Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy

TLDR

Developing biomimetic nanoparticles that preserve protein integrity is a major challenge in cancer chemotherapy. The study develops biocompatible tumor‑cell‑exocytosed exosome‑biomimetic porous silicon nanoparticles as targeted drug carriers for cancer chemotherapy. DOX‑loaded exosome‑sheathed porous silicon nanoparticles, produced by tumor‑cell exocytosis, show enhanced tumor accumulation, vascular extravasation, and deep parenchymal penetration after intravenous injection. DOX@E‑PSiNPs demonstrate high cellular uptake, cytotoxicity against bulk cancer cells and CSCs, and in vivo enrichment leading to anticancer activity and CSC reduction in subcutaneous, orthotopic, and metastatic tumor models, proving their potential as efficient chemotherapy carriers.

Abstract

Developing biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy. Here, we develop a biocompatible tumor-cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs) as drug carrier for targeted cancer chemotherapy. Exosome-sheathed doxorubicin-loaded PSiNPs (DOX@E-PSiNPs), generated by exocytosis of the endocytosed DOX-loaded PSiNPs from tumor cells, exhibit enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma following intravenous administration. In addition, DOX@E-PSiNPs, regardless of their origin, possess significant cellular uptake and cytotoxicity in both bulk cancer cells and cancer stem cells (CSCs). These properties endow DOX@E-PSiNPs with great in vivo enrichment in total tumor cells and side population cells with features of CSCs, resulting in anticancer activity and CSCs reduction in subcutaneous, orthotopic and metastatic tumor models. These results provide a proof-of-concept for the use of exosome-biomimetic nanoparticles exocytosed from tumor cells as a promising drug carrier for efficient cancer chemotherapy.