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Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include 'nanovesicles (NVs)', 'exosome-mimetic (EM)' and 'hybrid exosomes (HEs)', which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine., (© 2021. The Author(s).)

Extracellular vesicles (EVs) are nanoscale natural membrane vesicles released by cells and are involved in intercellular communication. A number of studies have used autologous cancer cell-derived EVs (ACCD-EVs) as nanocarriers for delivery of therapeutics as they may be more efficiently uptaken by the cancer cells themselves. However, they also have been suggested to promote proliferation, survival and metastasis of cancers. Here, we evaluated the targeting efficacy, therapeutic outcome and safety of ACCD-EVs. Overall, superior targeting efficacy and enhanced anticancer efficacy of ACCD-EV-mediated delivery of therapeutics are evidenced. But existing data are insufficient to allow any conclusion about the safety of therapeutic-loaded EVs. A more profound elucidation of the specificity, efficacy and safety will contribute to future translational research of ACCD-EVs.

Targeted drug delivery to the glioblastoma (GBM) overcoming blood–brain barrier (BBB) has been challenging. Exosomes are promising vehicles for brain tumor drug delivery, but the production and purification hinder its application for nanomedicine. Besides, the formation of protein corona (PC) may affect the behaviour of nanocarriers. Here, multifunctional exosomes-mimetics (EM) are developed and decorated with angiopep-2 (Ang) for enhancing GBM drug delivery by manipulating PC. Docetaxel (DTX)-loaded EM with Ang modification (DTX@Ang-EM) show less absorption of serum proteins and phagocytosis by macrophages. Ang-EM show enhanced BBB penetration ability and targeting ability to the GBM. Ang-EM-mediated delivery increase the concentration of DTX in the tumor area. The multifunctional DTX@Ang-EM exhibits significant inhibition effects on orthotopic GBM growth with reduced side effects of the chemotherapeutic. Findings from this study indicate that the developed DTX@Ang-EM provide a new strategy for targeted brain drug delivery and GBM therapy. [ABSTRACT FROM AUTHOR]

Exosomes (Exos) are promising vehicles for brain drug delivery due to nanosize and the ability to breach the blood–brain barrier (BBB). But the low yield of natural exosomes limits its application for nanomedicine. The generation of bioinspired nanovesicles (BNVs) that mimicking Exos is attractive, but there is a lack of comparative evaluation of Exos and BNVs. Here, we perform the first head-to-head comparison study of Exos and BNVs for brain tumor drug delivery. We show that BNVs derived from brain-derived endothelial cells are competent alternative nanocarrier to natural exosomes. The drug-loading capacity of Exos and BNVs are similar, but the yield of BNVs is substantially higher (500-fold) than Exos. Doxorubicin (DOX)-loaded BNVs (BNV/DOX) and DOX-loaded Exos (Exo/DOX) showed similar pharmacokinetic profiles and prolonged circulation od DOX. Despite inconsistent mechanisms, BNV/DOX can across the BBB, and exhibit suppression effects similar to Exo/DOX on the progress of glioblastoma (GBM) in zebrafish and in vivo subcutaneous and orthotopic xenografts mice models, with minimal systemic toxicity. Findings from this head-to-head comparison study indicate that autologous BNVs is a effective alternative of Exos for brain tumor nanomedicine. [Display omitted] • bEnd.3 cells-derived bioinspired nanovesicles (BNVs) by serial extrusion method showed 500-fold higher yield than exosomes. • bEnd.3 cells-derived BNVs and exosomes can breach the blood–brain barrier via different mechanisms. • BNVs and exosomes contain doxorubicin exhibited similar effects on suppression of the progression of glioblastoma in mice. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is highly metastatic with very short survival and increasing mortality rates. Recent advances in therapeutic regimes and other adjuvant therapies improved slightly overall survival of pancreatic cancer, but fighting metastasis has been challenging and is necessary for achieving cure. Nanomedicine, not limited to drug delivery, offers opportunities for targeting cancer metastasis. Research regarding the prevention of metastasis of this malignancy is highly demanded. Herein, we focus on advances of nanomedicine-based strategies for targeting different stages of metastasis, including cancer stem cells, tumor microenvironment, circulating tumor cells and tumor exosomes. A greater emphasis on targeting metastasis of pancreatic cancer using nanomedicine-based strategies provides avenues for improving pancreatic cancer treatment outcomes in the future. Unlabelled Image • Pancreatic cancer is highly metastatic, but nanomedicine offered opportunities for fighting against metastasis. • Targeting cancer stem cells in the first place is important for preventing metastasis spread. • Remodeling the tumor microenvironment is preferable for intratumoral delivery of chemotherapeutics. • Targeting circulating tumor cells is a feasible strategy for preventing metastatic colony formation • Targeting oncogenic exosomes using specific markers may also to prevent metastasis of PDAC [ABSTRACT FROM AUTHOR]