Multifunctional Photosensitizer Grafted on Polyethylene Glycol and Polyethylenimine Dual-Functionalized Nanographene Oxide for Cancer-Targeted Near-Infrared Imaging and Synergistic Phototherapy.
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.
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, Department of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Shenglin
S
Luo
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, Department of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Zhangyou
Z
Yang
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, Department of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Xu
X
Tan
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, Department of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Yang
Y
Wang
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, Department of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Yiping
Y
Zeng
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, Department of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Yu
Y
Wang
Institute for Clean Energy and Advanced Materials, Southwest University , Chongqing 400715, China.
Changming
C
Li
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, Department of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Rong
R
Li
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, Department of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Chunmeng
C
Shi
D000818:Animals; D045744:Cell Line, Tumor; D006108:Graphite; D006801:Humans; D051379:Mice; D053758:Nanoparticles; D009369:Neoplasms; D010087:Oxides; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry*; D011092:Polyethylene Glycols; D011094:Polyethyleneimine
D010087:Oxides; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols; D006108:Graphite; D011094:Polyethyleneimine
cyanine dye; graphene oxide; photodynamic therapy; photothermal therapy; theranostics