Multistage delivery of chemotherapeutic nanoparticles for breast cancer treatment

Adequate drug delivery to tumors is hindered by barriers such as degradation and non-specific distribution. Nested incorporation of drug-containing nanoparticles within mesoporous silicon particles (MSVs), carriers rationally designed to enhance tumor transport, was hypothesized to result in pronounced and sustained antitumor efficacy. Paclitaxel (PTX)-containing poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) polymer micelles were favorably loaded within MSVs, after which drug release was significantly delayed. Antitumor efficacy analyses in mice bearing MDA-MB-468 breast tumors demonstrated significant tumor growth suppression following a single administration. Results highlight effective chemotherapeutic shuttling and site-specific controlled release afforded by MSVs, potentially translating towards improvements in patient outcomes and morbidity.

• Biological barriers hinder adequate drug delivery to tumors, resulting in poor bioavailability and patient morbidity. • A multistage approach was explored, consisting of nanoparticles loaded within discoidal-shaped mesoporous silicon particles. • Paclitaxel polymer micelles loaded into mesoporous particles showed slow, sustained release and increased cargo protection. • Multistage delivery of drugs successfully prevented tumor growth compared to clinical formulations, with less side effects. • Efficacious tumor responses resulted from enhanced transport dynamics (increased vessel margination) and protective effects.