Abstract
Sonodynamic therapy (SDT) has emerged as an important modality for cancer treatment. SDT utilizes ultrasound excitation, which overcomes the limitations of light penetration in deep tumors, as encountered by photodynamic therapy (PDT) which uses optical excitations. A comparative study of these modalities using the same sensitizer drug can provide an assessment of their effects. However, the efficiency of SDT and PDT is low in a hypoxic tumor environment, which limits their applications. In this study, we report a hierarchical nanoformulation which contains a Food and Drug Administration (FDA) approved sensitizer chlorin, e6, and a uniquely stable high loading capacity oxygen carrier, perfluoropolyether. This oxygen carrier possesses no measurable cytotoxicity. It delivers oxygen to overcome hypoxia, and at the same time, boosts the efficiency of both SDT and PDT. Moreover, we comparatively analyzed the efficiency of SDT and PDT for tumor treatment throughout the depth of the tissue. Our study demonstrates that the strengths of PDT and SDT could be combined into a single multifunctional nanoplatform, which works well in the hypoxia environment and overcomes the limitations of each modality. The combination of deep tissue penetration by ultrasound and high spatial activation by light for selective treatment of single cells will significantly enhance the scope for therapeutic applications.
Highlights
Two closely related cancer therapeutic approaches, photodynamic therapy (PDT) and sonodynamic therapy (SDT), offer tumor destruction with unsurpassed anatomical precision
We introduce an integrated nanoplatform towards unified implementation of PDT and SDT under hypoxia
With a promising integration of high 3D precision of photoexcitation, deep penetration of ultrasound, and effective generation of reactive oxygen species (ROS) boosted by oxygen delivery, this unified nanoplatform presents an intriguing avenue for expanding the capabilities of PDT and SDT
Summary
Two closely related cancer therapeutic approaches, photodynamic therapy (PDT) and sonodynamic therapy (SDT), offer tumor destruction with unsurpassed anatomical precision. Recent approaches include oxygenation by a hydrogen peroxide (H2O2) catalysis [46,47] and oxygen delivery using hemoglobin [48,49] While these early studies have shown a significant potential of oxygenation for PDT and SDT, the efficiency of currently available nanoformulations is not sufficiently high, due to the limited amount of H2O2 in the tumor microenvironment and the inadequate oxygen loading capacity of hemoglobin [50]. To overcome this limitation, highly efficient perfluorocarbon (perfluorobutane, perfluoropentane, perfluorohexane, etc.)-based carriers have been tested [43]. With a promising integration of high 3D precision of photoexcitation, deep penetration of ultrasound, and effective generation of ROS boosted by oxygen delivery, this unified nanoplatform presents an intriguing avenue for expanding the capabilities of PDT and SDT
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