Abstract
Light-activated therapies are ideal for treating cancer because they are non-invasive and highly specific to the area of light application. Photothermal therapy (PTT) and photodynamic therapy (PDT) are two types of light-activated therapies that show great promise for treating solid tumors. In PTT, nanoparticles embedded within tumors emit heat in response to laser light that induces cancer cell death. In PDT, photosensitizers introduced to the diseased tissue transfer the absorbed light energy to nearby ground state molecular oxygen to produce singlet oxygen, which is a potent reactive oxygen species (ROS) that is toxic to cancer cells. Although PTT and PDT have been extensively evaluated as independent therapeutic strategies, they each face limitations that hinder their overall success. To overcome these limitations, we evaluated a dual PTT/PDT strategy for treatment of triple negative breast cancer (TNBC) cells mediated by a powerful combination of silica core/gold shell nanoshells (NSs) and palladium 10,10-dimethyl-5,15-bis(pentafluorophenyl)biladiene-based (Pd[DMBil1]-PEG750) photosensitizers (PSs), which enable PTT and PDT, respectively. We found that dual therapy works synergistically to induce more cell death than either therapy alone. Further, we determined that low doses of light can be applied in this approach to primarily induce apoptotic cell death, which is vastly preferred over necrotic cell death. Together, our results show that dual PTT/PDT using silica core/gold shell NSs and Pd[DMBil1]-PEG750 PSs is a comprehensive therapeutic strategy to non-invasively induce apoptotic cancer cell death.
Highlights
Light-activated therapies offer less invasive, more precise, and safer alternatives for cancer treatment than conventional therapies such as chemotherapy, surgery, and radiation
The hydrodynamic diameter of poly(ethylene glycol) (PEG)-NSs remained the same even with Pd[DMBil1]-PEG750 combined into the solution, demonstrating that PEG-NSs are not complexed with the photosensitizers (Figure 2a)
This was important because dual Photothermal therapy (PTT)/photodynamic therapy (PDT) requires that each agent retain its individual optical properties to be effective
Summary
Light-activated therapies offer less invasive, more precise, and safer alternatives for cancer treatment than conventional therapies such as chemotherapy, surgery, and radiation. In light-activated therapies, photoresponsive materials are intravenously injected into the body and accumulate within tumor tissue via the enhanced permeability and retention (EPR) effect, whereby the administered materials achieve high intratumoral concentrations due to the leaky vasculature and poorly organized lymphatic system characteristic of tumors [1,2]. Due to the benefits afforded by light-activated therapies, photoresponsive materials have been developed to elicit a number of therapeutic effects including drug and gene delivery, hyperthermia, or the production of reactive oxygen species or other cytotoxic radicals [3,4,5,6,7]. The success of light-activated therapies depends on the sufficient intratumoral accumulation of the photoresponsive materials (while maintaining minimal off-target dark toxicity), as well as on tumor physiology. A promising strategy to ensure complete tumor eradication would be to combine different types of light-activated therapies to harness the multiple discrete benefits associated with the use of light for cancer treatment while minimizing the limitations of any individual therapy
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