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Engineering blood exosomes for tumor-targeting efficient gene/chemo combination therapy.

ABSTRACT: Rationale: Developing an effective nanoplatform to realize 'multi-in-one' is essential to broaden the therapeutic potential of combination therapy. Exosomes are ideal candidates since their intrinsic abilities of integrating multiple contents and functions. However, only limited efforts have been devoted to engineering exosomes to integrate the needed properties, also considering the safety and yield, for tumor-targeted and efficient gene/chemo combination therapy. Methods: Herein, by manipulating the exosome membrane, blood exosomes with high abundance and safety are engineered as a versatile combinatorial delivery system, where the doxorubicin (Dox) and cholesterol-modified miRNA21 inhibitor (miR-21i) are co-embedded into the lipid bilayer of exosomes, and the magnetic molecules and endosomolytic peptides L17E are bind to the exosome membrane through ligand-receptor coupling and electrostatic interactions, respectively. Results: It is proved that such engineering strategy not only preserves their intrinsic features, but also readily integrates multiple properties of tumor targeting, efficient transfection and gene/chemo combination therapy into blood exosomes. The lipid bilayer structure of exosomes allows them to co-load Dox and miR-21i with high-payloads. Moreover, profiting from the integration of magnetic molecules and L17E peptides, the engineered exosomes exhibit an enhanced tumor accumulation and an improved endosome escape ability, thereby specifically and efficiently delivering encapsulated cargos to tumor cells. As a result, a remarkable inhibition of tumor growth is observed in the tumor-bearing mice, and without noticeable side effects. Conclusions: This study demonstrates the potential of engineered blood exosomes as feasible co-delivery nanosystem for tumor-targeted and efficient combination therapy. Further development by replacing the drugs combined regimens can potentially make this engineered exosome become a general platform for the design of safe and effective combination therapy modality.

SUBMITTER: Zhan Q

PROVIDER: S-EPMC7359100 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Engineering blood exosomes for tumor-targeting efficient gene/chemo combination therapy.

Zhan Qi Q Yi Kaikai K Qi Hongzhao H Li Sidi S Li Xueping X Wang Qixue Q Wang Yunfei Y Liu Chaoyong C Qiu Mingzhe M Yuan Xubo X Zhao Jin J Hou Xin X Kang Chunsheng C

Theranostics 20200622 17

<b>Rationale:</b> Developing an effective nanoplatform to realize 'multi-in-one' is essential to broaden the therapeutic potential of combination therapy. Exosomes are ideal candidates since their intrinsic abilities of integrating multiple contents and functions. However, only limited efforts have been devoted to engineering exosomes to integrate the needed properties, also considering the safety and yield, for tumor-targeted and efficient gene/chemo combination therapy. <b>Methods:</b> Herein, ...[more]

PMID: 32685027

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Project description:Simple Summary The tumor microenvironment encompasses the cellular and extracellular matrix components that support and shape the three-dimensional framework in which solid tumors develop and grow. The extracellular matrix of the tumor is characterized by increased deposition and aberrant architecture of collagen fibers. Therefore, as a key mechanical component of the tumor microenvironment, collagen plays a critical role in cancer progression, metastasis, and therapeutic response. To boost the efficacy of current anticancer therapies, including immunotherapy, innovative approaches should take into account strategies directed against the dysregulated non-cancer cell stromal components. In the current review, we provide an overview of the principal approaches to target tumor collagen to provide therapeutic benefits. Abstract The tumor stroma, which comprises stromal cells and non-cellular elements, is a critical component of the tumor microenvironment (TME). The dynamic interactions between the tumor cells and the stroma may promote tumor progression and metastasis and dictate resistance to established cancer therapies. Therefore, novel antitumor approaches should combine anticancer and anti-stroma strategies targeting dysregulated tumor extracellular matrix (ECM). ECM remodeling is a hallmark of solid tumors, leading to extensive biochemical and biomechanical changes, affecting cell signaling and tumor tissue three-dimensional architecture. Increased deposition of fibrillar collagen is the most distinctive alteration of the tumor ECM. Consequently, several anticancer therapeutic strategies have been developed to reduce excessive tumor collagen deposition. Herein, we provide an overview of the current advances and challenges of the main approaches aiming at tumor collagen normalization, which include targeted anticancer drug delivery, promotion of degradation, modulation of structure and biosynthesis of collagen, and targeting cancer-associated fibroblasts, which are the major extracellular matrix producers.

Dataset Information

Engineering blood exosomes for tumor-targeting efficient gene/chemo combination therapy.

Publications

Engineering blood exosomes for tumor-targeting efficient gene/chemo combination therapy.

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