Photothermal and photodynamic activity of polymeric nanoparticles based on α-tocopheryl succinate-RAFT block copolymers conjugated to IR-780

Abstract

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 808 nm. 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.

<p>Hybrid curcumin–phospholipid complex-near-infrared dye oral drug delivery system to inhibit lung metastasis of breast cancer</p>

“…Cellular uptake was also determined by flow cytometry. As shown in Figure 4C, NIR irradiation improved cellular uptake, in agreement with a previous report of photothermal effect promoting nanocarrier endocytosis and intracellular accumulation 45Figure 3Confocal images of cellular uptake for CUR/IR780@SMEDDS in Caco-2 cells and 4T1 cells.

Figure 4( A ) Confocal images of ROS generation by CUR/IR780@SMEDDS after NIR irradiation (808 nm, 0.8 W/cm 2 , 5 mins) in 4T1 cells.

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A Lipophilic IR-780 Dye-Encapsulated Zwitterionic Polymer-Lipid Micellar Nanoparticle for Enhanced Photothermal Therapy and NIR-Based Fluorescence Imaging in a Cervical Tumor Mouse Model

“…IR-780 dye is a hydrophobic heptamethine dye with higher fluorescent intensity than the Food and Drug Administration (FDA)-approved indocyanine green (ICG) dye, although it lacks solubility in aqueous solution and is eliminated more rapidly from the body system [ 3 ]. Hence, encapsulation of the IR-780 dye in amphiphilic micelle nanoparticles is expected to enhance its stability in aqueous solutions [ 4 , 5 , 6 ]. Ye Kuang et al encapsulated IR-780 dye in cyclic RGD-conjugated solid lipid nanoparticles and elucidated the enhanced NIR live-image-guided photothermal ablation of U87MG tumors [ 7 ].…”

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

“…Moreover, it can also enhance the inhibition of tumor growth as in case of ionizing radiation and hyperthermia therapy (Prasad et al., 2003 ; Angulo-Molina et al., 2014 ). Because of the anticancer activities of αTS and its derivatives, they have been used as a component of nanoparticles for cancer therapy (Zeng et al., 2013 ; Tao et al., 2015 ; Zeng et al., 2015 ; Mallick et al., 2016 ; Muddineti et al., 2017 ; Palao-Suay et al., 2017 ). Herein, αTS-conjugated Lys (Lys-αTS) was synthesized and curcumin (CUR) was incorporated into the Lys-αTS nanoassembly (NA).…”