bims-engexo 2024-07-28 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2024–07–28
seven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineering Exosomes for Therapeutic Applications: Decoding Biogenesis, Content Modification, and Cargo Loading Strategies.
Exosomes-based immunotherapy for cancer: Effective components in the naïve and engineered forms.
Engineered Mesenchymal Stromal Cell Exosomes-Loaded Microneedles Improve Corneal Healing after Chemical Injury.
Engineered Exosomes Biopotentiated Hydrogel Promote Hair Follicle Growth via Reprogramming the Perifollicular Microenvironment.
Exosomal ssc-miR-1343 targets FAM131C to regulate porcine epidemic diarrhea virus infection in pigs.
Exosomes Derived from Rejuvenated Stem Cells Inactivate NLRP3 Inflammasome and Pyroptosis of Nucleus Pulposus Cells via the Transfer of Antioxidants.
Extracellular Vesicle Surface Display Enhances the Therapeutic Efficacy and Safety Profile of Cancer Immunotherapy.

Int J Nanomedicine. 2024 ;19 7137-7164

Engineering Exosomes for Therapeutic Applications: Decoding Biogenesis, Content Modification, and Cargo Loading Strategies.

Mehrnoosh Bahadorani, Mahboobeh Nasiri, Kristen Dellinger, Shyam Aravamudhan, Reza Zadegan.

  Exosomes emerge from endosomal invagination and range in size from 30 to 200 nm. Exosomes contain diverse proteins, lipids, and nucleic acids, which can indicate the state of various physiological and pathological processes. Studies have revealed the remarkable clinical potential of exosomes in diagnosing and prognosing multiple diseases, including cancer, cardiovascular disorders, and neurodegenerative conditions. Exosomes also have the potential to be engineered and deliver their cargo to a specific target. However, further advancements are imperative to optimize exosomes' diagnostic and therapeutic capabilities for practical implementation in clinical settings. This review highlights exosomes' diagnostic and therapeutic applications, emphasizing their engineering through simple incubation, biological, and click chemistry techniques. Additionally, the loading of therapeutic agents onto exosomes, utilizing passive and active strategies, and exploring hybrid and artificial exosomes are discussed.

Keywords:  diagnostics; drug delivery; engineered exosomes; exosome; therapeutics

DOI:  https://doi.org/10.2147/IJN.S464249
Int Immunopharmacol. 2024 Jul 22. pii: S1567-5769(24)01177-9. [Epub ahead of print]139 112656

Exosomes-based immunotherapy for cancer: Effective components in the naïve and engineered forms.

Huan Bao, Yun Chen, Youni Zhang, Huanrong Lan, Ketao Jin.

  Today, cancer treatment is one of the main challenges for researchers. The main cause of tumor cell formation is mutations that lead to uncontrolled proliferation and inhibition of apoptosis in malignant cells. Tumor cells also create a microenvironment that can suppress the immune system cells' responses through various methods, including producing soluble factors and cell-to-cell communication. After being produced from tumor cells, exosomes can also affect the functions of other cells in this microenvironment. Various studies have shown that exosomes from different sources, including tumor cells and immune cells, can be used to treat cancers due to their characteristics. Since tumor cells are rich sources of various types of tumor peptides, they can induce anti-tumor responses. Immune cells also produce exosomes that mimic the functions of their cells of origin, such that exosomes derived from NK cells and CTLs can directly lead to their apoptosis after merging with tumor cells. However, many researchers have pointed out that naïve exosomes have a limited therapeutic function, and their therapeutic potential can be increased by manipulating and engineering them. There are various methods to modify exosomes and improve their therapeutic potential. In general, these methods are divided into two parts, which include changing the cell of origin of the exosome and encapsulating the exosome to carry different drugs. In this review, we will discuss the studies on the therapeutic use of naive and engineered exosomes and provide an update on new studies in this field.

Keywords:  Cancer; Drug loading; Exosomes; Immune cells; Treatment; Tumor

DOI:  https://doi.org/10.1016/j.intimp.2024.112656
ACS Nano. 2024 Jul 24.

Engineered Mesenchymal Stromal Cell Exosomes-Loaded Microneedles Improve Corneal Healing after Chemical Injury.

Fei Yu, Xuan Zhao, Qian Wang, Po-Han Fang, Liu Liu, Xinyue Du, Weihua Li, Dalian He, Tingting Zhang, Ying Bai, Lu Liu, Saiqun Li, Jin Yuan.

