Enhanced fluorescence imaging guided photodynamic therapy of sinoporphyrin sodium loaded graphene oxide
Introduction
Photodynamic theranostics, due to the specific spatiotemporal selectivity and minimal invasiveness, is an emerging solution that promises simultaneous photosensitizer (PS) fluorescence imaging and photodynamic therapy (PDT) [1], [2], [3], [4], [5], [6]. Based on the activation of light with appropriate wavelengths, PS can emit fluorescence via the relaxation of the excited-singlet-state PS back to the ground state, which can be employed for the photodiagnosis of disease, real-time visualization of in vivo PS delivery and distribution, and molecular imaging-guided PDT [1], [2]. Additionally, PS can transfer the absorbed photon energy to surrounding oxygen molecules, resulting in the production of reactive oxygen species (ROS) including singlet oxygen or free radicals, which cause cancer cell death and tumor tissue destruction [7], [8], [9].
Most PSs used in PDT are limited by prolonged cutaneous photosensitivity, poor water-solubility and inadequate selectivity [10], [11], [12]. To improve the water solubility of PS molecules and increase their accumulation into cancer cells/tissues, various nanocarriers such as liposomes and polymer-, silica-, magnetic-, gold-, and carbon-based nanoparticles (NPs) have been actively developed for the delivery of PS [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]. Although these nanocarriers can improve tumor accumulation efficiency of PS via the enhanced permeability and retention (EPR) effect over free PS, the fluorescence of PS is often quenched in varying degrees by the nanocarriers [10], [16], [17], [23], [24], [25]. Therefore, the development of novel PS delivery system without fluorescence quenching is desirable for optimizing PS fluorescence imaging and PDT.
Among the various nanocarriers, graphene oxide (GO), due to the large surface area, water solubility, abundant functional groups (epoxide, hydroxyl, and carboxylic groups) and easy surface modification, has been widely employed for biosensing, bioimaging, and drug/gene delivery [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37]. GO shows great potential as an efficient quencher in GO-based nanosensors for many fluorescent moieties, including small molecule dyes, quantum dots and conjugated polymers via fluorescence resonance energy transfer or charge transfer [38], [39], [40], [41], [42]. Most recently, researchers have combined GO with PS for fluorescence imaging and PDT [16], [23], [24]. However, the drastic fluorescence quenching of PSs by GO in GO-based PS delivery system limits their potential as photodiagnostics. In our previous studies, we found that the fluorescence of chlorin e6 (Ce6) was drastically quenched by folic acid-conjugated GO [16]. Recently, we also observed 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH) fluorescence quenching by GO-PEG [24]. The similar results were also verified in the studies from other groups [23]. Therefore, there still remains a grand challenge to improve GO-based PS delivery system without fluorescence quenching.
In this study, we designed and validated a novel phototheranostic nanoplatform based on sinoporphyrin sodium (DVDMS) photosensitizer-loaded PEGylated GO (GO-PEG-DVDMS) for enhanced fluorescence imaging guided PDT. DVDMS (Scheme 1), a porphyrin dimer salt, has been used as a new type of PS with high yield of fluorescent emission at the wavelengths of 615–625 nm for diagnosis and treatment of cancer [43], [44].
Section snippets
Materials
DVDMS photosensitizer was provided by Jiangxi Qinglong Group Co., Ltd. (Jiangxi, China). Amine-terminated eight-arm branched PEG (Mw: 15,000) was purchased from NOF America Corporation (White Plains, NY). N-(3-dimethylaminopropyl-N-ethylcarbodiimide) hydrochloride (EDC) was obtained from Fluka Inc. Singlet oxygen sensor green (SOSG), DAPI (SlowFade® Gold Antifade Reagent with DAPI, Molecular Probes), and live/dead stain kit were purchased from Invitrogen. All the above chemicals were used
Synthesis and characterization of GO-PEG-DVDMS
GO was prepared using flake expandable graphite as the raw material by a modified Hummers method. Amine terminated eight-arm branched PEG was conjugated with GO sheets to improve their aqueous dispersibility, stability, and biocompatibility [48]. Subsequently, DVDMS was loaded onto the two accessible surfaces of GO via hydrophobic interactions and π-π stacking. Atomic force microscope (AFM) imaging showed that the size of GO-PEG was less than 50 nm and the thickness was ∼1.5 nm (Fig. 1A and C).
