Abstract Mesoporous silica nanoparticles (MSNs) are emerging as one of the promising nanomaterials for biomedical applications, but the nanomaterials–body interaction exposed by different ...administration routes remained poorly understood. In the present study, a systematic investigation of the absorption, distribution, excretion and toxicity of silica nanoparticles (SNs) with the average size of 110 nm after four different exposure routes including intravenous, hypodermic, intramuscular injection and oral administration to mice were achieved. The results showed that a fraction of the SNs administrated by the intramuscular and hypodermic injection could cross different biological barriers into the liver but with a low absorption rate. Exposing by oral administration, SNs were absorbed into the intestinal tract and persisted in the liver. And SNs administrated by intravenous injection were mainly present in the liver and spleen. In addition, SNs could cause inflammatory response around the injection sites after intramuscular and hypodermic injection. It was also found that SNs were mainly excreted through urine and feces after different exposure routes. This study will be helpful for selecting the appropriate exposed routes for the development of nanomaterials-based drug delivery system for biomedical applications.
Recently, plasmonic copper sulfide (Cu2–x S) nanocrystals (NCs) have attracted much attention as materials for photothermal therapy (PTT). Previous reports have correlated photoinduced cell death to ...the photothermal heat mechanism of these NCs, and no evidence of their photodynamic properties has been reported yet. Herein we have prepared physiologically stable near-infrared (NIR) plasmonic copper sulfide NCs and analyzed their photothermal and photodynamic properties, including therapeutic potential in cultured melanoma cells and a murine melanoma model. Interestingly, we observe that, besides a high PTT efficacy, these copper sulfide NCs additionally possess intrinsic NIR induced photodynamic activity, whereupon they generate high levels of reactive oxygen species. Furthermore, in vitro and in vivo acute toxic responses of copper sulfide NCs were also elicited. This study highlights a mechanism of NIR light induced cancer therapy, which could pave the way toward more effective nanotherapeutics.
Abstract Mesoporous silica nanoparticles (MSNs) have been proven to be effective drug carriers for oral delivery. However, little attention has been paid to their in vivo biodistribution and toxicity ...after oral administration. The effect of particle shape on their in vivo behavior is also unknown. In this study, we systematically studied the acute toxicity and biodistribution of three types of MSNs with aspect ratios (ARs) of 1, 1.75 and 5 after oral administration. The effect of particle shape as a key physicochemical parameter of MSNs was discussed. With the increase of AR, MSNs showed decreased in vivo biodegradation, systematic absorption and excretion, especially decreased liver distribution and urinal excretion. During the period of urinal excretion, MSNs induced a shape-dependent renal damage including hemorrhage, vascular congestion and renal tubular necrosis. These findings will enrich the knowledge to rationally engineer bionanomaterials, and bring new insights into nanotoxicity. From the Clinical Editor Advances in nanotechnology have resulted in improvement in drug delivery, of which mesoporous silica nanoparticles have been used as carriers for oral drugs. Nonetheless, studies on their absorption, distribution, metabolism, excretion (ADME) and toxicity still need to be performed. In this article, authors evaluated the effects of particle size and shape on in vivo behavior. The findings would shine light on future design of future drug delivery systems.
Low targeting efficiency is one of the biggest limitations for nanoparticulate drug delivery system-based cancer therapy. In this study, an efficient approach for tumor-targeted drug delivery was ...developed with mesenchymal stem cells as the targeting vehicle and a silica nanorattle as the drug carrier. A silica nanorattle–doxorubicin drug delivery system was efficiently anchored to mesenchymal stem cells (MSCs) by specific antibody–antigen recognitions at the cytomembrane interface without any cell preconditioning. Up to 1500 nanoparticles were uploaded to each MSC cell with high cell viability and tumor-tropic ability. The intracellular retention time of the silica nanorattle was no less than 48 h, which is sufficient for cell-directed tumor-tropic delivery. In vivo experiments proved that the burdened MSCs can track down the U251 glioma tumor cells more efficiently and deliver doxorubicin with wider distribution and longer retention lifetime in tumor tissues compared with free DOX and silica nanorattle-encapsulated DOX. The increased and prolonged DOX intratumoral distribution further contributed to significantly enhanced tumor-cell apoptosis. This strategy has potential to be developed as a robust and generalizable method for targeted tumor therapy with high efficiency and low systematic toxicity.
