Platelets are highly efficient and efficacious carriers for tumor-targeted nano-drug delivery

Li, Qi‐Rui; Xu, Hua‐Zhen; Xiao, Rong-Cheng; Yan, Liu; Tang, Jun‐Ming; Li, Jian; Yu, Tingting; Liu, Bin; Li, Liu‐Gen; Wang, Meifang; Han, Ning; Xu, Yunyun; Wang, Chao; Komatsu, Naoki; Zhao, Li; Peng, Xing‐Chun; Li, Tong‐Fei; Chen, Xiao

doi:10.1080/10717544.2022.2053762

Cited by 27 publications

(17 citation statements)

References 40 publications

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“…PMVs are a type of cell membrane that itself has a potential camouflage effect that allows it to escape immunogenic monitoring, with low systemic cytotoxicity, to extend blood circulation [12][13][14]. Platelet-mediated delivery of tumor-targeted drugs is currently a popular topic of research, including the use of platelets to target lymphoma with platelet-encapsulated DOX, which enhanced the inhibition of Raji cell growth and reduced the toxicity of DOX to the heart [15,16]. However, in addition to research in tumor targeting, furthermore, other types of diseases, such as hematological disorders and cardiovascular and cerebrovascular diseases, can be targeted through the platelet membrane delivery of drugs or binding molecules [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Platelet-Membrane-Encapsulated Carvedilol with Improved Targeting Ability for Relieving Myocardial Ischemia–Reperfusion Injury

et al. 2022

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In recent years, cell membrane drug delivery systems have received increasing attention. However, drug-loaded membrane delivery systems targeting therapy in myocardial ischemia–reperfusion injury (MIRI) have been relatively rarely studied. The purpose of this study was to explore the protective effect of platelet-membrane-encapsulated Carvedilol on MIRI. We extracted platelets from the blood of adult SD rats and prepared platelet membrane vesicles (PMVs). Carvedilol, a nonselective β-blocker, was encapsulated into the PMVs. In order to determine the best encapsulation rate and drug-loading rate, three different concentrations of Carvedilol in low, medium, and high amounts were fused to the PMVs in different volume ratios (drugs/PMVs at 2:1, 1:1, 1:2, and 4:1) for determining the optimum concentration and volume ratio. By comparing other delivery methods, including abdominal injection and intravenous administration, the efficacy of PMVs-encapsulated drug-targeted delivery treatment was observed. The PMVs have the ability to target ischemic-damaged myocardial tissue, and the concentration and volume ratio at the optimum encapsulation rate and the drug-loading rate are 0.5 mg and 1:1. We verified that PMVs@Carvedilol had better therapeutic effects compared to other treatment groups, and immunofluorescence observation showed a significant improvement in the apoptosis indicators and infarction area of myocardial cells. Targeted administration of PMVs@Carvedilol may be a promising treatment for myocardial reperfusion injury, as it significantly improves postinjury cardiac function and increases drug utilization compared to other delivery methods.

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Section: Introductionmentioning

confidence: 99%

Platelet-Membrane-Encapsulated Carvedilol with Improved Targeting Ability for Relieving Myocardial Ischemia–Reperfusion Injury

et al. 2022

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“…Platelets can also deliver microRNAs to tumor cells 61 and nearby immune cells 62 . Engineered platelets can be efficient and efficacious in suppressing tumor proliferation 63 . Overall, the determination of key factors in platelets that mediate TAMs is important for tumor treatment.…”

Section: Discussionmentioning

confidence: 99%

Platelets promote CRC by activating the C5a/C5aR1 axis via PSGL-1/JNK/STAT1 signaling in tumor-associated macrophages

