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Near-Infrared Fluorescent pH Responsive Probe for Targeted Photodynamic Cancer Therapy.

ABSTRACT: We developed a pH dependent amino heptamethine cyanine based theranostic probe (I2-IR783-Mpip) that can be activated by near infrared light. I2-IR783-Mpip, in acidic condition, exhibited an intense, broad NIR absorption band (820-950?nm) with high singlet oxygen generation upon exposure to NIR light (~850?nm). Theoretical calculations showed that the protonation of the probe in an acidic environment decreased the molecular orbital energy gaps and increased the intramolecular charge transfer efficiency. I2-IR783-Mpip exhibited good photodynamic efficiency towards liver hepatocellular carcinoma cells under physiological and slightly acidic conditions while normal human embryonic kidney cells remained alive under the same conditions. Detection of intracellular reactive oxygen species (ROS) in cells treated with I2-IR783-Mpip after NIR light exposure confirmed PDT efficiency of the probe in acidic environment. Moreover, I2-IR783-Mpip also demonstrated efficient phototoxicity under deep-seated tumour cell system. We believed this is the first PDT agent that possesses intrinsic tumour binding and selectively eradicate tumour in acidic environment under 850?nm NIR lamp.

SUBMITTER: Siriwibool S

PROVIDER: S-EPMC6987190 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Near-Infrared Fluorescent pH Responsive Probe for Targeted Photodynamic Cancer Therapy.

Siriwibool Siriwalee S Kaekratoke Nantawat N Chansaenpak Kantapat K Siwawannapong Kittipan K Panajapo Pannipa P Sagarik Kritsana K Noisa Parinya P Lai Rung-Yi RY Kamkaew Anyanee A

Scientific reports 20200128 1

We developed a pH dependent amino heptamethine cyanine based theranostic probe (I<sub>2</sub>-IR783-Mpip) that can be activated by near infrared light. I<sub>2</sub>-IR783-Mpip, in acidic condition, exhibited an intense, broad NIR absorption band (820-950 nm) with high singlet oxygen generation upon exposure to NIR light (~850 nm). Theoretical calculations showed that the protonation of the probe in an acidic environment decreased the molecular orbital energy gaps and increased the intramolecula ...[more]

PMID: 31992821

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Project description:BACKGROUND:To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance. METHODS:The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96?h postinjection, and the biodistribution assays were performed using NIRF imaging. RESULTS:In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs. CONCLUSIONS:COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.

Project description:Photodynamic therapy (PDT) and photothermal therapy (PTT) have garnered considerable interest as non-invasive cancer treatment modalities. However, these approaches remain limited by low solubility, poor stability and inefficient targeting of many common photosensitizers (PSs) and photothermal agents (PTAs). To overcome these limitations, we have designed biocompatible and biodegradable tumor-targeted upconversion nanospheres with imaging capabilities. The multifunctional nanospheres consist of a sodium yttrium fluoride core doped with lanthanides (ytterbium, erbium and gadolinium) and bismuth selenide (NaYF 4 :Yb/Er/Gd,Bi 2 Se 3 ) within a mesoporous silica shell that encapsulates a PS, Chlorin e6 (Ce6), in its pores. NaYF 4 :Yb/Er converts deeply penetrating near-infrared (NIR) light to visible light, which excites the Ce6 to generate cytotoxic reactive oxygen species (ROS), while the PTA Bi 2 Se 3 efficiently converts absorbed NIR light to heat. Additionally, Gd enables magnetic resonance imaging (MRI) of the nanospheres. The mesoporous silica shell is coated with lipid/polyethylene glycol (DPPC/cholesterol/DSPE-PEG) to ensure retention of the encapsulated Ce6 and minimize interactions with serum proteins and macrophages that impede tumor targeting. Finally, the coat is functionalized with the acidity-triggered rational membrane (ATRAM) peptide, which promotes specific and efficient internalization into cancer cells within the mildly acidic tumor microenvironment. Following uptake by cancer cells in vitro , NIR laser irradiation of the nanospheres caused substantial cytotoxicity due to ROS production and hyperthermia. The nanospheres facilitated tumor MRI and thermal imaging, and exhibited potent NIR laser light-induced antitumor effects in vivo via combined PDT and PTT, with no observable toxicity to healthy tissue, thereby substantially prolonging survival. Our results demonstrate that the ATRAM-functionalized, lipid/PEG-coated upconversion mesoporous silica nanospheres (ALUMSNs) offer multimodal diagnostic imaging and targeted combinatorial cancer therapy.

Dataset Information

Near-Infrared Fluorescent pH Responsive Probe for Targeted Photodynamic Cancer Therapy.

Publications

Near-Infrared Fluorescent pH Responsive Probe for Targeted Photodynamic Cancer Therapy.

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