Mitochondrial-targeted multifunctional mesoporous Au@Pt nanoparticles for dual-mode photodynamic and photothermal therapy of cancers

Abstract

In the conventional non-invasive cancer treatments, such as photodynamic therapy (PDT) and photothermal therapy (PTT), light irradiation is precisely focused on tumors to induce apoptosis via the generation of reactive oxygen species (ROS) or localized heating. However, overconsumption of oxygen and restricted diffusion distance of ROS limit the therapeutic effects on hypoxic tumors. Herein, we developed a platform for the rapid uptake of multifunctionalized Au@Pt nanoparticles (NPs) by mitochondria in cancer cells. The mesoporous Au@Pt nanoparticles were labeled with a cell-targeting ligand (folic acid), a mitochondria-targeting group (triphenylphosphine (TPP)), and a photosensitizer (Ce6). This led to significant improvement of the PDT efficacy due to an enhanced cellular uptake, an effective mitochondrial ROS burst, and a rapid intelligent release of oxygen. Moreover, Au@Pt NPs can convert laser radiation into heat, resulting in thermally induced cell damage. This nanosystem could be used as a dual-mode phototherapeutic agent for enhanced cancer therapy and molecular targets associated with disease progression. We achieved a mitochondria-targeted multifunctional therapy strategy (a combination of PDT and PTT) to substantially improve the therapeutic efficiency.

Oxygen‐Evolving Mesoporous Organosilica Coated Prussian Blue Nanoplatform for Highly Efficient Photodynamic Therapy of Tumors

“…The PB@PMO and PB@PMO‐Ce6 also show the Si—O—Si vibration peak at 1050 cm −1 , C—S band at 650 cm −1 , and C—H band at 2900 cm −1 ,21, 30 confirming that the PB nanoparticles are successfully coated with PMO shells. The C=O vibration peak at 1700 cm −1 in PB@PMO‐Ce6 further indicates successful Ce6 conjugation (Figure 1f) 31, 32, 33. Nitrogen adsorption–desorption isotherms of the PB@PMO presented a typical IV curve, suggesting the mesoporous structure of the PMO shells (Figure S2a, Supporting Information).…”

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

“…Our hypothesis that combining PTT and PDT will synergistically improve the efficacy of each treatment stems from previous studies that evaluated other photoresponsive materials for dual therapies [ 29 , 30 , 31 , 32 , 33 ]. For example, NIR-absorbing NPs have been used as carriers for PSs tethered to their surfaces, which allows these conjugates to mediate PDT and PTT simultaneously [ 33 , 34 ].…”

Biodegradable hollow mesoporous organosilica nanotheranostics (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer

“…As it is well-known, ROS are inevitable products of cell metabolism, while high levels of intracellular ROS could attack mitochondria and cause mitochondrial-damage-dependent apoptosis [ 42 ]. Accumulating studies had proved that NIR-mediated PTT&PDT could induce the outbreak of ROS, following by activating oxidative stress and mediating mitochondrial damage in cancer cells [ 15 , 16 , 43 ]. As it has been demonstrated in the CCK-8 results, HMON@CuS/Gd did induce obvious anti-tumor cell death, partly contributed by their PDT effect.…”

“…Near infrared light (NIR)-based photo-therapy (PT) has been preferred for tumors targeting treatment, due to the advantages of minimal harm to normal tissues, non-invasiveness, and efficient therapeutic abilities [ 13 , 14 ]. Emerging studies have also identified that with the assistance of NIR, photosensitizers could increase the production of ROS to cause mitochondria-depended cancer cell death [ 15 – 17 ]. To some extent, the combination of photo-thermal therapy (PTT) and photo-dynamic therapy (PDT) could achieve much better therapeutic efficiency, as hyperthermia has been reported with the ability to elevate the level of oxygen in the tumor due to the increase of blood flow [ 18 , 19 ], thus overcoming the hypoxia-associated resistance for PDT.…”