  Corneal alkali burns represent a prevalent ophthalmic emergency with the potential to induce blindness. The main contributing mechanisms include excessive inflammation and delayed wound healing. Existing clinical therapies have limitations, promoting the exploration of alternative methods that offer improved efficacy and reduced side effects. Adipose-derived stem cell-exosome (ADSC-Exo) has the potential to sustain immune homeostasis and facilitate tissue regeneration. Nevertheless, natural ADSC-Exo lacks disease specificity and exhibits limited bioavailability on the ocular surface. In this study, we conjugated antitumor necrosis factor-α antibodies (aT) to the surface of ADSC-Exo using matrix metalloproteinase-cleavable peptide chains to create engineered aT-Exo with synergistic effects. In both in vivo and in vitro assessments, aT-Exo demonstrated superior efficacy in mitigating corneal injuries compared to aT alone, unmodified exosomes, or aT simply mixed with exosomes. The cleavable conjugation of aT-Exo notably enhanced wound healing and alleviated inflammation more effectively. Simultaneously, we developed poly(vinyl alcohol) microneedles (MNs) for precise and sustained exosome delivery. The in vivo results showcased the superior therapeutic efficiency of MNs compared with conventional topical administration and subconjunctival injection. Therefore, the bioactive nanodrugs-loaded MNs treatment presents a promising strategy for addressing ocular surface diseases.

Keywords:  anti-TNF-α antibodies; corneal alkali injury; engineered exosomes; microneedles; wound healing

DOI:  https://doi.org/10.1021/acsnano.4c00423
Pharmaceutics. 2024 Jul 13. pii: 935. [Epub ahead of print]16(7):

Engineered Exosomes Biopotentiated Hydrogel Promote Hair Follicle Growth via Reprogramming the Perifollicular Microenvironment.

Hairui Zhang, Jiali Yao, Qianyang Jiang, Yurou Shi, Weihong Ge, Xiaoling Xu.

  Androgenetic alopecia (AGA) is a highly prevalent condition in contemporary society. The conventional treatment of minoxidil tincture is hindered by issues such as skin irritation caused by ethanol, non-specific accumulation in hair follicles, and short retention due to its liquid form. Herein, we have developed a novel minoxidil-incorporated engineered exosomes biopotentiated hydrogel (Gel@MNs) that has the capability to modulate the perifollicular microenvironment for the treatment of AGA. Leveraging the exceptional skin penetration abilities of flexible liposomes and the targeting properties of exosomes, the encapsulated minoxidil can be effectively delivered to the hair follicles. In comparison to free minoxidil, Gel@MNs demonstrated accelerated hair regeneration in an AGA mouse model without causing significant skin irritation. This was evidenced by an increase in both the number and size of hair follicles within the dermal layer, enhanced capillary formation surrounding the follicles, and the regulation of the transition of hair follicle cells from the telogen phase to the anagen growth phase. Therefore, this safe and microenvironment-modifying hybrid exosome-embedded hydrogel shows promising potential for clinical treatment of AGA.

Keywords:  androgenetic alopecia; engineered exosomes; flexible liposomes; hair follicle; reprogram the perifollicular microenvironment

DOI:  https://doi.org/10.3390/pharmaceutics16070935
Vet Res. 2024 Jul 22. 55(1): 91

Exosomal ssc-miR-1343 targets FAM131C to regulate porcine epidemic diarrhea virus infection in pigs.

Weiyun Qin, Jing Jiang, Jiayun Wu, Yunxiao Xie, Zhengchang Wu, Mingan Sun, Wenbin Bao.

  The porcine epidemic diarrhea virus (PEDV) causes diarrhea in piglets, thereby causing very significant economic losses for the global swine industry. In previous studies, it has been confirmed that microRNAs (miRNAs) play an important role in the infection caused by PEDV. However, the precise molecular mechanism of miRNAs in the regulation of PEDV infection is still not fully understood. In the present study, we utilized miRNA-seq analysis to identify ssc-miR-1343 with differential expression between PEDV-infected and normal piglets. The expression of ssc-miR-1343 was detected in isolated exosomes, and it was found to be significantly higher than that in the controls following PEDV infection. The ssc-miR-1343 mimic was found to decrease PEDV replication, whereas the ssc-miR-1343 inhibitor was observed to increase PEDV replication, and ssc-miR-1343 was delivered by exosomes during PEDV infection. Mechanistically, ssc-miR-1343 binds to the 3'UTR region of FAM131C, down-regulating its expression, and FAM131C has been shown to enhance PEDV replication through simultaneously suppressing pathways associated with innate immunity. The ssc-miR-1343/FAM131C axis was found to upregulate the host immune response against PEDV infection. In conclusion, our findings indicate that the transport of ssc-miR-1343 in exosomes is involved in PEDV infection. This discovery presents a new potential target for the development of drugs to treat PEDV.

