ABSTRACT
Osteoclast hyperactivation stands as a significant pathological factor contributing to the emergence of bone disorders driven by heightened oxidative stress levels. The modulation of the redox balance to scavenge reactive oxygen species emerges as a viable approach to addressing this concern. Selenoproteins, characterized by selenocysteine (SeCys2) as the active center, are crucial for selenium-based antioxidative stress therapy for inflammatory diseases. This study reveals that surface-active elemental selenium (Se) nanoparticles, particularly lentinan-Se (LNT-Se), exhibit enhanced cellular accumulation and accelerated metabolism to SeCys2, the primary active Se form in biological systems. Consequently, LNT-Se demonstrates significant inhibition of osteoclastogenesis. Furthermore, in vivo studies underscore the superior therapeutic efficacy of LNT-Se over SeCys2, potentially attributable to the enhanced stability and safety profile of LNT-Se. Specifically, LNT-Se effectively modulates the expression of the selenoprotein GPx1, thereby exerting regulatory control over osteoclastogenesis inhibition, and the prevention of osteolysis. In summary, these results suggest that the prompt activation of selenoproteins by Se nanoparticles serves to suppress osteoclastogenesis and pathological bone loss by upregulating GPx1. Moreover, the utilization of bioactive Se species presents a promising avenue for effectively managing bone disorders.
Subject(s)
Nanoparticles , Osteoclasts , Osteogenesis , Selenium , Selenoproteins , Animals , Selenium/chemistry , Selenium/pharmacology , Mice , Osteogenesis/drug effects , Nanoparticles/chemistry , Selenoproteins/metabolism , Osteoclasts/metabolism , Osteoclasts/drug effects , Osteoclasts/cytology , Glutathione Peroxidase GPX1 , RAW 264.7 Cells , Glutathione Peroxidase/metabolism , Osteolysis/metabolism , Osteolysis/drug therapy , Osteolysis/pathologyABSTRACT
Bone metastasis is the major cause of cancer-related morbidity and mortality. To avoid further osteolysis, current treatment ideas focus on tumor cell and the inhibition of osteoclast. Herein, zeolitic imidazolate framework-8-capped Cu2-XSe composite nanoplatform (ICG@Cu2-XSe-ZIF-8) is developed for chemodynamic therapy (CDT) and photothermal therapy (PTT) treatment of malignant breast cancer bone tumors. The rational design of ZIF-8 encapsulation greatly reduces the accumulation of Cu2-XSe to damage the normal cells. Under acidic microenvironment in tumor, ZIF-8 is cleaved to release Cu2-XSe, which can subsequently degrade into Cu (+) and Cu (2+) ions to initiate a Fenton-like reaction inducing CDT. Meanwhile, Cu2-XSe is used to be an effective photothermal transduction agent for exerting the PTT effect. What's more, the selenium element in Cu2-XSe can regulates selenoprotein to inhibit tumor cells and osteoclasts. Of note, the hyperthermia induced by PTT can further enhance the CDT effect in tumor, achieving a synergistic PTT/CDT effect. Based on these advantages, ICG@Cu2-XSe-ZIF-8 effectively suppresses the tumor cells in bone tissue, and reduces the erosion of bone tissue via suppressing osteoclastogenesis. In conclusion, this study demonstrates the potential action mechanism of ZIF-8-capped nanomedicine against osteolysis in bone metastasis.
Subject(s)
Bone Neoplasms , Breast Neoplasms , Hyperthermia, Induced , Metal-Organic Frameworks , Nanoparticles , Osteolysis , Bone Neoplasms/drug therapy , Breast Neoplasms/drug therapy , Cell Line, Tumor , Female , Humans , Metal-Organic Frameworks/therapeutic use , Osteogenesis , Osteolysis/drug therapy , Tumor MicroenvironmentABSTRACT
BACKGROUND: The design of stable and biocompatible black phosphorus-based theranostic agents with high photothermal conversion efficiency and clear mechanism to realize MRI-guided precision photothermal therapy (PTT) is imminent. RESULTS: Herein, black phosphorus nanosheets (BPs) covalently with mono-dispersed and superparamagnetic ferrous selenide (FeSe2) to construct heteronanostructure nanoparticles modified with methoxy poly (Ethylene Glycol) (mPEG-NH2) to obtain good water solubility for MRI-guided photothermal tumor therapy is successfully designed. The mechanism reveals that the enhanced photothermal conversion achieved by BPs-FeSe2-PEG heteronanostructure is attributed to the effective separation of photoinduced carriers. Besides, through the formation of the P-Se bond, the oxidation degree of FeSe2 is weakened. The lone pair electrons on the surface of BPs are occupied, which reduces the exposure of lone pair electrons in air, leading to excellent stability of BPs-FeSe2-PEG. Furthermore, the BPs-FeSe2-PEG heteronanostructure could realize enhanced T2-weighted imaging due to the aggregation of FeSe2 on BPs and the formation of hydrogen bonds, thus providing accurate PTT guidance and generating hyperthermia to inhabit tumor growth under NIR laser with negligible toxicity in vivo. CONCLUSIONS: Collectively, this work offers an opportunity for fabricating BPs-based heteronanostructure nanomaterials that could simultaneously enhance photothermal conversion efficiency and photostability to realize MRI-guided cancer therapy.
