Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy

Abstract

We report a novel cancer-targeted nanomedicine platform for imaging and prospect for future treatment of unresected ovarian cancer tumors by intraoperative multimodal phototherapy. To develop the required theranostic system, novel low-oxygen graphene nanosheets were chemically modified with polypropylenimine dendrimers loaded with phthalocyanine (Pc) as a photosensitizer. Such a molecular design prevents fluorescence quenching of the Pc by graphene nanosheets, providing the possibility of fluorescence imaging. Furthermore, the developed nanoplatform was conjugated with poly(ethylene glycol), to improve biocompatibility, and with luteinizing hormone-releasing hormone (LHRH) peptide, for tumor-targeted delivery. Notably, a low-power near-infrared (NIR) irradiation of single wavelength was used for both heat generation by the graphene nanosheets (photothermal therapy [PTT]) and for reactive oxygen species (ROS)-production by Pc (photodynamic therapy [PDT]). The combinatorial phototherapy resulted in an enhanced destruction of ovarian cancer cells, with a killing efficacy of 90%–95% at low Pc and low-oxygen graphene dosages, presumably conferring cytotoxicity to the synergistic effects of generated ROS and mild hyperthermia. An animal study confirmed that Pc loaded into the nanoplatform can be employed as a NIR fluorescence agent for imaging-guided drug delivery. Hence, the newly developed Pc-graphene nanoplatform has the significant potential as an effective NIR theranostic probe for imaging and combinatorial phototherapy.

Recent Advances in Laser Utilization in the Chemical Modification of Graphene Oxide and Its Applications

“…Taratula et al [ 122 ] reported a cancer-targeted nanomedicine platform for the imaging and treatment of un-resected ovarian cancer tumors by intraoperative multimodal phototherapy. To develop the required theranostic system, low-oxygen graphene nanosheets were chemically modifi ed with polypropylenimine (PPI) dendrimers loaded with phthalocyanine as a photosensitizer.…”

ROS-induced nanotherapeutic approach for ovarian cancer treatment based on the combinatorial effect of photodynamic therapy and DJ-1 gene suppression

“…Generation 4 poly(propylene imine) dendrimer (PPIG4) was purchased from SyMO-Chem (Netherlands 26,27,30 Synthesis of the DJ-1 siRNA delivery vehicle (PPI-siRNA) was carried out by first obtaining the PPIG4-siRNA complex via mixing DJ-1 siRNA (10 μM) and PPIG4 (0.33 μg/ml) in milliQ water. The mixture was incubated at room temperature (RT) for 1 h, followed by the addition of MAL-PEG-NHS (0.033 mg/mL).…”

“…26,31,32 Flow cytometery was used to evaluate cellular internalization efficiency of both the PPI-Pc and PPI-siRNA. 26,27 The amount of intracellular singlet oxygen ( 1 O 2 ) produced by PPI-Pc after light treatment was measured by the SOSG assay. 26 …”

“…26,27 The amount of intracellular singlet oxygen ( 1 O 2 ) produced by PPI-Pc after light treatment was measured by the SOSG assay. 26 …”

“…The structure of PPIG4 dendrimers, having a combination of interior hydrophobic pockets and peripheral hydrophilic primary amines, offer the possibility to encapsulate the hydrophobic Pc molecules, and thereby both decreasing their aggregation while enhancing water solubility 26,27,30 (Fig. 1A).…”