Radiotherapy is an important regime for treating malignant tumors. There is interest in the development of radiosensitizers to increase the local treatment efficacy under a relatively low and safe radiation dose. In this study, we designed Au@Se-R/A nanocomposites (Au@Se-R/A NCs) as nano-radiosensitizer to realize synergistic radiochemotherapy based on the radiotherapy sensitization property of Au nanorods (NRs) and antitumor activity of Se NPs. In vitro studies show that the combined treatment of A375 melanoma cells in culture with NCs and X-ray induces cell apoptosis through alteration in expression of p53 and DNA-damaging genes and triggers intracellular ROS overproduction, leading to greatly enhanced anticancer efficacy. Further studies using clinically used radiotherapy equipment demonstrate that the combined treatment of NCs and X-ray significantly inhibits the tumor growth in vivo and shows negligible acute toxicity to the major organs. Taken together, this study provides a strategy for clinical translation application of nanomedicne in cancer radiochemotherapy.
An efficient radiotherapeutic agent is synthesized using ultrathin two-dimensional 30-nm-wide and 2-nm-thick Bi 2 Se 3 nanosheets (NSs) as a radiosensitizer. Chitosan (CS) and RGD peptide are employed to enhance the radiotherapy efficiency and biocompatibility. The Bi 2 Se 3 -CS-RGD NSs exhibit excellent targeting ability to αvβ3 integrin-overexpressing cancer cells and potent radiosensitization efficiency with high stability. Detailed in vitro experiments show that the Bi 2 Se 3 -CS-RGD NSs enhance the sensitivity of HeLa cells to X-ray-induced cell death by inhibiting TrxR activities and activating downstream reactive oxygen species-mediated signaling pathways. In vivo experiments using intravenous or intratumor injection demonstrate that the Bi 2 Se 3 -CS-RGD NSs are more efficient tumor growth inhibitors compared to bare Bi 2 Se 3 NSs. The multifunctionality of the NSs enables the use of photoacoustic imaging and magnetic resonance imaging to examine their targeting ability and therapeutic effects, respectively. In addition, the RGD-decorated Bi 2 Se 3 NSs show much better in vivo biocompatibility and can be efficiently expelled from the body after 48 h post injection. This study reveals an effective and safe theranostic agent for next-generation cancer radiotherapy.
The rational design of cancer‐targeted and bioresponsive drug delivery vehicles can enhance the anticancer efficacy of conventional chemotherapeutics and reduce their adverse side effects. However, the complexity of precise delivery and the ability to trigger drug release in specific tumor sites remain a challenging puzzle. Here, a sequentially triggered nanosystem composed of HER2 antibody with disulfide linkage as a surface decorator (HER2@NPs) is constructed for precise drug delivery and the simultaneous inhibition of cancer growth, migration, and invasion. The nanosystem actively accumulates in cancer cells, undergoes self‐immolative cleavage in response to biological thiols, and is degraded to form small nanoparticles. After internalization by receptor‐mediated endocytosis, the nanoparticles further disassemble under acidic conditions in the presence of lysozymes and cell lysates, leading to sequentially triggered drug release. The released payload triggers overproduction of reactive oxygen species and activates p53 and MAPKs pathways to induce cancer cell apoptosis. Moreover, HER2@NPs markedly suppress the migration and invasion of human bladder cancer cells at nontoxic concentrations. HER2@NPs demonstrate potent in vivo anticancer efficacy, but show no obvious histological damage to the major organs. Taken together, this study provides a valid tactic for the rational design of sequentially triggered nanosystems for precise drug delivery and cancer therapy.
Malignant pleural effusion (MPE) remains a treatment bottleneck in advanced lung cancer, due to its complicated microenvironments and “cold” immunity. Therefore, the search for therapeutic drugs to transform MPE to functionally “hot” one could advance the development of effective immunotherapeutic strategy. Herein, translational selenium nanoparticles coated with immune‐modulating macromolecule lentinan (SeNPs@LNT) are designed to restore the dysfunctional immune cells in patient‐derived MPE microenvironment. Internalization of the SeNPs@LNT can effectively reduce the immunosuppressive status by enhancing the proliferation of CD4+ T cells and natural killer cells, and remodeling the tumor associated macrophages into tumoricidal M1 phenotype in MPE derived from patients presenting low Se levels in blood and pleural effusion. Th1, cytotoxic T cell, γδ T, and B cell functions are upregulated, and Th2, Th17, and Treg cells activity is downregulated. Furthermore, SeNPs@LNT can be gradually metabolized into SeCys2 to promote the production of metabolites associated with tumor growth inhibition and immune response activation in MPE microenvironment. In contrast, lung cancer markers and vitamin B6 metabolism are decreased. The translational SeNP‐based nanotherapeutic strategy restores functional “cold” MPE to “hot” MPE to activate the immune responses of various immune cells in MPE of lung cancer patients.
Herein we synthesize an HER2 antibody-conjugated selenium nanoparticle platform can efficiently deliver both therapeutic agents and diagnostic agents (superparamagnetic iron oxide nanoparticles) across the BBB into the tumor tissues and enhances their effects on brain tumor treatment and MR imaging.
The rational design of a novel phycocyanin-based nanosystem with bio-responsive properties to achieve prolonged blood circulation and overcome drug resistance without causing systemic toxicity.
Bismuth telluride (Bi 2 Te 3 ) is an available thermoelectric material with the lowest band gap among bismuth chalcogenides, revealing a broad application in photocatalysis. Unfortunately, its size and morphology related to a radio-catalysis property have rarely been explored. Herein, an ethylenediaminetetraacetic acid (EDTA)-assisted hydrothermal strategy was introduced to synthesize polytypic Bi 2 Te 3 nanoplates (BT NPs) that exhibit sizedependent radio-sensitization and metabolism characteristics in vivo. By simply varying the molar ratio of EDTA/Bi 3+ during the reaction, BT NPs with different sizes and morphologies were obtained. EDTA acting as chelating agent and "capping" agent contributed to the homogeneous growth of BT NPs by eliminating dangling bonds and reducing the surface energy of different facets. Further analyzing the size-dependent radio-sensitization mechanism, largersized BT NPs generated holes that preferentially catalyzed the conversion of OH − to •OH when irradiated with X-rays, while the smaller-sized BT NPs exhibited faster decay kinetics producing higher 1 O 2 levels to enhance radiotherapy effects. A metabolomic analysis revealed that larger-sized BT NPs were oxidized into Bi(O x ) in the liver via a citrate cycle pathway, whereas smaller-sized BT NPs accumulated in the kidney and were excreted in urine in the form of ions by regulating the metabolism of glutamate. In a cervical cancer model, BT NPs combined with X-ray irradiation significantly antagonized tumor suppression through the promotion of apoptosis in tumor cells. Consequently, in addition to providing a prospect of BT NPs as an efficient radio-sensitizer to boost the tumor radiosensitivity, we put forth a strategy that can be universally applied in synthesizing metal chalcogenides for catalysis-promoted radiotherapy.
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