Subject(s)
Ferrous Compounds/chemistry , Magnetic Resonance Imaging/methods , Nanoparticles/chemistry , Phosphorus/chemistry , Phosphorus/pharmacology , Photothermal Therapy/methods , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Female , Humans , Hyperthermia, Induced , Mice , Nanostructures , Phototherapy/methods , Polyethylene Glycols/chemistry , Precision MedicineABSTRACT
The search for chemotherapeutic drugs with a high efficiency and low toxicity continues to be a challenge in tumor treatment for scientists. Organometallic supramolecular polymers are an attractive option to achieve this goal, not only due to the fact that they possess both advantages of metal complexes and nanostructures but also because they are usually sensitive to pH. Here, we report the design and synthesis of a series novel smart microenvironment-responsive organocopper(II) supramolecular polymers with various substituted ligands to regulate their stability and anticancer efficacy. The investigation of the possible mechanisms revealed that the organocopper(II) polymers enter cancer cells through endocytosis and then induce apoptosis of cancer cells. Furthermore, the in vivo anticancer efficacy study demonstrated that these organocopper(II) polymers inhibited the tumor growth effectively without damage to the major organs. Overall, the organocopper(II) supramolecular polymers present a promising pathway to achieve high-efficiency and low-toxicity chemotherapy.
Subject(s)
Antineoplastic Agents/pharmacology , Coordination Complexes/pharmacology , Copper/pharmacology , Melanoma, Experimental/drug therapy , Polymers/pharmacology , Skin Neoplasms/drug therapy , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Copper/chemistry , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Humans , Macromolecular Substances/chemical synthesis , Macromolecular Substances/chemistry , Macromolecular Substances/pharmacology , Male , Melanoma, Experimental/pathology , Mice , Mice, Nude , Models, Molecular , Particle Size , Polymers/chemistry , Skin Neoplasms/pathology , Surface Properties , ViscosityABSTRACT
The successful clinical application of the three generation platinum anticancer drugs, cisplatin, carboplatin and oxaliplatin, has promoted research interest in metallodrugs; however, the problems of drug resistance and adverse effects have hindered their further application and effects. Thus, scientists are searching for new anticancer metallodrugs with lower toxicity and higher efficacy. The ruthenium complexes have emerged as the most promising alternatives to platinum-based anticancer agents because of their unique multifunctional biochemical properties. In this review, we first focus on the anticancer applications of various ruthenium complexes in different signaling pathways, including the mitochondria-mediated pathway, the DNA damage-mediated pathway, and the death receptor-mediated pathway. We then discuss the functionalization and cancer-targeting designs of different ruthenium complexes in conjunction with other therapies such as photodynamic therapy, photothermal therapy, radiosensitization, targeted therapy and nanotechnology for precise cancer therapy. This review will help in designing and accelerating the research progress regarding new anticancer ruthenium complexes.
Subject(s)
Antineoplastic Agents/chemistry , Coordination Complexes/chemistry , Ruthenium/chemistry , Animals , Antineoplastic Agents/therapeutic use , Coordination Complexes/therapeutic use , Drug Discovery , Humans , Molecular Structure , Molecular Targeted Therapy , Nanoparticles/chemistry , Photochemotherapy/methods , Precision Medicine , Structure-Activity RelationshipABSTRACT
A biocompatible ruthenium polypyridyl complex has been rationally designed and synthesized, which self-assembles into nanoparticles in aqueous solution to enhance the water solubility and biocompatibility. When activated by X-rays, the nanostructure synergistically triggers ROS overproduction in cancer cells to induce mitochondrial dysfunction and cell cycle arrest, thus realizing simultaneous chemo-radiotherapy.
