Extracellular vesicles (EVs) can mediate intercellular communication by transferring cargo proteins and nucleic acids between cells. The pathophysiological roles and clinical value of EVs are under intense investigation, yet most studies are limited by technical challenges in the isolation of nanoscale EVs (nEVs). Here, we report a lipid nanoprobe that enables spontaneous labelling and magnetic enrichment of nEVs in 15 minutes, with isolation efficiency and cargo composition similar to what can be achieved by the much slower and bulkier method of ultracentrifugation. We also show that the lipid nanoprobes, which allow for downstream analyses of nucleic acids and proteins, enabled the identification of EGFR and KRAS mutations following nEV isolation from blood plasma from non-small-cell lung-cancer patients. The efficiency and versatility of the lipid nanoprobe opens up opportunities in point-of-care cancer diagnostics.

Mitochondria play a critical role in diverse cellular processes, such as energy production and apoptosis regulation. The mitochondria-targeted drug delivery is becoming a potential novel strategy for overcoming drug resistance in cancer therapy. Herein, we synthesize nature-inspired dopamine-derived polydopamine (PDA) nanoparticles. Using triphenylphosphonium (TPP) as the mitochondrial penetration molecule to improve the target efficiency, we synthesize poly(ethylene glycol) (PEG)-modified PDA (PDA-PEG) and TPP-functionalized PEG-modified PDA (PDA-PEG-TPP) nanoparticles. Then anticancer drug doxorubicin (DOX) was loaded on PDA-PEG and PDA-PEG-TPP (PDA-PEG-DOX and PDA-PEG-TPP-DOX) nanoparticles, which are apt to deliver DOX to cell nuclei and mitochondria, respectively. To mimic the repeated anticancer drug treatment in clinical cases, we repeatedly treated the MDA-MD-231 cancer cells for a long time using DOX-loaded nanoparticles and find that the mitochondria targeting PDA-PEG-TPP-DOX has higher potential to overcome the drug resistance than the regular delivery nanoparticles PDA-PEG-DOX. These results indicate the promising potential of applying PDA-PEG-TPP-DOX nanoparticles in mitochondria-targeted drug delivery to overcome the drug resistance in long-time anticancer chemotherapy.

The application of engineered bacteria-based drug delivery vehicles to treat cancer has been practiced for more than a century. Mitochondria, evolutionarily originated from bacteria, are ubiquitous, semi-autonomous cellular organelles. In this study, we present the first exploration of using mitochondria as a delivery system of carbon quantum dots (CQDs) for in vivo imaging and administration of the anticancer drug doxorubicin (DOX). The results show that mitochondria as carriers are compatible with CQD loading and preserve the optical properties of CQDs. Moreover, the mitochondria delivery system can improve the CQD bio-distribution in organs and prolong the retention time of CQDs after intravenous injection. Furthermore, mitochondria loaded with doxorubicin hydrochloride (Mito-DOX) show an enhanced therapeutic effect compared to free DOX. The mitochondria-based "aircraft" system may be a promising novel therapeutic platform with high potential for biological imaging and drug delivery to fight cancer and other diseases.