Evaluating Nanoshells and a Potent Biladiene Photosensitizer for Dual Photothermal and Photodynamic Therapy of Triple Negative Breast Cancer Cells

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.

Cancer Cell Membrane-Coated Nanoparticles for Cancer Management

“…The two main examples of this are photothermal therapy (PTT) and photodynamic therapy (PDT), and both have recently been explored in conjugation with membrane-wrapped NPs. In photothermal therapy, NPs with unique optical properties are delivered into tumors, which are then irradiated with near-infrared light that causes the NPs to produce heat capable of thermally damaging cancer cells [86][87][88][89][90][91][92]. Similarly, in PDT, photosensitizers are delivered into tumors, and subsequent irradiation of the tumor causes the photosensitizer to transfer the absorbed energy to adjacent tissue oxygen molecules, producing toxic singlet oxygen that destroys cancer cells [89].…”

“…In photothermal therapy, NPs with unique optical properties are delivered into tumors, which are then irradiated with near-infrared light that causes the NPs to produce heat capable of thermally damaging cancer cells [86][87][88][89][90][91][92]. Similarly, in PDT, photosensitizers are delivered into tumors, and subsequent irradiation of the tumor causes the photosensitizer to transfer the absorbed energy to adjacent tissue oxygen molecules, producing toxic singlet oxygen that destroys cancer cells [89]. While there are some examples of membrane-wrapped NPs being used strictly for PTT or PDT to treat cancer [70,[93][94][95][96][97][98], these singular treatments use non-cancer cell membranes.…”

Photodynamic Therapy Induced Cell Death Mechanisms in Breast Cancer

“…Photothermal therapy entails the use of nanoparticles or photosensitizers to induce cancer cell death by irradiation at electromagnetic radiation with preferably infrared wavelengths. This is an extension of the PDT approach and occurs when the PS or nanoparticle inside the tumor releases heat following irradiation with light at a specific wavelength [ 27 ]. Examples are given thereafter:…”

“…Riley and colleagues also observed a synergistic induction of cell death in MDA-MB-231 TNBC cells, using the combination of PDT and PTT. They observed that reduced doses of light induced apoptotic cell death [ 27 ].…”

Biomimetic Nanoparticles for the Treatment of Hematologic Malignancies

“…In PTT, materials embedded in tumors absorb externally applied light and convert it into heat to destroy cancer cells, whereas in PDT photosensitizers transfer absorbed light energy to adjacent ground‐state tissue oxygen molecules to produce toxic singlet oxygen. [ 63–65 ] To enable dual PDT/PTT treatment of Burkitt's lymphoma in mice, one group developed PM‐NPs coloaded with W 18 O 49 , a tungsten‐based photosensitizer, and Metformin (Met). [ 66 ] The rationale for this design was that the effectiveness of W 18 O 49 ‐mediated PDT and PPT has been limited by both rapid clearance and tumor hypoxia, which arises from a lack of oxygen associated with tumor progression and resistance to therapies.…”