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Size-Tunable Gd₂O₃@Albumin Nanoparticles Conjugating Chlorin e6 for Magnetic Resonance Imaging-Guided Photo-Induced Therapy.

ABSTRACT: Protein nanoparticles as nanocarriers are of particular interest in the field of cancer therapy. Nevertheless, so far a facile fabrication of theranostic protein nanoparticles have been explored with limited success for cancer imaging and therapy. In this work, we demonstrate the controllable synthesis of size-tunable Gd₂O₃@albumin conjugating photosensitizer (PS) (GA-NPs) using hollow albumin as the nanoreactor for magnetic resonance imaging (MRI)-guided photo-induced therapy. The growth of Gd₂O₃ nanocrystals within the hollow nanoreactors is well regulated through reaction time, and a typical PS (e.g. chlorin e6) is further conjugated with the protein corona of the nanoreactor through facile chemical coupling, followed by the formation of theranostic GA-NPs. GA-NPs exhibit good longitudinal relaxivity, ideal photostability, enhanced cellular uptakes, and preferable size-dependent tumor accumulation. Moreover, GA-NPs effectively generate remarkable photothermal effect, intracellular reactive oxygen species from Ce6, and subsequent cytoplasmic drug translocation, thereby leading to severe synergistic photothermal and photodynamic cell damages. Consequently, GA-NPs exhibit an in vivo size-dependent MRI capacity with enhanced imaging contrast for effective tumor localization, and also generate a potent synergistic photodynamic therapy/photothermal therapy efficacy under irradiation owing to their enhanced tumor accumulation and strong photo-induced cytotoxicity. These results suggest that GA-NPs can act as a promising theranostic protein nanoplatform for cancer imaging and photo-induced therapy.

SUBMITTER: Zhou L

PROVIDER: S-EPMC5327648 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Size-Tunable Gd2O3@Albumin Nanoparticles Conjugating Chlorin e6 for Magnetic Resonance Imaging-Guided Photo-Induced Therapy.

Zhou Lijuan L Yang Tao T Wang Junxing J Wang Qiaoli Q Lv Xiaoyan X Ke Hengte H Guo Zhengqing Z Shen Junkang J Wang Yong Y Xing Chungen C Chen Huabing H

Theranostics 20170125 3

Protein nanoparticles as nanocarriers are of particular interest in the field of cancer therapy. Nevertheless, so far a facile fabrication of theranostic protein nanoparticles have been explored with limited success for cancer imaging and therapy. In this work, we demonstrate the controllable synthesis of size-tunable Gd2O3@albumin conjugating photosensitizer (PS) (GA-NPs) using hollow albumin as the nanoreactor for magnetic resonance imaging (MRI)-guided photo-induced ther ...[more]

PMID: 28255365

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Project description:The aim of this study is to prepare redox-sensitive nanophotosensitizers for the targeted delivery of chlorin e6 (Ce6) against cervical cancer. For this purpose, Ce6 was conjugated with β-cyclodextrin (bCD) via a disulfide bond, creating nanophotosensitizers that were fabricated for the redox-sensitive delivery of Ce6 against cancer cells. bCD was treated with succinic anhydride to synthesize succinylated bCD (bCDsu). After that, cystamine was attached to the carboxylic end of bCDsu (bCDsu-ss), and the amine end group of bCDsu-ss was conjugated with Ce6 (bCDsu-ss-Ce6). The chemical composition of bCDsu-ss-Ce6 was confirmed with 1H and 13C NMR spectra. bCDsu-ss-Ce6 nanophotosensitizers were fabricated by a dialysis procedure. They formed small particles with an average particle size of 152.0 ± 23.2 nm. The Ce6 release rate from the bCDsu-ss-Ce6 nanophotosensitizers was accelerated by the addition of glutathione (GSH), indicating that the bCDsu-ss-Ce6 nanophotosensitizers have a redox-sensitive photosensitizer delivery capacity. The bCDsu-ss-Ce6 nanophotosensitizers have a low intrinsic cytotoxicity against CCD986Sk human skin fibroblast cells as well as Ce6 alone. However, the bCDsu-ss-Ce6 nanophotosensitizers showed an improved Ce6 uptake ratio, higher reactive oxygen species (ROS) production, and phototoxicity compared to those of Ce6 alone. GSH addition resulted in a higher Ce6 uptake ratio, ROS generation, and phototoxicity than Ce6 alone, indicating that the bCDsu-ss-Ce6 nanophotosensitizers have a redox-sensitive biological activity in vitro against HeLa human cervical cancer cells. In a tumor xenograft model using HeLa cells, the bCDsu-ss-Ce6 nanophotosensitizers efficiently accumulated in the tumor rather than in normal organs. In other words, the fluorescence intensity in tumor tissues was significantly higher than that of other organs, while Ce6 alone did not specifically target tumor tissue. These results indicated a higher anticancer activity of bCDsu-ss-Ce6 nanophotosensitizers, as demonstrated by their efficient inhibition of the growth of tumors in an in vivo animal tumor xenograft study.

Dataset Information

Size-Tunable Gd₂O₃@Albumin Nanoparticles Conjugating Chlorin e6 for Magnetic Resonance Imaging-Guided Photo-Induced Therapy.

Publications

Size-Tunable Gd<sub>2</sub>O<sub>3</sub>@Albumin Nanoparticles Conjugating Chlorin e6 for Magnetic Resonance Imaging-Guided Photo-Induced Therapy.

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