Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy

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.

Cell Membrane Nanotherapeutics: From Synthesis to Applications Emerging Tools for Personalized Cancer Therapy

“…In order to preserve the intrinsic properties of the exosome membrane, a new a technique was devised by exploiting exocytosis to camouflage DOX loaded luminescent porous silicon nanoparticles with exosomes using Bel7402 cancer cells. [ 70 ] Exosome camouflaged nanoparticles had enhanced tumor accumulation, and this resulted in excellent anticancer activity. Strikingly, the size of resultant nanoparticles loaded with DOX remained same even when incubated in PBS with 10% fatal bovine serum up to 6 days.…”

“…Exosomes can be good alternative to cell membrane coating due to their high tumor targeting ability. Coupling exosome exocytosis machinery with nanoparticles endosomal machinery [ 70 ] can enable using cells as a factory to continuously obtain coated nanoparticles without destructing the cells. Extraction and isolation yield are needed to be further improved for exosome coating nanotechnology to achieve its full potential.…”

Microcellular Environmental Regulation of Silver Nanoparticles in Cancer Therapy: A Critical Review

“…Their combined effects have been exploited for the delivery of cytochrome C into the cytosol which can initiate the activation of caspase 3 and caspase 9, leading to apoptosis [21,38]. Herein, we have detailed the redox activity of AgNPs as well as their role in cytotoxicity/genotoxicity-induced programed cell death and, subsequently, their utilization as a targeted therapy against tumor proliferation [39][40][41][42]. The summary of molecular effects, risk classification, and physiochemical properties of AgNPs are summarized in Table 1.…”

Exosomes as a Source of Cancer Biomarkers: Advances in Electrochemical Biosensing of Exosomes

“…Nanotechnology will probably also play an important role in many exosome‐based technologies focusing on diagnostics and therapy, since some exosome properties enhance the biocompatibility and cellular uptake of drug nanocarriers. Exosome‐sheathed and doxorubicin‐loaded porous silicon NPs were generated by the exocytosis of endocytosed doxorubicin‐loaded NPs from tumour cells and were subsequently used to investigate their tumour accumulation, blood vessel extravasation, tumour penetration and cytotoxicity, which are important features for in vivo applications of these biomimetics . Magnetic nanoparticles (MNPs), on the other hand, afford the possibility to selectively isolate the desired exosomal fraction from a sample, as in the case of anti‐CD63 antibody‐modified MNPs and human liver cancer cells HepG2.…”