Combined chemo-immuno-photothermal therapy based on ursolic acid/astragaloside IV-loaded hyaluronic acid-modified polydopamine nanomedicine inhibiting the growth and metastasis of non-small cell lung cancer.

Combining chemotherapy and immunotherapy is a promising strategy for the treatment of non-small cell lung cancer (NSCLC) metastasis. However, platinum-based chemotherapeutics and immune checkpoint blockade-based cancer immunotherapy have toxic side effects and limitations. Ursolic acid (UA) and astragaloside IV (AS-IV) are natural compounds with anticancer activity sourced from Traditional Chinese medicine (TCM). However, their poor water solubilities and targeted deletions limit their medicinal value. In this study, we fabricated hyaluronic acid (HA)-modified UA/(AS-IV)-loaded polydopamine (PDA) nanomedicine (UA/(AS-IV)@PDA-HA) with a high yield at a low cost via simple synthesis. This represents a novel multifunctional nanomedicine that combines chemotherapy, photothermal therapy (PTT), and immunotherapy with an active tumor-targeting ability. The as-prepared nanomedicine not only increased the aqueous solubilities of UA and AS-IV, but also improved their active targeting abilities. HA binds specifically to the overexpressed cluster of differentiation 44 (CD44) on the surface of most cancer cells, thereby improving drug targeting. While evaluating the anticancer effect of UA/(AS-IV)@PDA-HA in vitro and in vivo, the PDA nanodelivery system significantly improved UA-mediated cytotoxicity and anti-metastatic ability against NSCLC cells. In addition, the system also improved the AS-IV-mediated self-immune response of tumor-related antigens, which further inhibited the growth and distant metastasis of NSCLC. Further, PDA nanomaterial-mediated PTT inhibited tumor growth substantially. UA/(AS-IV)@PDA-HA not only significantly eradicated the primary tumor but also strongly inhibited the distant metastasis of NSCLC in vitro and in vivo. Thus, it has immense potential for development as an efficient anti-metastatic agent for NSCLC.

Synergistic chemo-photothermal and ferroptosis therapy of polydopamine nanoparticles for esophageal cancer.

Aim: To develop synergistic chemo-photothermal and ferroptosis therapy nanoparticles to improve the efficacy of treatment for esophageal cancer. Materials & methods: Fe3O4@PDA-HCPT nanoparticles (NPs) were constructed and characterized. Their synergistic antitumor effects were evaluated in EC1 and EC109 esophageal cancer cells as well as in esophageal cancer-bearing mice. Results: In vitro and in vivo experiments showed that Fe3O4@PDA-HCPT NPs exhibited significant tumor inhibition and excellent diagnostic properties. The killing ability of tumor cells was significantly enhanced after irradiation. Conclusion: Synergistic application of the three therapies effectively inhibited tumor growth and exhibited potent antitumor effects, providing strong support for developing nanoparticles with synergistic antitumor effects of multiple therapies.

Synergistic treatment with multiple therapies has been shown to be a promising strategy for cancer treatment. Here, the authors designed Fe₃O₄@PDA-HCPT NPs composed of Fe₃O₄, polydopamine and the chemotherapy drug 10-hydroxycamptothecin. The authors achieved synergistic antitumor treatment with chemo-photothermal and ferroptosis therapy guided by T2-weighted MRI. In vitro and in vivo experiments showed that Fe₃O₄@PDA-HCPT NPs exhibited significant tumor inhibition and excellent diagnostic properties, which supports the development of relevant synergistic tumor therapies.

Camptothecin-Loaded and Manganese Dioxide-Coated Polydopamine Nanomedicine Used for Magnetic Resonance Imaging Diagnosis and Chemo-Photothermal Therapy for Lung Cancer.

Introduction: Camptothecin (CPT) is a cytotoxic quinolone alkaloid (isolated from a traditional Chinese medicine Camptotheca acuminata), used for the treatment of various malignancies, which inhibits DNA topoisomerase I (Topo I). However, its drawbacks, such as poor water solubility, stability, and highly toxic side effects, limit its clinical application. Therefore, CPT needs to be prepared as a nanomedicine to improve solubility, reduce side effects, and synergize with other therapies to improve efficacy. Methods: In this work, we constructed CPT NPs (nanoparticles), which were CPT-loaded and manganese dioxide (MnO2)-coated polydopamine (PDA) nanomedicine. In vitro, we explored the antitumor effect including CPT NPs-induced cell proliferation inhibition, apoptosis and ferroptosis for tumor cell lines. In vivo, we established LLC tumor-bearing mice model to evaluate their tumor imaging and anticancer effects. Results: CPT NPs improve the water solubility and stability of CPT and reduce its toxic effects. It has good biocompatibility, excellent photothermal conversion ability for photothermal therapy (PTT) and pH release in the tumor microenvironment. It can inhibit tumor cell proliferation, induce apoptosis and result in ferroptosis of tumor cells. More significantly, this nanomedicine can provide information for the location and diagnosis of tumors via magnetic resonance imaging. In general, the nanomedicine integrated with diagnosis and treatment has excellent anticancer effect. Discussion: Altogether, this nanomedicine possesses the ability to diagnose and therapy through magnetic resonance imaging and chemo-photothermal therapy, respectively. In addition, the integrated diagnosis and treatment nanomedicine has potential clinical application prospects through treating lung cancer with high efficiency and low side effect. It can support the construction of related nano-delivery systems.