Ultra-small Pyropheophorbide-a Nanodots for Near-infrared Fluorescence/Photoacoustic Imaging-guided Photodynamic Therapy

Abstract

Rationale: Nanoparticles (NPs) that are rapidly eliminated from the body offer great potential in clinical test. Renal excretion of small particles is preferable over other clearance pathways to minimize potential toxicity. Thus, there is a significant demand to prepare ultra-small theranostic agents with renal clearance behaviors.Method: In this work, we report a facile method to prepare NPs with ultra-small size that show renal clearable behavior for imaging-guided photodynamic therapy (PDT). Pyropheophorbide-a (Pa), a deep red photosensitizer was functionalized with polyethylene glycol (PEG) to obtain Pa-PEG. The prepared NPs formed ultra-small nanodots in aqueous solution and showed red-shifted absorbance that enabling efficient singlet oxygen generation upon light irradiation.Results: In vitro studies revealed good photodynamic therapy (PDT) effect of these Pa-PEG nanodots. Most of the cancer cells incubated with Pa-PEG nanodots were destroyed after being exposed to the irradiated light. Utilizing the optical properties of such Pa-PEG nanodots, in vivo photoacoustic (PA) and fluorescence (FL) imaging techniques were used to assess the optimal time for PDT treatment after intravenous (i.v.) injection of the nanodots. As monitored by the PA/FL dual-modal imaging, the nanodots could accumulate at the tumor site and reach the maximum concentration at 8 h post injection. Finally, the tumors on mice treated with Pa-PEG nanodots were effectively inhibited by PDT treatment. Moreover, Pa-PEG nanodots showed high PA/FL signals in kidneys implying these ultra-small nanodots could be excreted out of the body via renal clearance.Conclusion: We demonstrated the excellent properties of Pa-PEG nanodots that can be an in vivo imaging-guided PDT agent with renal clearable behavior for potential future clinical translation.

Photophysical Properties of Protoporphyrin IX, Pyropheophorbide-a, and Photofrin® in Different Conditions

“…Pyropheophorbide-a (PPa) is a natural second-generation bacteriochlorin PS which presents a significant absorption in the far-red spectral region and high 1 O 2 formation upon light illumination, suggesting it for PDT [ 28 , 29 ].…”

Nanomaterials for Chronic Kidney Disease Detection

“…An effective accumulation at the tumor site and obtaining the maximum concentration eight hours after injection were noted as the superiorities of this method. Furthermore, the high PA and fluorescent signal from the kidney tissues demonstrated their renal excretion [65] (Figure 2).…”

Recent Advances in Photosensitizers as Multifunctional Theranostic Agents for Imaging-Guided Photodynamic Therapy of Cancer

“…In another study, a biocompatible PEGylated nanoliposomes co-encapsulating clinically approved Iodinated CTIA iodixanol (Visipaque®) and a PS TPPS4 demonstrated enhanced PDT guided by CT imaging 201 . Similarly, many other nanoformulations combing heavy element and PS have been reported as a promising agent for CT imaging combined with PDT 86 , 202 - 208 .…”

“…These nanodots showed efficient cancer cell targeting, for simultaneous PAI and PDT 85 . Also, ultra-small pyropheophorbide-a-PEG nanodots were reported for PAI/FLI-guided PDT with effective renal clearance properties without any long-term side effects 86 . PS sinoporphyrin sodium loaded PEGylated graphene oxide reported by Yan et al, also exhibited great potential for enhanced FL/PA dual-modal imaging-guided synergistic PDT and photothermal therapy (PTT) in human adenocarcinoma mice model 87 .…”