Abstract Crystalline silica is well known to induce chronic lung inflammation by inhalation that can progress to silicosis. Recently, we reported that silica nanoparticles (SN) cause more damage to ...liver instead of lung when they enter the body by intravenous injection. However, this mechanism is still unclear. In the present study, liver damages caused by mesoporous hollow silica nanoparticles (MHSNs) were demonstrated after continuous intraperitoneal injection into mice twice a week for 6 weeks. The administration of MHSNs at 50 mg/kg increased liver injury markers in serum, such as alanine aminotransferase (ALT), inflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Histological analysis revealed lymphocytic infiltration and silicotic nodular like lesions in liver. Collagen fibers were observed around the silicotic nodular like lesion, and hydroxyproline level in liver was also increased dramatically. We also found that activated kupffer cells (KCs) played a key role in the liver damage caused by SNs similar to alveolar macrophage in the process of silicosis. These suggest that the mechanism of liver damage caused by SNs is in consonance with the occurrence of silicosis. These findings may provide useful information for the further toxicity and bioapplication research of nanoparticles.
Microwave sensitization nanoplatform, integrating multiple functional units for improving tumor selectivity, is of great significance for clinical tumor microwave treatment. Lanthanide europium metal ...organic framework (EuMOF) is expected to be a theranostic nanoplatform owing to its unique luminescent and microwave sensitization properties. However, it is difficult to be applied to complicated biological systems for EuMOF due to its rapid degradation induced by the solvent molecular and ionic environment. In this work, a luminescent EuMOF nanocomposite (EuMOF@ZIF/AP-PEG, named EZAP) was designed, which brought the multifunctional characteristics of microwave sensitization, fluorescence imaging and drug loading.
Lamellar EuMOF was synthesized by a hydrothermal method. Through the charge adsorption mechanism, the zeolite imidazole framework (ZIF) structure was intensively assembled on the surface of EuMOF to realize the protection. Then, through in-situ Apatinib drug loading and PEG modification, EZAP nanocomposite was finally obtained. Apatinib (AP) was a kind of chemotherapy drug approved by Food and Drug Administration for targeted therapy of tumors. PEG modification increased long-term circulation of EZAP nanocomposite. The physical and chemical structure and properties of EuMOF@ZIF (EZ) were systematically represented, indicating the successful synthesis of the nanocomposite. The toxic and side effects were negligible at a safe dose. The growth of human liver cancer cells and murine liver cancer cells in vitro was significantly inhibited, and the combined microwave-thermal therapy and chemotherapy in vivo achieved high anti-cancer efficacy. Moreover, EZAP nanocomposite possessed bright red fluorescence, which can be applied for tumor imaging in tumor-bearing mice in vivo.
Therefore, EZAP nanocomposite showed high microwave sensitization, excellent fluorescence properties and outstanding drug loading capacity, establishing a promising theranostic nanoplatform for tumor therapy and fluorescence imaging. This work proposes a unique strategy to design for the first time a multifunctional nanoplatform with lanthanide metal organic frameworks for biological applications in tumor therapy and diagnosis.
CdS@MoS
2
nanocomposites (NCs) were successfully prepared through a simple hydrothermal reaction. The morphology and structure of MoS
2
nanoflowers on CdS nanorods could be regulated by the change of ...the mass percentage of MoS
2
. The adsorption efficiency and photocatalytic activity of CdS@MoS
2
NCs were investigated by the adsorption and photocatalytic degradation of Rhodamine 6G. Interestingly, with the increase of MoS
2
ratio in the NCs, the adsorption effect of CdS@MoS
2
NCs increased significantly. These CdS@MoS
2
NCs showed a strong ability to process Rhodamine 6G, and could deal with up to 95% Rhodamine 6G within 1 h.