Conclusion
In summary, we successfully developed a novel photo-theranostic platform based on sinoporphyrin sodium (DVDMS) photosensitizer-loaded PEGylated GO (GO-PEG-DVDMS) for enhanced fluorescence imaging guided PDT. The fluorescence property of DVDMS was significantly enhanced after GO-PEG loading via intramolecular charge transfer, which facilitates enhanced fluorescence imaging. Meanwhile, GO-PEG can improve the tumor accumulation efficiency of DVDMS compared to free DVDMS. We validated the strong
Acknowledgments
This work was supported, in part, by the National Basic Research Program of China (2013CB733802, 2014CB744503, 2015CB931800 and 2015CB931803), National Natural Science Foundation of China (81371596, 81401465, 81130028, 31210103913), the Key Grant Project of Heilongjiang Province (GA12C302), the Ph.D. Programs Foundation of Ministry of Education of China (201123071100203), the Key Laboratory of Molecular Imaging Foundation(College of Heilongjiang Province) and by the intramural research program
References (48)
- et al.
Development and applications of photo-triggered theranostic agents
Adv Drug Deliv Rev
(2010) - et al.
Photosensitizer-conjugated silica-coated gold nanoclusters for fluorescence imaging-guided photodynamic therapy
Biomaterials
(2013) - et al.
Nanoparticles as vehicles for delivery of photodynamic therapy agents
Trends Biotechnol
(2008) - et al.
Photosensitizer-conjugated magnetic nanoparticles for in vivo simultaneous magnetofluorescent imaging and targeting therapy
Biomaterials
(2011) - et al.
Preparation of purpurin-18 loaded magnetic nanocarriers in cottonseed oil for photodynamic therapy
Mater Lett
(2008) - et al.
Tumor vasculature targeting and imaging in living mice with reduced graphene oxide
Biomaterials
(2013) - et al.
High-efficiency loading of hypocrellin B on graphene oxide for photodynamic therapy
Carbon
(2012) - et al.
The influence of surface chemistry and size of nanoscale graphene oxide on photothermal therapy of cancer using ultra-low laser power
Biomaterials
(2012) - et al.
Activatable photosensitizers for imaging and therapy
Chem Rev
(2010) - et al.
Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents
Nat Mater
(2011)
Light-triggered theranostics based on photosensitizer-conjugated carbon dots for simultaneous enhanced-fluorescence imaging and photodynamic therapy
Adv Mater
Imaging and photodynamic therapy: mechanisms, monitoring, and optimization
Chem Rev
Unique diagnostic and therapeutic roles of porphyrins and phthalocyanines in photodynamic therapy, imaging and theranostics
Theranostics
Photodynamic therapy
J Natl Cancer Inst
New technology for deep light distribution in tissue for phototherapy
Cancer J
Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy
Nanotechnology
Studies on preparation of photosensitizer loaded magnetic silica nanoparticles and their anti-tumor effects for targeting photodynamic therapy
Nanoscale Res Lett
Nanomaterials and singlet oxygen photosensitizers: potential applications in photodynamic therapy
J Mater Chem
Photosensitizer-loaded gold vesicles with strong plasmonic coupling effect for imaging-guided photothermal/photodynamic therapy
ACS Nano
Folic acid-conjugated graphene oxide loaded with photosensitizers for targeting photodynamic therapy
Theranostics
Single continuous wave laser induced photodynamic/plasmonic photothermal therapy using photosensitizer-functionalized gold nanostars
Adv Mater
Regulation of singlet oxygen generation using single-walled carbon nanotubes
J Am Chem Soc
Assembly of aptamer switch probes and photosensitizer on gold nanorods for targeted photothermal and photodynamic cancer therapy
ACS Nano
Photosensitizer–gold nanorod composite for targeted multimodal therapy
Small
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