Osteogenic and anti-tumor Cu and Mn-doped borosilicate nanoparticles for syncretic bone repair and chemodynamic therapy in bone tumor treatment

Abstract

Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge. The present therapeutic strategy concentrates on implanting bone substitutes for defect filling but suffers from failures in both enhancing bone regeneration and inhibiting the growth of tumor cells. Herein, Cu and Mn-doped borosilicate nanoparticles (BSNs) were developed for syncretic bone repairing and anti-tumor treatment, which can enhance bone regeneration through the osteogenic effects of Cu 2+ and Mn 3+ ions and meanwhile induce tumor cells apoptosis through the hydroxyl radicals produced by the Fenton-like reactions of Cu 2+ and Mn 3+ ions. In vitro study showed that both osteogenic differentiation of BMSCs and angiogenesis of endothelial cells were promoted by BSNs, and consistently the critical bone defects of rats were efficiently repaired by BSNs through in vivo evaluation. Meanwhile, BSNs could generate hydroxyl radicals through Fenton-like reactions in the simulated tumor microenvironment, promote the generation of intracellular reactive oxygen species, and eventually induce tumor cell apoptosis. Besides, subcutaneous tumors of mice were effectively inhibited by BSNs without causing toxic side effects to normal tissues and organs. Altogether, Cu and Mn-doped BSNs developed in this work performed dual functions of enhancing osteogenesis and angiogenesis for bone regeneration, and inhibiting tumor growth for chemodynamic therapy, thus holding a great potential for syncretic bone repairing and anti-tumor therapy.

Wireless electrical stimulation at the nanoscale interface induces tumor vascular normalization

“…Encouraged by the effective normalization of tumor blood vessels after wireless electrical stimulation treatment, we further evaluated the anti-tumor efficacy of P-BTO nanoparticles in combination with the chemotherapy drug DOX [ 57 ]. Tumor-bearing mice were divided randomly into eight groups: blank (saline), blank + LIPUS, P-BTO, P-BTO + LIPUS, DOX, DOX + LIPUS, P-BTO + DOX, and P-BTO + DOX + LIPUS.…”

A review on borate bioactive glasses (BBG): effect of doping elements, degradation, and applications

“…Similarly, it has been demonstrated that Cu-doped BGs and scaffolds promote endothelial cell proliferation and increase mesenchymal stem cell (MSC) differentiation levels. 118,119 To improve bone healing and anti-tumor therapy via the osteogenic properties of Cu, Libin et al 120 recently doped BBG nanoparticles with Cu. According to an in vitro study, the nanoparticle increased endothelial cell angiogenesis as well as the differentiation potential of bone marrow stromal cells (BMSCs).…”

A triphenylphosphine coordinated Cu(i) Fenton-like agent with ferrocene moieties for enhanced chemodynamic therapy

“…Compared with the traditional homo-metallic CDT agents, hetero-metallic Fenton-like centers have attracted increasing attention due to their excellent conversion efficiency for hydrogen peroxide. 11–18 Recently, ferrocene moieties with excellent redox properties have proved to be suitable for the CDT treatment strategy. 19–23 For example, Dong et al prepared a covalent organic framework (COF)-based ferrocene (Fc) and glutathione peroxidase 4 (GP × 4) inhibitor loaded nano drug RSL3@COF-Fc to enhance ˙OH-induced cellular damage by CDT.…”