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An ?-tocopheryl succinate enzyme-based nanoassembly for cancer imaging and therapy.

ABSTRACT: Nanoassembly (NA) based on a D-?-tocopherol succinate (?TS) conjugated lysozyme (Lys) (Lys-?TS) was fabricated for tumor-selective delivery of curcumin (CUR) for breast cancer therapy. Lys and ?TS were used as a biocompatible enzyme and a hydrophobic residue, respectively, for the preparation of nanocarriers in this study. Compared with CUR-loaded cross-linked Lys (c-Lys/CUR) NA, Lys-?TS/CUR NA exhibited a smaller hydrodynamic size (213?nm mean diameter), a narrower size distribution, and a more spherical shape. Sustained drug release was observed from the Lys-?TS/CUR NA for five days at a normal physiological pH (pH 7.4). The developed Lys-?TS/CUR NA showed enhanced cellular accumulation, antiproliferative effects, and apoptotic efficacies in MDA-MB-231 human breast adenocarcinoma cells. According to the results of optical imaging test in the MDA-MB-231 tumor-bearing mouse models, the Lys-?TS/CUR NA-injected group exhibited a more tumor-selective accumulation pattern, rather than being distributed in the normal tissues and organs. The observed tumor targetability of Lys-?TS/CUR was further studied, which revealed improved in vivo anticancer activities (better inhibition of tumor growth and induction of apoptosis in the tumor tissue) after an intravenous administration in the MDA-MB-231 tumor-bearing mouse models. All these results indicate that the newly developed enzyme-based nanocarrier, the Lys-?TS NA, can be a promising candidate for the therapy of breast cancers.

SUBMITTER: Lee SY

PROVIDER: S-EPMC6058571 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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An α-tocopheryl succinate enzyme-based nanoassembly for cancer imaging and therapy.

Lee Song Yi SY Cho Hyun-Jong HJ

Drug delivery 20181101 1

Nanoassembly (NA) based on a D-α-tocopherol succinate (αTS) conjugated lysozyme (Lys) (Lys-αTS) was fabricated for tumor-selective delivery of curcumin (CUR) for breast cancer therapy. Lys and αTS were used as a biocompatible enzyme and a hydrophobic residue, respectively, for the preparation of nanocarriers in this study. Compared with CUR-loaded cross-linked Lys (c-Lys/CUR) NA, Lys-αTS/CUR NA exhibited a smaller hydrodynamic size (213 nm mean diameter), a narrower size distribution, and a more ...[more]

PMID: 29516756

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Project description:The aim of this work was the generation of a multifunctional nanopolymeric system that incorporates IR-780 dye, a near-infrared (NIR) imaging probe that exhibits photothermal and photodynamic properties; and a derivate of α-tocopheryl succinate (α-TOS), a mitochondria-targeted anticancer compound. IR-780 was conjugated to the hydrophilic segment of copolymer PEG-b-polyMTOS, based on poly(ethylene glycol) (PEG) and a methacrylic derivative of α-tocopheryl succinate (MTOS), to generate IR-NP, self-assembled nanoparticles (NPs) in aqueous media which exhibit a hydrophilic shell and a hydrophobic core. During assembly, the hydrophobic core of IR-NP could encapsulate additional IR-780 to generate derived subspecies carrying different amount of probe (IR-NP-eIR). Evaluation of photo-inducible properties of IR-NP and IR-NP-eIR were thoroughly assessed in vitro. Developed nanotheranostic particles showed distinct fluorescence and photothermal behavior after excitation by a laser light emitting at 808nm. Treatment of MDA-MB-453 cells with IR-NP or IR-NP-eIR resulted in an efficient internalization of the IR-780 dye, while subsequent NIR-laser irradiation led to a severe decrease in cell viability. Photocytoxicity conducted by IR-NP, which could not be attributed to the generation of lethal hyperthermia, responded to an increase in the levels of intracellular reactive oxygen species (ROS). Therefore, the fluorescence imaging and inducible phototoxicity capabilities of NPs derived from IR-780-PEG-b-polyMTOS copolymer confer high value to these nanotheranostics tools in clinical cancer research.Statement of significanceMultifunctional polymeric nanoparticles (NPs) that combine imaging and therapeutic properties are highly valuable in cancer treatment. In this paper we describe the development of NPs that are fluorescent in the near-infrared (NIR). This is important for their visualization in living tissues that present low absorption and low autofluorescence in this wavelength region (between 700 and 1000nm). Moreover, NPs present photothermal and photodynamic properties when NIR irradiated: the NPs produce an efficient increment of temperature and increase the intracellular reactive oxygen species (ROS) when laser irradiated at 808nm. These tuneable photoinduced properties make the NPs highly cytotoxic after NIR irradiation and provide a new tool for highly precise cancer treatment.

Dataset Information

An ?-tocopheryl succinate enzyme-based nanoassembly for cancer imaging and therapy.

Publications

An α-tocopheryl succinate enzyme-based nanoassembly for cancer imaging and therapy.

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