Keywords:  FAM131C; Pigs; Ssc-miR-1343; exosomes; immune response; porcine epidemic diarrhea virus

DOI:  https://doi.org/10.1186/s13567-024-01345-3
Tissue Eng Regen Med. 2024 Jul 26.

Exosomes Derived from Rejuvenated Stem Cells Inactivate NLRP3 Inflammasome and Pyroptosis of Nucleus Pulposus Cells via the Transfer of Antioxidants.

Shuai Peng, Xiangyang Liu, Lei Chang, Bin Liu, Mingyan Zhang, Yan Mao, Xiongjie Shen.

   BACKGROUND: Accumulating evidence supports the potential of exosomes as a promising therapeutic approach for intervertebral disc degeneration (IDD). Nevertheless, enhancing the efficiency of exosome treatment remains an urgent concern. This study investigated the impact of quercetin on the characteristics of mesenchymal stem cells (MSCs) and their released exosomes.
METHODS: Exosomes were obtained from quercetin pre-treated MSCs and quantified for the production based on nanoparticle tracking and western blot analysis. The molecules involved in the secretion and cargo sorting of exosomes were investigated using western blot and immunofluorescence analysis. Based on the in vitro biological analysis and in vivo histological analysis, the effects of exosomes derived from conventional or quercetin-treated MSCs on nucleus pulposus (NP) cells were compared.
RESULTS: A significant enhancement in the production and transportation efficiency of exosomes was observed in quercetin-treated MSCs. Moreover, the exosomes derived from quercetin-treated MSCs exhibited a greater abundance of antioxidant proteins, specifically superoxide dismutase 1 (SOD1), which inhibit the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome in NP cells. Through in vitro and in vivo experiments, it was elucidated that exosomes derived from quercetin-treated MSCs possessed enhanced anti-inflammatory and antioxidant properties.
CONCLUSION: Collectively, our research underscores an optimized therapeutic strategy for IDD utilizing MSC-derived exosomes, thereby augmenting the efficacy of exosomes in intervertebral disc regeneration.

Keywords:  Exosomes; Intervertebral disc degeneration; Mesenchymal stem cells; Quercetin

DOI:  https://doi.org/10.1007/s13770-024-00663-z
Mol Ther. 2024 Jul 19. pii: S1525-0016(24)00468-4. [Epub ahead of print]

Extracellular Vesicle Surface Display Enhances the Therapeutic Efficacy and Safety Profile of Cancer Immunotherapy.

Migara Kavishka Jayasinghe, Yock Sin Lay, Dawn Liu Xiao Tian, Chang Yu Lee, Chang Gao, Brendon Zhi Jie Yeo, Faith Yuan Xin How, Rebecca Carissa Prajogo, Dong Van Hoang, Hong Anh Le, Thach Tuan Pham, Boya Peng, Cao Dai Phung, Daniel G Tenen, Minh T N Le.

  Immunotherapy has emerged as a mainstay in cancer therapy, yet its efficacy is constrained by the risk of immune-related adverse events. In this study, we present a nanoparticle-based delivery system that enhances the therapeutic efficacy of immunomodulatory ligands while concurrently limiting systemic toxicity. We demonstrate that extracellular vesicles (EVs), lipid bilayer enclosed particles released by cells, can be efficiently engineered via iEDDA-mediated conjugation to display multiple immunomodulatory ligands on their surface. Display of immunomodulatory ligands on the EV surface conferred substantial enhancements in signaling efficacy, particularly for tumor necrosis factor receptor superfamily (TNFRSF) agonists, where EV surface display served as an alternative FcγR-independent approach to induce ligand multimerization and efficient receptor crosslinking. EVs displaying a complementary combination of immunotherapeutic ligands were able to shift the tumor immune milieu towards an anti-tumorigenic phenotype and significantly suppress tumor burden and increase survival in multiple models of metastatic cancer to a greater extent than an equivalent dose of free ligands. In summary, we present an EV-based delivery platform for cancer immunotherapeutic ligands that facilitates superior anti-tumor responses at significantly lower doses with less side-effects than is possible with conventional delivery approaches.

Keywords:  cancer immunotherapy; extracellular vesicles; iEDDA; nanomedicine; surface functionalization

DOI:  https://doi.org/10.1016/j.ymthe.2024.07.013