Ablation of Hypoxic Tumors with Dose-Equivalent Photothermal, but Not Photodynamic, Therapy Using a Nanostructured Porphyrin Assembly

Abstract

Tumor hypoxia is increasingly being recognized as a characteristic feature of solid tumors and significantly complicates many treatments based on radio-, chemo-, and phototherapies. While photodynamic therapy (PDT) is based on photosensitizer interactions with diffused oxygen, photothermal therapy (PTT) has emerged as a new phototherapy that is predicted to be independent of oxygen levels within tumors. It has been challenging to meaningfully compare these two modalities due to differences in contrast agents and irradiation parameters, and no comparative in vivo studies have been performed until now. Here, by making use of recently developed nanostructured self-quenched porphysome nanoparticles, we were able to directly compare PDT and PTT using matched light doses and matched porphyrin photosensitizer doses (with the photosensitizer being effective for either PTT or PDT based on the existence of nanostructure or not). Therefore, we demonstrated the nanostructure-driven conversion from the PDT singlet oxygen generating mechanism of porphyrin to a completely thermal mechanism, ideal for PTT enhancement. Using a novel hypoxia tumor model, we determined that nanostructured porphyrin PTT enhancers are advantageous to overcome hypoxic conditions to achieve effective ablation of solid tumors.

Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage

“…Intrinsic copper-64 labeling allows for preoperative PET imaging of PLP delivery as well as sensitive and accurate detection of various primary and metastatic tumor types in mouse models. Its smaller size and prompt intracellular uptake compared with previously reported porphysome nanoparticles (21,22) result in more efficient nanostructure accumulation and dissociation in tumors. This fast accumulation and dissociation releases fluorescence and photodynamic reactivity, which are highly-silenced in intact PLP, providing an attractive activation mechanism for low-background NIR fluorescence imaging and tumor-selective PDT (20).…”

Recent advances in the development of organic photothermal nano-agents

“…Porphysomes can absorb and convert light energy into heat with high efficiency due to the high porphyrin packing density, making them promising candidates in PTT [55,56].…”

“…High efficiency in tumor ablation was achieved under laser irradiation in their in vivo experiments (Fig. 2) [55][56][57]. By changing the ways that porphyrin-lipid assembles were formed, ultra small porphyrin nanodiscs and large porphyrin shell microbubbles were fabricated in their later studies, for applications in photodynamic therapy and ultrasound imaging, respectively [58,59].…”

Rethinking translational nanomedicine: insights from the ‘bottom-up’ design of the Porphysome for guiding the clinical development of imageable nanomaterials

“…In vivo investigations of the antitumoural efficacy of Porphysome photodynamic [28,29] and photothermal [10 ,20 ,28,29,30] therapies, as well as on the photoacoustic [10 ,30,31] and fluorescence [10 ,30,31,32 ,33,34] image-guided tumour delineation have been reported extensively elsewhere.…”