No 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.

Positively charged Au NPs were preferably taken up by breast cancer cells. Combination of positive surface charge with mitochondria-targeting domain onto Au NPs allowed their accumulation in the mitochondria of breast cancer cells to significantly elevate reactive oxygen species formation in 5-aminolevulinic-acid-enabled photodynamic therapy and improve selective destruction of breast cancer cells.

Photodynamic therapy (PDT) is a minimally invasive therapeutic strategy for cancer treatment, which can destroy local tumor cells and induce systemic antitumor immune response, whereas, focusing on improving direct cytotoxicity to tumor cells treated by PDT, there is growing interest in developing approaches to further explore the immune stimulatory properties of PDT. In this review we summarize the current knowledge of the innate and adaptive immune responses induced by PDT against tumors, providing evidence showing PDT facilitated-antitumor immunity. Various immunotherapeutic approaches on different cells are reviewed for their effectiveness in improving the treatment efficiency in concert with PDT. Future perspectives are discussed for further enhancing PDT efficiency via intracellular targetable drug delivery as well as optimized experimental model development associated with the study of antitumor immune response.

In recognition of the limitations of monolayer cell cultures and resource-intensive animal studies, a microfluidic culture system was developed for creation of physiologically relevant three-dimensional (3D) tissues. In this study, an in vitro 3D breast cancer tissue model was established in a microfluidic system with human breast cancer cells (MCF-7) and primary adipose-derived stromal cells (ASCs). It was evaluated for utility in determining the efficiency of photodynamic therapy (PDT) with therapeutic agents (i.e. photosensitizer and gold nanoparticles) under various irradiation conditions. We demonstrated, for the first time, the potential use of a microfluidic-based in vitro 3D breast cancer model for effective evaluation of PDT, with the capability of controlling 3D microenvironments for breast cancer tissue formation, real-time monitoring of tissue progression, implementing a circulation-like dynamic medium flow and drug supplements, and investigating the relation between light penetration and tissue depth in PDT.