Integration of cascade delivery and tumor hypoxia modulating capacities in core-releasable satellite nanovehicles to enhance tumor chemotherapy

Abstract

Drug nanovehicles owning tumor microenvironment responsive and modulating capacities are highly demanding for effective tumor chemotherapy but still lack of exploration. Here, a kind of core-releasable satellite nanovehicles was rational constructed, which is composed of polydopamine (PDA) cores as photothermal agents and the carrier for small satellite nanoparticles (NPs) and drugs, G5Au NPs as the drug-loading satellites for deep tumor drug delivery and as catalase-like agents for relieving tumor hypoxia, doxorubicin (DOX) as the model chemotherapeutic drug loaded by both PDA and G5Au NPs, and polyethylene glycol (PEG) shells to improve biosafety. The developed drug-loaded nanovehicles (denoted as PDA-G5Au-PEG@DOX) can release G5Au satellites and DOX in stimuli-responsive manners. Thorough drug delivery in solid tumor can be realized via transporting DOX to the near-by area of and remote area from blood vessels by PDA and G5Au, respectively. Monitored by photoacoustic imaging and near-infrared fluorescence imaging, these PDA-G5Au-PEG@DOX NPs could accumulate in 4T1 tumor effectively. Under this guidance, significant tumor growth suppression could be achieved by the treatment of PDA-G5Au-PEG@DOX NPs plus laser without detectable side effects during the treatment period. The developed drug-loaded core-satellite nanovehicles with tumor microenvironment responsive/modulating capacities are of great potential in precise tumor treatments.

Keywords: Cascade delivery; Deep penetration; Enhanced tumor chemotherapy; Stimuli-responsive; Tumor hypoxia modulating.