Gold Nanoparticle-Enhanced and Size-Dependent Generation of Reactive Oxygen Species from Protoporphyrin IX

Abstract

Photosensitizer, protoporphyrin IX (PpIX), was conjugated with Au nanoparticles (Au NPs) of 19, 66, and 106 nm diameter to study the size-dependent enhancement of reactive oxygen species (ROS) formation enabled by Au NPs. The ROS enhancement ratio is determined to be 1:2.56:4.72 in order of increasing Au NP size, in general agreement with theoretically calculated field enhancement to the fourth power. The convergence of the experimental and simulated results suggests that Au NP-enhanced and size-dependent ROS formation can be attributed directly to the localized electromagnetic field as a result of surface plasmonic resonance of Au NPs under light irradiation. In vitro study on the ROS formation enabled by PpIX-conjugated Au NPs in human breast cancer cells (MDA-MB-231) revealed the similar size-dependent enhancement of intracellular ROS formation, while the enhancement greatly depended on cellular uptake of Au NPs. Cellular photodynamic therapy revealed that cell destruction significantly increased in the presence of Au NPs. Compared to the untreated control (0% destruction), 22.6% cell destruction was seen in the PpIX alone group and more than 50% cell destruction was obtained for all PpIX-conjugated Au NPs. The 66 nm Au NPs yielded the highest cell destruction, consistent with the highest cellular uptake and highest ROS formation. Clearly, the complex cellular environment, size-dependent cellular uptake of Au NPs, and ROS generations are vital contributors to the overall cellular PDT efficacy.

Photodynamic nanomedicine in the treatment of solid tumors: Perspectives and challenges

“…It was found that the nanoparticles were taken up through lysosomal mechanisms and caused ∼50% cell death due to apoptosis [31]. Porphyrin derivatives such as Photofrin and protoporphyrin IX have been formulated in several different nanoparticle systems such as metal oxide, chitosan, polymeric, silica and gold nanoparticles (examples shown in Figures 3A and 3B) [32–53]. While majority of these formulations have envisioned the EPR mechanism to be utilized to passively target solid tumors, some have utilized receptor-mediated active targeting to enhance cell-selective delivery.…”

Synergistic Integration of Layer-by-Layer Assembly of Photosensitizer and Gold Nanorings for Enhanced Photodynamic Therapy in the Near Infrared

“…54 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 30 The viability of cells was determined by the thiazolyl blue tetrazolium bromide (MTT, Sigma) assay. Briefly, the cells after different treatments were incubated with 0.5 mg/mL MTT in cell culture medium for 2 h at 37 °C.…”

Water soluble, multifunctional antibody-porphyrin gold nanoparticles for targeted photodynamic therapy

“…13 Another porphyrin derivative, protoporphyrin IX was reacted with a positively charged branched polyethyleneimine on the surface of gold nanoparticles yielding water stable nanostructures useful for PDT. 14 Zaruba et al attached two porphyrin-brucine conjugates to 3-mercaptopropanoic acid modified gold nanoparticles (ca. 14.7 nm) yielding two types of porphyrin-stabilised nanoparticles that could be dispersed in culture media and that were tested for PDT both in vitro and in vivo.…”