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Tumor-Homing pH-Sensitive Extracellular Vesicles for Targeting Heterogeneous Tumors.

ABSTRACT: In this study, we fabricated tumor-homing pH-sensitive extracellular vesicles for efficient tumor treatment. These vesicles were prepared using extracellular vesicles (EVs; BTEVs extracted from BT-474 tumor cells or SKEVs extracted from SK-N-MC tumor cells), hyaluronic acid grafted with 3-(diethylamino)propylamine (HDEA), and doxorubicin (DOX, as a model antitumor drug). Consequently, HDEA/DOX anchored EVs (HDEA@EVs) can interact with origin tumor cells owing to EVs' homing ability to origin cells. Therefore, EV blends of HDEA@BTEVs and HDEA@SKEVs demonstrate highly increased cellular uptake in both BT-474 and SK-N-MC cells: HDEA@BTEVs for BT-474 tumor cells and HDEA@SKEVs for SK-N-MC tumor cells. Furthermore, the hydrophobic HDEA present in HDEA@EVs at pH 7.4 can switch to hydrophilic HDEA at pH 6.5 as a result of acidic pH-induced protonation of 3-(diethylamino)propylamine (DEAP) moieties, resulting in an acidic pH-activated EVs' disruption, accelerated release of encapsulated DOX molecules, and highly increased cell cytotoxicity. However, EV blends containing pH-insensitive HA grafted with deoxycholic acid (HDOC) (HDOC@BTEVs and HDOC@SKEVs) showed less cell cytotoxicity for both BT-474 and SK-N-MC tumor cells, because they did not act on EVs' disruption and the resulting DOX release. Consequently, the use of these tumor-homing pH-sensitive EV blends may result in effective targeted therapies for various tumor cells.

SUBMITTER: Park J

PROVIDER: S-EPMC7238000 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Tumor-Homing pH-Sensitive Extracellular Vesicles for Targeting Heterogeneous Tumors.

Park Jaeduk J Lee Hyuk H Youn Yu Seok YS Oh Kyung Taek KT Lee Eun Seong ES

Pharmaceutics 20200417 4

In this study, we fabricated tumor-homing pH-sensitive extracellular vesicles for efficient tumor treatment. These vesicles were prepared using extracellular vesicles (EVs; BTEVs extracted from BT-474 tumor cells or SKEVs extracted from SK-N-MC tumor cells), hyaluronic acid grafted with 3-(diethylamino)propylamine (HDEA), and doxorubicin (DOX, as a model antitumor drug). Consequently, HDEA/DOX anchored EVs (HDEA@EVs) can interact with origin tumor cells owing to EVs' homing ability to origin cel ...[more]

PMID: 32316679

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Project description:PurposeZinc phthalocyanine (ZnPc) has been applied widely in photodynamic therapy (PDT) with high ROS-production capacity and intense absorption in the near-infrared region. However, weak tumor targeting and the aggregation tendency of ZnPc seriously affect the therapeutic effect of PDT. Therefore, overcoming the aggregation of ZnPc and enhancing its antitumor effect were the purpose of this study.MethodsIn this study, we first found that the aggregation behaviors of the photosensitizer ZnPc(TAP)4, ZnPc substituted by tertiary amine groups, were regulated finely by pH and that ZnPc(TAP)4 could be disaggregated gradually as the pH descended. ZnPc(TAP)4 and human serum albumin (HSA) molecules were assembled into nanoparticles (NPs) for tumor targeting. Meanwhile, the chemotherapy drug paclitaxel (Ptx) was loaded into HSA NPs together with ZnPc(TAP)4 for dual antitumor effects. HSA NPs loading both ZnPc(TAP)4 and Ptx (NP-ZnPc[TAP]4-Ptx) were characterized by particle size and in vitro release. Cytotoxicity, subcellular localization, tumor targeting, and anticancer effect in vivo were investigated respectively.ResultsWe found that NP-ZnPc(TAP)4-Ptx had good stability with qualifying particle size. Interestingly, ZnPc(TAP)4 was released from the NPs and the photodynamic activity enhanced in the acidic environment of tumor. In addition, NP-ZnPc(TAP)4-Ptx had prominent cytotoxicity and time-dependent subcellular localization characteristics. Through a three-dimensional animal imaging system, NP-ZnPc(TAP)4-Ptx showed much-enhanced tumor targeting in tumor-bearing mice. Above all, NP-ZnPc(TAP)4-Ptx was demonstrated to have the synergistic anticancer effect of PDT and chemotherapy.ConclusionNP-ZnPc(TAP)4-Ptx had enhanced tumor targeting for the pH-sensitive property of ZnPc(TAP)4 and the transport function of HSA. NP-ZnPc(TAP)4-Ptx possessed a double-anticancer effect through the combination of ZnPc(TAP)4 and Ptx. This drug-delivery system may also be used to carry chemotherapy drugs other than Ptx for improving antitumor effects.

Dataset Information

Tumor-Homing pH-Sensitive Extracellular Vesicles for Targeting Heterogeneous Tumors.

Publications

Tumor-Homing pH-Sensitive Extracellular Vesicles for Targeting Heterogeneous Tumors.

Similar Datasets

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