Chen¹,

Gong²,

Zhao³

et al. 2023

Theranostics

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Rationale: Platelets can influence the progression and prognosis of colorectal cancer (CRC) through multiple mechanisms, including crosstalk with tumor-associated macrophages (TAMs). However, the mechanisms underlying the crosstalk between platelets and TAMs remain unclear. The present study aimed to investigate the role of intratumoral platelets in regulating the function of TAMs and to identify the underlying mechanisms. Methods: The interaction of platelets with macrophages was assessed in the presence or absence of the indicated compounds in vivo . An azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC mouse model was used to investigate the role of platelets in controlling CRC development. Multiplexed immunofluorescence staining, fluorescence-activated cell sorting (FACS), and RNA sequence analysis were used to examine the changes in TAMs. TAMs and bone marrow-derived macrophages (BMDMs) were treated with the indicated compounds or siRNA against specific targets, and the expression levels of signal transducer and activator of transcription 1 (STAT1), c-Jun N-terminal kinase (JNK), and P-selectin glycoprotein ligand-1 (PSGL-1) were measured by Western blotting. The mRNA expression levels of complement 5 ( C5 ), complement 5a receptor 1 ( C5ar1 ), Arginase 1 ( Arg1 ) and Il10 were measured by real-time RT-PCR, and the complement 5a (C5a) concentration was measured by ELISA. The dual-luciferase reporter assay and ChIP assay were performed to examine the potential regulatory mechanisms of platelet induction of C5 transcription in TAMs. Results: In our study, we found that an increase in platelets exacerbated CRC development, while inhibiting platelet adhesion attenuated tumor growth. Platelets signal TAMs through P-selectin (CD62P) binding to PSGL-1 expressed on TAMs and activating the JNK/STAT1 pathway to induce the transcription of C5 and the release of C5a, shifting TAMs toward a protumor phenotype. Inhibiting the C5a/C5aR1 axis or PSGL-1 significantly reduced CRC growth. Conclusions: An increase in intratumoral platelets promoted CRC growth and metastasis by CD62P binding to PSGL-1 expressed on TAMs, leading to JNK/STAT1 signaling activation, which promoted C5 transcription and activated the C5a/C5aR1 axis in TAMs. Our study examined the mechanism of the crosstalk between platelets and TAMs to exacerbate CRC development and proposed a potential therapeutic strategy for CRC patients.

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“…Subsequently, they further combined this strategy with thermal ablation to achieve remarkably diminished or even cleared tumor recurrence and metastasis. [ 47 ] Except for the insertion or conjugation method for the loading of free drug, drug‐loaded nanoparticles could also be integrated into platelets, including nanocomplex, [ 48 ] nanogels, nanodiamond, [ 49 ] and liposome. [ 50 ]…”

Section: Platelet‐derived Microparticlesmentioning

confidence: 99%

Organism‐Generated Biological Vesicles In Situ: An Emerging Drug Delivery Strategy

2022

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Biological vesicles, containing genetic materials and proteins of the original cells, are usually used for local or systemic communications among cells. Currently, studies on biological vesicles as therapeutic strategies or drug delivery carriers mainly focus on exogenously generated biological vesicles. However, the limitations of yield and purity caused by the complex purification process still hinder their clinical transformation. Recently, it has been reported that living organisms, including cells and bacteria, can produce functional/therapeutic biological vesicles within body automatically. Therefore, using organisms to produce endogenous biological vesicles in body as drug/bio‐information delivery carriers has become a potential therapeutic strategy. In this review, the current development status and application prospects of in situ organism‐produced biological vesicles are introduced. The advantages and effects of this endogenous biological vesicles‐based strategy in drug delivery and disease treatments are analyzed. According to the type of endogenous biological vesicles, they are divided into four categories: exosomes, platelet‐derived microparticles, apoptotic bodies, and bacteria‐released outer membrane vesicles. And finally, the shortcomings of current research and future development are analyzed. This review is believed to open up the application of endogenous biological vesicles in the field of biomedicine and shed light on current research.

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Platelets are highly efficient and efficacious carriers for tumor-targeted nano-drug delivery

Cited by 27 publications

References 40 publications

Platelet-Membrane-Encapsulated Carvedilol with Improved Targeting Ability for Relieving Myocardial Ischemia–Reperfusion Injury

Platelet-Membrane-Encapsulated Carvedilol with Improved Targeting Ability for Relieving Myocardial Ischemia–Reperfusion Injury

Platelets promote CRC by activating the C5a/C5aR1 axis via PSGL-1/JNK/STAT1 signaling in tumor-associated macrophages

Organism‐Generated Biological Vesicles In Situ: An Emerging Drug Delivery Strategy

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