Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms

Abstract

Background No prominent advancements in osteosarcoma (OS) treatment have been made in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, the lack of targeted photosensitizers for OS treatment severely limits its applications. Results In this study, we constructed a potential theranostic nanoplatform by using (poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IR780 into the shell (PLGA-IR780 NPs), which were further camouflaged with human OS cell membranes from the HOS cell line (MH-PLGA-IR780 NPs). These constructed NPs showed the capacity for homologous targeting with excellent photoacoustic (PA)/fluorescence (FL) imaging ability. Benefitting from their homologous targeting capacity, MH-PLGA-IR780 NPs obviously promoted cell endocytosis in vitro and tumor accumulation in vivo, which could further improve PDT performance under near-infrared (NIR) irradiation. In addition, to their homologous targeting and PA/FL dual-mode imaging ability, MH-PLGA-IR780 NPs had advantages in penetrating deeper into tumor tissues and in real-time dynamic distribution monitoring in vivo, which laid a foundation for further clinical applications in OS. Moreover, we demonstrated that PDT guided by the constructed NPs could significantly induce HOS cells apoptosis and ferroptosis via excessive accumulation of reactive oxygen species (ROS), and further determined that the potential anticancer molecular mechanism of apoptosis was triggered by the release of cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and that ferroptosis caused the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and the inactivation of glutathione peroxidase 4 (GPX4), synergistically leading to excessive accumulation of Lipid-ROS and Lipid peroxides (LPOs). Concurrently, MH-PLGA-IR780 NPs-guided PDT also showed an obvious inhibitory effect on tumor growth in vivo. Conclusion These results suggest that this homologous targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and contributes a new and promising approach for OS therapy. Graphical Abstract

Cell membrane-camouflaged PLGA biomimetic system for diverse biomedical application

“…Innate lesion-homing capabilities of CM provide excellent drug delivery and multimodal diagnosis across varied fields, including cancer, immune diseases, and infectious diseases. For instance, integration of different mechanisms such as immunotherapy, light therapy, and ferroptosis can overcome tumor resistance (Wang et al., 2022b ). Notably, the bionic system with an increased surface area upon the coating on PLGA core is more conducive for exposure and stretching of antigen or receptor-binding protein and shows great talents in immunoregulation, anti-inflammatory, pathological molecular blockade, and nanosponge detoxification.…”

Combined Photodynamic and Photothermal Therapy and Immunotherapy for Cancer Treatment: A Review

“… MH-PLGA-IR780 NPs theranostic nanoplatform-guided PDT approach could contribute to PDT-mediated apoptosis and inhibit tumor growth in mouse xenografts. [ 173 ] PTT The mPDA NPs core endowed the mPDA@CMs NPs-CQ with good photothermal capability to mediate PTT killing of prostate cancer cells, while NIR-triggered CQ release from the nanosystem further arrested PTT-induced protective autophagy of cancer cells, thus weakening the resistance of prostate cancer cells to PTT. The mPDA@CMs NPs-CQ could induce significant autophagosome accumulation, ROS generation, mitochondrial damage, endoplasmic reticulum stress, and apoptotic signal transduction, which finally results in synergistic prostate tumor ablation in vivo.…”

Recent progress in cancer therapy based on the combination of ferroptosis with photodynamic therapy

“…Zhang et al have used sinoporphyrin sodium to study cholangiocarcinoma and confirmed that PDT alone downregulates the expression of the cystine/glutamate transporter (system x c -), thus inducing ferroptosis [41]. In addition, to enhance the therapeutic effect, Wang et al have used a polylactic acid-glycolic acid copolymer to load the photosensitizer IR780 (Figure 2) [42]. The micelle nanoparticles were then coated with human osteosarcoma cell membranes to obtain a biomimetic active targeting nanoplatform (MH-PLGA-IR780).…”