M1 macrophage-derived exosomes synergistically enhance the anti- bladder cancer effect of gemcitabine

Tang, Zhenye; Tang, Chenye; Sun, Chun; Ying, Xiangjun; Shen, Ruilin

doi:10.18632/aging.204200

Cited by 20 publications

(5 citation statements)

References 25 publications

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“…In another study, M1-Exo-GEM (pre-loading M1 macrophage-derived exosomes(M1-Exo) with Gemcitabine (GEM) by ultrasound technology) was built up for killing mouse bladder cancer MB49 cells. Compared with M1-Exo and GEM, M1-Exo-GEM had significantly up-regulated the expression of inflammatory cytokines and stronger cytotoxic effect on cancer cells [ 100 ].…”

Section: Other Systemic Diseasesmentioning

confidence: 99%

The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System

Hân

et al. 2022

Pharmaceutics

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Drug delivery system (DDS) realizes the drug delivery process through the drug carrier. As an important part of DDS, the selection of the drug carrier material is extremely critical, which requires the carrier material to possess excellent biocompatibility and targeting and not affect the pharmacological action of the drug. As one of the endogenous extracellular vesicles, exosomes are 30–100 nm in diameter, which are considered a new generation of a natural nanoscale delivery system. Exosomes secreted by different types of cells carry signaling molecules (such as proteins and nucleic acid) playing an important role in cell behaviors. Owing to their ability to specialize in intercellular communication, exosomes provide a distinctive method to deliver therapeutic drugs to target cells. In this concept, exosomes as the natural liposomes carry endogenous biomolecules, have excellent biocompatibility, and could be loaded with cargo both in vivo and in vitro. In addition, modifications by genetic and/or chemical engineering to part of the exosome surface or complement the desired natural effect may enhance the targeting with drug loading capability. Notably, exosomes weakly react with serum proteins prolonging cargo half-life. Overall, exosomes as natural carriers integrate the superiority of synthetic nanocarriers and cellular communication while precluding their limitations, which provides novel and reliable methods for drug delivery and treatment. Our review focuses on the therapeutic potentials and clinical values of exosomes as a carrier of drug delivery system in multiple diseases, including cancer, nervous, immune, and skeletal system diseases.

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Section: Other Systemic Diseasesmentioning

confidence: 99%

The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System

Hân

et al. 2022

Pharmaceutics

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“…Meanwhile, several groups have successfully demonstrated the use of macrophage-derived exosomes to improve therapeutic efficacy and drug delivery for cancer treatments. Tang et al obtained exosomes from M1 phenotype macrophages by treating raw 264.7 cells with LPS and IFN-γ and found that they express higher levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, thereby exacerbating the cytotoxic effects of gemcitabine on mouse bladder cancer [41]. Incorporation of paclitaxel into exosomes derived from raw 264.7 cells could enhance the cytotoxicity by more than 50 times in multi-drug resistant cancer cells with effective tumor site delivery observed in a mouse model of pulmonary metastases [21].…”

Section: Discussionmentioning

confidence: 99%

Exosome-Modified Liposomes Targeted Delivery of Thalidomide to Regulate Treg Cells for Antitumor Immunotherapy

et al. 2023

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Thalidomide (THD), a synthetic derivative of glutamic acid, was initially used as a sedative and antiemetic until the 1960s, when it was found to cause devastating teratogenic effects. However, subsequent studies have clearly demonstrated the anti-inflammatory, anti-angiogenic, and immunomodulatory properties of thalidomide, thus providing a rationale for its current use in the treatment of various autoimmune diseases and cancers. Our group found that thalidomide can suppress the regulatory T cells (Tregs), a minor subset of CD4+ T cells (~10%) with unique immunosuppressive activity that have been shown to accumulate in the tumor microenvironment (TME) and represent a major mechanism of tumor immune evasion. Due to the low solubility of thalidomide in its present form of administration, coupled with its lack of specificity for targeted delivery and controlled drug release, it is an urgent need to find potent delivery methods that can significantly enhance its solubility, optimize the desired site of drug action, and mitigate its toxicity. In this study, the isolated exosomes were incubated with synthetic liposomes to form hybrid exosomes (HEs) that carried THD (HE-THD) with uniform size distribution. The results demonstrated that HE-THD could significantly abrogate the expansion and proliferation of Tregs induced by TNF, and this might result from blocking TNF-TNFR2 interaction. By encapsulating THD in hybrid exosomes, our drug delivery system successfully increased the solubility of THD, laying a foundation for future in vivo experiments that validate the antitumor activity of HE-THD by reducing the Treg frequency within the tumor microenvironment.

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“…In addition, Wang and his group prepared PTX-loaded EXOs isolated from murine macrophages [ 74 ]. In particular, through sequential centrifugations, the EXOs were isolated from lipopolysaccharide-activated M1 macrophages, able to produce EXOs with documented antitumor activity [ 113 ]. PTX was loaded through sonication followed by incubation at 37 °C, to restore the EXO membranes, obtaining a DL of 19%.…”

Section: Plant Derivatives Vehiculated In Exos and Biomimetic Hybrid ...mentioning

confidence: 99%

Phytochemicals and Cancer Treatment: Cell-Derived and Biomimetic Vesicles as Promising Carriers

et al. 2023

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The majority of anticancer agents currently used derive from natural sources: plants, frequently the ones employed in traditional medicines, are an abundant source of mono- and diterpenes, polyphenols, and alkaloids that exert antitumor activity through diverse mechanisms. Unfortunately, many of these molecules are affected by poor pharmacokinetics and limited specificity, shortcomings that may be overcome by incorporating them into nanovehicles. Cell-derived nanovesicles have recently risen to prominence, due to their biocompatibility, low immunogenicity and, above all, targeting properties. However, due to difficult scalability, the industrial production of biologically-derived vesicles and consequent application in clinics is difficult. As an efficient alternative, bioinspired vesicles deriving from the hybridization of cell-derived and artificial membranes have been conceived, revealing high flexibility and appropriate drug delivery ability. In this review, the most recent advances in the application of these vesicles to the targeted delivery of anticancer actives obtained from plants are presented, with specific focus on vehicle manufacture and characterization, and effectiveness evaluation performed through in vitro and in vivo assays. The emerging overall outlook appears promising in terms of efficient drug loading and selective targeting of tumor cells, suggesting further engrossing developments in the future.

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M1 macrophage-derived exosomes synergistically enhance the anti- bladder cancer effect of gemcitabine

Cited by 20 publications

References 25 publications

The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System

The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System

Exosome-Modified Liposomes Targeted Delivery of Thalidomide to Regulate Treg Cells for Antitumor Immunotherapy

Phytochemicals and Cancer Treatment: Cell-Derived and Biomimetic Vesicles as Promising Carriers

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