapy.

Automated summary

Researchers designed a macrophage microvesicle-inspired nanovehicle to improve the distribution of therapeutic agents in tumors for chemo-radiotherapy. The nanovehicle released an active compound, oxaliplatin, in response to the acidic environment within cancer cells, and was activated by glutathione to produce the reactive species, peroxynitrite. This nanovehicle showed significant accumulation, permeation, and accessibility to cancer cells in tumor tissues, and exhibited superior efficacy in improving the spatiotemporal distribution in tumors compared to common reactive oxygen species. Its use in chemo-radiotherapy led to notable inhibition of tumor growth in animal models.