Multifunctional Photosensitizer Grafted on Polyethylene Glycol and Polyethylenimine Dual-Functionalized Nanographene Oxide for Cancer-Targeted Near-Infrared Imaging and Synergistic Phototherapy

Abstract

The integration of photodynamic therapy (PDT) with photothermal therapy (PTT) offers improved efficacy in cancer phototherapy. Herein, a PDT photosensitizer (IR-808) with cancer-targeting ability and near-infrared (NIR) sensitivity was chemically conjugated to both polyethylene glycol (PEG)- and branched polyethylenimine (BPEI)-functionalized nanographene oxide (NGO). Because the optimal laser wavelength (808 nm) of NGO for PTT is consistent with that of IR-808 for PDT, the IR-808-conjugated NGO sheets (NGO-808, 20-50 nm) generated both large amounts of reactive oxygen species (ROS) and local hyperthermia as a result of 808 nm laser irradiation. With PEG- and BPEI-modified NGO as the carrier, the tumor cellular uptake of NGO-808 exhibited higher efficacy than that of strongly hydrophobic free IR-808. Through evaluation with both human and mouse cancer cells, NGO-808 was demonstrated to provide significantly enhanced PDT and PTT effects compared to individual PDT using IR-808 or PTT using NGO. Furthermore, NGO-808 preferentially accumulated in cancer cells as mediated by organic-anion transporting polypeptides (OATPs) overexpressed in many cancer cells, providing the potential for highly specific cancer phototherapy. Using the targeting ability of NGO-808, in vivo NIR fluorescence imaging enabled tumors and their margins to be clearly visualized at 48 h after intravenous injection, providing a theranostic platform for imaging-guided cancer phototherapy. Remarkably, after a single injection of NGO-808 and 808 nm laser irradiation for 5 min, the tumors in two tumor xenograft models were ablated completely, and no tumor recurrence was observed. After treatment with NGO-808, no obvious toxicity was detected in comparison to control groups. Thus, high-performance cancer phototherapy with minimal side effects was afforded from synergistic PDT/PTT treatment and cancer-targeted accumulation of NGO-808.

Recent Advances in Carbon Nanomaterials for Cancer Phototherapy

“…b) Preparation of NGO‐808 and its high‐performance PTT/PDT of cancer by the enhanced tumor accumulation of NGO via IR‐808‐mediated OATP transport. Reproduced from reference . Copyright 2016 American Chemical Society.…”

Prototypic Heptamethine Cyanine Incorporating Nanomaterials for Cancer Phototheragnostic

“…Besides these heptamethine cyanines, IR775, IR797, IR806, IR820, IR825, Cypate, IRDye 800CW, and FD‐1080 also have promising optical properties (please see Table for further details). In the particular case of IR780, IR783, and IR808, these have been reported to interact with the organic anionic transporter peptides (OATPs), which are overexpressed by cancer cells, enabling their use for tumor imaging (please note that imaging applications require the administration of low doses of the imaging agents (e.g., 0.2–0.3 mg kg −1 )).…”

“…Nanomaterials incorporating IR808 (also known as MHI‐148) have also been showing promising properties for cancer PTT/PDT as well as for the visualization of tumors through NIR fluorescence imaging and PAI ( Tables 5 and ). For this purpose, IR808 (a carboxylated heptamethine cyanine) has been covalently conjugated to polymeric backbones, which are subsequently used in the preparation of IR808 based nanoparticles …”

“…In another work, IR808 was conjugated to the primary amine groups of poly(ethylenimine) (PEI)‐PEG‐graphene oxide (GO), leading to the assembly of nanostructures with photodynamic potential (conferred by IR808) and enhanced photothermal capacity (conferred by IR808 and GO) . The NIR imaging of the tumor bearing mice revealed the ability of these nanomaterials to accumulate at the tumor site.…”

“…PBS (−): PBS; PBS (+): PBS + NIR radiation; NGO‐PEG‐BPEI (+): PEI‐PEG‐GO + NIR radiation; IR808 (+): IR808 + NIR radiation; NGO‐808 (−): IR808‐PEI‐PEG‐GO; NGO‐808 (+): IR808‐PEI‐PEG‐GO + NIR radiation; NIR radiation: 808 nm; 1.0 W cm −2 ; 5 min. Reproduced with permission . Copyright 2016, American Chemical Society.…”