Exosomes as smart drug delivery vehicles for cancer immunotherapy

Zhang, Huan; Wang, Simiao; Sun, Man; Cui, Yongjie; Xing, Jianming; Teng, Lesheng; Xi, Zhifang; Yang, Zhaogang

doi:10.3389/fimmu.2022.1093607

Cited by 33 publications

(19 citation statements)

References 197 publications

(242 reference statements)

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“…The optimal hydrogel H1 was used for its superior biocompatibility and rheological properties to demonstrate the ability to carry and release therapeutics agents. Exosomes have been widely used in the treatment of various diseases due to their excellent biocompatibility, low toxicity, and low immunogenicity (63). In this study, Mens-exo was used as a model drug that demonstrated the potential of the optimal hydrogel for therapeutic agents delivery.…”

Section: Discussionmentioning

confidence: 99%

Design and optimization of thermosensitive injectable alginate-based hydrogels: potential for loading therapeutic compounds

Hasannejad

Arab

Farahmand

et al. 2023

Preprint

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Injectable hydrogels with high biocompatibility and easy fabrication have numerous advantages over other drug delivery systems. These can be readily injected at the tumor site, causing high loads of drugs entrapped within their structures. The aim of the present study, therefore, was to prepare an optimal formulation of alginate-based hydrogels to be thermosensitive and injectable for loading therapeutic agents and drug delivery. Here, four constituents including hydroxypropyl methylcellulose (HPMC), sodium alginate (SA), beta-glycerol phosphate (β-GP), and calcium chloride (CaCl2) were used to obtain the optimal formulations. A surface response methodology (RSM), namely Box-Behnken, in the design of experiment (DOE), was employed. DOE identified 27 hydrogels, which were synthesized accordingly. Based on the gelation temperature (as an objective function), two optimal hydrogel formulations were predicted by DOE and prepared for further analysis. Rheological tests, ART-FTIR, FE-SEM, biodegradability, swelling (at PH = 7.45 and PH = 6.5), and hydrogel biocompatibility to L929 cells (staining of Dihydroetidium (DHE), Phaloidine, and Acridine Orange (AO)) were performed. Furthermore, to demonstrate the potential of the optimum hydrogels for carrying and releasing therapeutic agents, menstrual blood-derived mesenchymal stem cells exosomes (Mens-exo) were used as a model drug, and their release rate and hydrogel degradability were evaluated. The results showed that all the constituents in the hydrogels except for HPMC had significant effects on the gelling process (temperature). The two hydrogel formulations with gelling temperatures of 35° C (H1) and 37° C (H2) were selected for relevant tests. ATR-FTIR and FE-SEM analyses indicated the suitability of chemical and morphological characteristics of both hydrogel samples. The obtained storage modulus (G ') and loss modulus (G″) for gelling temperature and time, strain and frequency tests showed that H1 hydrogel has more favorable rheological properties. Furthermore, in the evaluation of degradability at PH = 6.5, H1 hydrogel was degraded in a longer time (154 hours) and was more stable than H2 (100 hours). The cells loaded in the hydrogels also indicated the superior biocompatibility of H1 hydrogel rather than the H2. Moreover, the Mens-exo loading in H1 hydrogel exhibited a sustained release with reasonable degradability of the hydrogel. The results showed that the optimal hydrogels made up of HPMC, SA, β-GP, and CaCl2 were thermosensitive and injectable. In particular, the H1 hydrogel (SA = 0.889, HPMC = 2, β-GP = 5 and CaCl2 = 3.306) had high potential for loading therapeutic compounds.

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Section: Discussionmentioning

confidence: 99%

Design and optimization of thermosensitive injectable alginate-based hydrogels: potential for loading therapeutic compounds

Hasannejad

Arab

Farahmand

et al. 2023

Preprint

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“…37 The TME is important for tumor proliferation, invasion and metastasis, as well as influencing treatment outcome. 38 It depends on the tumor cell collusion with its surrounding environment. 39 The microenvironment around the tumor includes innate and adaptive immune cells, which express a variety of cytokines that interact with cancer cells.…”

Section: Tumor Immune Escapementioning

confidence: 99%

Immunotherapy: cancer immunotherapy and its combination with nanomaterials and other therapies

Guo¹,

Gao²,

Ahmed³

et al. 2023

J. Mater. Chem. B

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“…[71] This is especially relevant for immunotherapy, where the precise delivery of therapeutic agents to specific cells is critical. [72,73] One of the key advantages of this delivery technique is its specificity. EVs can be engineered to carry specific immunotherapeutic agents and to target specific cells, [74] reducing off-target effects and improving the efficacy of the therapy (see Figure 1C).…”

Section: M3: Ev-based Membrane Fusionmentioning

confidence: 99%

From Theory to Therapy: The Advancements of Extracellular Vesicles in Immunotherapy

Piernitzki,

Staufer

2023

Advanced Therapeutics

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Extracellular vesicles (EVs) are lipid‐membrane‐enclosed particles released from cells, playing a pivotal role in cellular communication, particularly within the immune system. The fundamental molecular mechanisms through which EVs offer unique functionality for immunotherapeutic benefits are identified and reviewed. The focus is on three essential features, all rooted in the EV lipid membrane: immune receptor–ligand interactions at the EV membrane interface, the shielding of immunogenic cargo within the EVs, and the fusion of EVs with target cell membranes for direct cargo delivery. From this, how these distinct EV attributes, from their initial description and analysis in immune communication, have led to the development of novel immunotherapeutic strategies is traced. This review delves into how these strategies are applied in various immunotherapies, such as cancer immunotherapy, autoimmune diseases, infections, vaccinations, and graft‐versus‐host diseases, to modulate communication among different cell types for immune regulation. It is concluded by reviewing clinical trials involving EVs in immunotherapy that have effectively harnessed EVs' unique molecular mechanisms in clinical settings. Research and standardization efforts to maximize the potential impact of EVs on immunotherapy are further suggested.

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Exosomes as smart drug delivery vehicles for cancer immunotherapy

Cited by 33 publications

References 197 publications

Design and optimization of thermosensitive injectable alginate-based hydrogels: potential for loading therapeutic compounds

Design and optimization of thermosensitive injectable alginate-based hydrogels: potential for loading therapeutic compounds

Immunotherapy: cancer immunotherapy and its combination with nanomaterials and other therapies

From Theory to Therapy: The Advancements of Extracellular Vesicles in Immunotherapy

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