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.

Highlights

  • Developing biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy

  • Luminescent porous silicon nanoparticles (PSiNPs) were prepared by electrochemical etching of silicon wafers, lift-off of PSi film, ultrasonication, centrifugation and activation of luminescence by heating in an aqueous solution

  • The hydrodynamic diameter of PSiNPs was ca. 150 nm measured by dynamic light scattering (DLS, Supplementary Fig. 1a)

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Summary

Introduction

Developing biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy. We develop a biocompatible tumor-cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs) as drug carrier for targeted cancer chemotherapy. 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. DOX@E-PSiNPs exhibit enhanced tumor accumulation, extravasation from blood vessels and deep penetration into tumor parenchyma These features of DOX@E-PSiNPs result in their greater in vivo enrichment in total tumor cells and side population cells with characteristics of CSCs33,34, generating remarkable anticancer and CSCs killing activity in subcutaneous, orthotopic and metastatic tumors (Fig. 1b). Our study provides a approach for cancer therapy by using exosome-biomimetic nanoparticles exocytosed from tumor cells as drug carriers to efficiently deliver anticancer drug

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