Umbilical Cord Blood-Derived M1 Macrophage Exosomes Loaded with Cisplatin Target Ovarian Cancer In Vivo and Reverse Cisplatin Resistance
Xiaohui Zhang,
Jiapo Wang,
Na Liu
et al.
Abstract:We investigated the therapeutic efficacy of umbilical cord blood (UCB)-derived M1 macrophage exosomes loaded with cisplatin (CIS) in ovarian cancer and platinum resistance. M1 macrophages were purified by using CD14 magnetic beads and characterized by flow cytometry. Our analyses included morphology, particle size, particle concentration, potential, drug loading capacity, counts of entry into cells, antitumor effect in vivo, and the ability to reverse drug resistance. A2780, SKOV3, and A2780/ DDP, SKOV3/DDP ov… Show more
“…Animal models, such as mice and rats, possess similar physiologies to humans and are generally cost-effective and easily managed. Usually, researchers administer drug-loaded exosomes into these testing animals, then they monitor the biodistribution of the drug-loaded exosomes and observe the effects on the animals, including physiological and behavioral changes as well as histological effects [ 104 – 107 ]. The use of small animal models thus allows for controlled evaluation of drug-loaded exosomes before advancing to human testing.…”
Section: Assessment Of Drug Encapsulation In Exosomesmentioning
confidence: 99%
“…While in vivo animal models enable examination of the biodistribution, pharmacokinetics, tumor accumulation, and anti-tumor efficacy of the drug-loaded exosomes. Additionally, the toxicity of exosome-loaded drugs is also monitored through changes in body weight, blood counts, biochemistry, and histopathology [ 82 , 104 , 111 ]. Fig.…”
Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies.
Graphical Abstract
“…Animal models, such as mice and rats, possess similar physiologies to humans and are generally cost-effective and easily managed. Usually, researchers administer drug-loaded exosomes into these testing animals, then they monitor the biodistribution of the drug-loaded exosomes and observe the effects on the animals, including physiological and behavioral changes as well as histological effects [ 104 – 107 ]. The use of small animal models thus allows for controlled evaluation of drug-loaded exosomes before advancing to human testing.…”
Section: Assessment Of Drug Encapsulation In Exosomesmentioning
confidence: 99%
“…While in vivo animal models enable examination of the biodistribution, pharmacokinetics, tumor accumulation, and anti-tumor efficacy of the drug-loaded exosomes. Additionally, the toxicity of exosome-loaded drugs is also monitored through changes in body weight, blood counts, biochemistry, and histopathology [ 82 , 104 , 111 ]. Fig.…”
Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies.
Graphical Abstract
“…A recent study based on umbilical cord blood-derived M1 macrophage exosomes demonstrated their ability to inhibit platinum resistance in OC by loading DDP. In addition, this exosome carries lncRNA H19, which is involved in the reversal of DDP chemoresistance ( Figure 3D ) ( 176 ). This innovative approach could hold promise for the treatment of OC.…”
Section: Clinical Relevance Of Lncrnas In Ocmentioning
Long non-coding RNAs (lncRNAs) are multifunctional and participate in a variety of biological processes and gene regulatory networks. The deregulation of lncRNAs has been extensively implicated in diverse human diseases, especially in cancers. Overwhelming evidence demonstrates that lncRNAs are essential to the pathophysiological processes of ovarian cancer (OC), acting as regulators involved in metastasis, cell death, chemoresistance, and tumor immunity. In this review, we illustrate the expanded functions of lncRNAs in the initiation and progression of OC and elaborate on the signaling pathways in which they pitch. Additionally, the potential clinical applications of lncRNAs as biomarkers in the diagnosis and treatment of OC were emphasized, cementing the bridge of communication between clinical practice and basic research.
“…The therapeutic usefulness of umbilical cord blood-derived M1 macrophage exosomes loaded with cisplatin in ovarian cancer with platinum resistance was investigated by Zhang et al [71]. In addition, M1 macrophage-derived exosomes carried lnRNA H19, implicated in upregulation of PTEN protein and downregulation of miR-130a and Pgp gene.…”
After an initial positive response to chemotherapy, cancer patients often acquire chemoresistance and tumor relapse, which makes cancer one of the most lethal diseases worldwide. Exosomes are essential mediators of cell-to-cell communication by delivering their cargo, such as proteins, RNAs and DNA, from cell to cell. They participate in cancer progression, metastasis, immune response and therapy resistance. Their ability to shuttle between cells makes them efficient drug delivery systems. As drug transporters, they provide novel strategies for cancer therapy by advancing targeted drug therapy and improving the therapeutic effects of anti-cancer medications. In this review, a comprehensive overview of the potential of exosomes as therapeutic agents and targeted molecules in the treatment of cancer patients is given. The current challenges of preparation of exosomes loaded with drugs and delivering them to the recipient tumor cells as well as a consequent exosome-mediated cancer therapy are also discussed.
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