Mitochondria‐Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer

Abstract

Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual-modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria-targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria-targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy.

Multistage Targeting Strategy Using Magnetic Composite Nanoparticles for Synergism of Photothermal Therapy and Chemotherapy

“…The surface potential of Fe@PDA–TPP/SS/DOX increased from +4 to +18 mV after it was treated with 10 × 10 −3 m GSH at pH 7.4 for 6 h, which was probably caused by the breakage of disulfide bonds and exposure of TPP. The positively charged TPP can mediate mitochondrial targeting . The UV–vis absorption spectrum also showed the changes in the nanoparticles during the synthesis (Figure F).…”

“…Organelles inside mammalian cells are the molecular targets of many drugs . Compared with simple diffusion and random interaction of chemical drugs and photosensitizers in cancer cells, therapeutic efficacy can be enhanced considerably if the chemical drugs and PTT agents are specifically delivered to the targeted organelle, especially the mitochondria . Mitochondria are not only vital cellular organelles to supply energy for cells, but also crucial regulators of cell apoptosis .…”

Dye‐Anchored MnO Nanoparticles Targeting Tumor and Inducing Enhanced Phototherapy Effect via Mitochondria‐Mediated Pathway

“…These works indicated that mitochondrial targeting was an effective strategy in oncotherapy. Hence, mitochondria‐targeting phototherapy has emerged as an attractive supplementary to oncotherapy …”

Hyaluronic acid-coated chitosan nanoparticles induce ROS-mediated tumor cell apoptosis and enhance antitumor efficiency by targeted drug delivery via CD44

“…In recent years, numerous studies confirmed the role of NPs in enhancing the accumulation of drugs at the tumor site and controlling the drug release rate to prolong curing times [16–18]. Furthermore, related studies showed how the internalization of some NPs increased the generation of reactive oxygen species (ROS) and enhanced synergistic antitumor efficacy by activating mitochondria-meditated apoptosis [19–22]. To investigate whether drug-loaded NPs could induce more cell apoptosis, and to further determine whether NPs activated the ROS-mediated mitochondrial apoptosis pathway, we designed HA-coated chitosan (CS) NPs to enhance antitumor efficiency via targeted drug delivery by way of the interactions between HA and CD44.…”