Graphical abstract
CdS@MoS
2
nanocomposites with tunable shape were synthesized through a hydrothermal method and possess high performance in the removal of Rhodamine 6G
Purpose: P-glycoprotein (P-gp), which is highly expressed in liver cancer cells, is one of the obstacles for the treatment of cancer. In this study, we have prepared and characterized a kind of novel ...ICG&Cur@MoS2 (ICG and Cur represent indocyanine green and curcumin, respectively) nanoplatform, which can achieve photothermal-photodynamic therapy and inhibit the P-gp effectively and safely. Methods: In this work, plenty of studies including drug release, acute toxicity, Western blot, real-time PCR, cell viability, therapeutic experiment in vivo, immunofluorescence and so on were conducted to test the antitumor potential of ICG&Cur@MoS2 and the inhibitory effect of curcumin on P-gp. Results: The ICG&Cur@MoS2 NPs exhibit an excellent photothermal effect and relatively low toxicity. Cell viability in the ICG&Cur@MoS2 + NIR group was significantly lower than that in ICG@MoS2 + NIR group (75.3% vs 81.2%, 59.0% vs 64.4%, 20.3% vs 27.5%, and 15.4% vs 22.3%) at the concentration of ICG at 0.5, 5, 25, 50 μg/mL (P< 0.05 at each concentration). Western blot, Q-PCR, and immunofluorescence assay indicate ICG&Cur@MoS2 NPs can inhibit the P-gp effectively and safely. In vivo, the tumors in the ICG@MoS2 + NIR group are significantly smaller than those in the MoS2 + NIR group (95.0 vs 420.9 mm3, p< 0.05). Conclusion: In conclusion, we have successfully synthesized ICG&Cur@MoS2 nanoparticles which can not only achieve PTT-PDT but also inhibit P-gp effectively. Our findings indicate that the PTT-PDT exhibits great potential in the treatment of hepatocellular carcinoma. Meanwhile, ICG&Cur@MoS2 can effectively inhibit the expression of P-gp, which will enhance the PDT effect.
Nanoscale ZIF-8 had a high inhibitory effect on pyruvate kinase of M2.
Display omitted
Tumor cells usually show abnormally high glycolysis rate to maintain the dynamic balance of energy. The growth ...of tumor cells can be affected by inhibiting the activity of pyruvate kinase (especially M2-type isozyme, PKM2), the rate limiting enzyme of glycolysis. This is helpful to the treatment of tumor. Herein, metal organic frameworks (MOFs) were found to inhibit the activity of PKM2. Nanoscale ZIF-8 was synthesized by standing and ultrasonic method, respectively. The ZIF-8 has the performance of inhibiting PKM2. Further research showed that the inhibition ability was attributed to zinc ion in ZIF-8. Interestingly, the IC50 of ZIF-8 on PKM2 was one percent of that of zinc ion. This novel enzyme inhibitor is expected to be used in cancer therapy.
Cancer, as one of the most attention‐grabbing medical problems, has been tried to solve with various methods. With the development of nanotechnology, diagnosis and therapy based on nanoplatforms have ...become new dawn for overcoming cancer problems. Biocompatible nanoplatforms integrating diagnosis and therapy technology for cancer have been extensively studied. Most of the reported works focus on the diagnosis and therapy of subcutaneous tumor. To promote clinical application, it is of great significance to develop efficient methods for deep tumors. This work reviews the latest research progress and future development prospects for the diagnosis and therapy of deep tumors based on biocompatible nanoplatforms. It mainly introduces four cancer diagnostic technologies (fluorescence imaging (FI), computed tomography (CT), magnetic resonance imaging (MRI), and photoacoustic imaging (PAI)) and four tumor treatment methods (phototherapy, ultrasound therapy, radiotherapy (RT), and microwave therapy (MWT)) based on the nanoplatforms. Several diagnostic techniques and treatment methods are systematically summarized and compared, and the advantages and limitations of different methods in tumors are discussed. At last, the application prospects and challenges of the nanoplatforms for the diagnosis and therapy of deep tumors are discussed. It is hoped that this review will provide some useful information for the research in this field.
SCHEME 1. An overview of emerging biocompatible nanoplatforms in diagnosis and therapy. The diagnostic techniques include PI, CT, MRI, and PAI. The treatment methods include phototherapy, ultrasound therapy, RT and MWT.
PDF
