Fusion of Tumor-Derived Exosomes with Long-Circulating and pH-Sensitive Liposomes Loaded with Doxorubicin for the Treatment of Breast Cancer

Gomes, Eliza Rocha; Carvalho, A. T.; Barbosa, T. C.; Ferreira, L. L.; Calado, Hállen Daniel Rezende; Sabino, A. P.; Oliveira, Mônica Cristina

doi:10.1208/s12249-022-02349-y

Cited by 13 publications

(15 citation statements)

References 32 publications

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“…It is well-known that the antitumor efficacy of pH-sensitive liposomes depends on their ability to release the drug into the tumor region. In an acidic environment, these formulations, composed of DOPE (a fusogenic lipid), can fuse or destabilize, releasing the encapsulated content [ 36 , 37 ]. Herein, the release study was carried out at pH 5.0 and 7.4.…”

Section: Discussionmentioning

confidence: 99%

Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines

et al. 2023

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Doxorubicin (DOX) is a potent chemotherapeutic drug used as the first line in breast cancer treatment; however, cardiotoxicity is the main drawback of the therapy. Preclinical studies evidenced that the association of simvastatin (SIM) with DOX leads to a better prognosis with reduced side effects and deaths. In this work, a novel pH-sensitive liposomal formulation capable of co-encapsulating DOX and SIM at different molar ratios was investigated for its potential in breast tumor treatment. Studies on physicochemical characterization of the liposomal formulations were carried out. The cytotoxic effects of DOX, SIM, and their combinations at different molar ratios (1:1; 1:2 and 2:1), free or co-encapsulated into pH-sensitive liposomes, were evaluated against three human breast cancer cell lines (MDA-MB-231, MCF-7, and SK-BR-3). Experimental protocols included cell viability, combination index, nuclear morphological changes, and migration capacity. The formulations showed a mean diameter of less than 200 nm, with a polydispersity index lower than 0.3. The encapsulation content was ~100% and ~70% for DOX and SIM, respectively. A more pronounced inhibitory effect on breast cancer cell lines was observed at a DOX:SIM molar ratio of 2:1 in both free and encapsulated drugs. Furthermore, the 2:1 ratio showed synergistic combination rates for all concentrations of cell inhibition analyzed (50, 75, and 90%). The results demonstrated the promising potential of the co-encapsulated liposome for breast tumor treatment.

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Section: Discussionmentioning

confidence: 99%

Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines

et al. 2023

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“…[131] Similarly, Chen et al generated functional hybrids for photothermal therapy using thermosensitive liposomes (DPPC/DSPE-PEG/MSPC) loaded with a photosensitizing agent. [130] Additional studies based on EV drug loading via liposome fusion were conducted with the small molecules doxorubicin, [133] triptolide, [134] and clodronate. [135] Existing studies on LMs loaded the hybrids after fusion.…”

Section: Classification By Methodsmentioning

confidence: 99%

Standardization Approaches for Extracellular Vesicle Loading with Oligonucleotides and Biologics

Roerig

Schulz‐Siegmund

2023

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Extracellular vesicles (EVs) are widely recognized for their potential as drug delivery systems. EVs are membranous nanoparticles shed from cells. Among their natural features are their ability to shield cargo molecules against degradation and enable their functional internalization into target cells. Especially biological or bio‐inspired large molecules (LMs), like nucleic acids, proteins, peptides, and others, may profit from encapsulation in EVs for drug delivery purposes. In the last years, a variety of loading protocols are explored for different LMs. The lack of standardization in the EV drug delivery field has impeded their comparability so far. Currently, the first reporting frameworks and workflows for EV drug loading are proposed. The aim of this review is to summarize these evolving standardization approaches and set recently developed methods into context. This will allow for enhanced comparability of future work on EV drug loading with LMs.

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“…This property, which is different from that of normal tissues, provides new ideas for potential antitumor drug delivery. Gomes et al [ 208 ] fused breast cancer cell-derived exosomes with DOX-loaded long-circulating and pH-sensitive liposomes (SpHL-DOX) to obtain the hybrid exosome ExoSpHL-DOX. The results subsequently showed that ExoSpHL-DOX was sensitive to environmental pH and could selectively release antitumor drugs in an acidic environment.…”

Section: Exosomes In Tumor Therapymentioning

confidence: 99%

Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application

Yang,

Li,

et al. 2024

J Nanobiotechnol

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Malignancy is a major public health problem and among the leading lethal diseases worldwide. Although the current tumor treatment methods have therapeutic effect to a certain extent, they still have some shortcomings such as poor water solubility, short half-life, local and systemic toxicity. Therefore, how to deliver therapeutic agent so as to realize safe and effective anti-tumor therapy become a problem urgently to be solved in this field. As a medium of information exchange and material transport between cells, exosomes are considered to be a promising drug delivery carrier due to their nano-size, good biocompatibility, natural targeting, and easy modification. In this review, we summarize recent advances in the isolation, identification, drug loading, and modification of exosomes as drug carriers for tumor therapy alongside their application in tumor therapy. Basic knowledge of exosomes, such as their biogenesis, sources, and characterization methods, is also introduced herein. In addition, challenges related to the use of exosomes as drug delivery vehicles are discussed, along with future trends. This review provides a scientific basis for the application of exosome delivery systems in oncological therapy. Graphical Abstract

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Fusion of Tumor-Derived Exosomes with Long-Circulating and pH-Sensitive Liposomes Loaded with Doxorubicin for the Treatment of Breast Cancer

Cited by 13 publications

References 32 publications

Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines

Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines

Standardization Approaches for Extracellular Vesicle Loading with Oligonucleotides and Biologics

Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application

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