Yuanyuan You

Functionalized halloysite nanotube by chitosan grafting for drug delivery of curcumin to achieve enhanced anticancer efficacy

Halloysite nanotubes (HNTs) have a unique tubular structure in nanoscale, and have shown potential as novel carriers for various drugs. Coating the nanotubes with a hydrophilic polymer shell can significantly decrease the toxicity and provide colloidal stability during blood circulation. Here, we synthesized chitosan grafted HNTs (HNTs-g-CS) and investigated their potential as a nano-formulation for the anticancer drug curcumin. The structure and properties of HNTs-g-CS were characterized using water contact angle, zeta-potential, Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and transmission electron microscopy (TEM) techniques. HNTs-g-CS exhibit a maximum 90.8% entrapment efficiency and 3.4% loading capacity of curcumin, which are higher than those of raw HNTs. HNTs-g-CS also show no obvious hemolytic phenomenon and good stability in serum. The cumulative release ratio of curcumin from HNTs-g-CS/curcumin at cell lysate after 48 hours is 84.2%. The curcumin loaded HNTs-g-CS show specific toxicity to various cancer cell lines, including HepG2, MCF-7, SV-HUC-1, EJ, Caski and HeLa, and demonstrate an inhibition concentration of IC50 at 5.3-192 μM as assessed by cytotoxicity studies. The anticancer activity of this nanoformulation is extremely high in EJ cells compared with the other cancer cell lines. The cell uptake of HNTs-g-CS is confirmed by fluorescence microscopy. Flow cytometric analysis of curcumin loaded HNTs-g-CS shows that curcumin loaded HNTs-g-CS increase apoptosis on EJ cells. The content of ROS created by HNTs-g-CS/curcumin is more than that of free curcumin. All these results suggest that HNTs-g-CS are potential nanovehicles for anticancer drug delivery in cancer therapy.

Designing Core–Shell Gold and Selenium Nanocomposites for Cancer Radiochemotherapy

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.

Differential Effects of Polymer-Surface Decoration on Drug Delivery, Cellular Retention, and Action Mechanisms of Functionalized Mesoporous Silica Nanoparticles

Polymer-surface decoration has been found to be an effective strategy to enhance the biological activities of nanomedicine. Herein, three different types of polymers with a cancer-targeting ligand Arg-Gly-Asp peptide (RGD) have been used to decorate mesoporous silica nanoparticles (MSNs) and the functionalized nanosystems were used as drug carriers of oxaliplatin (OXA). The results showed that polymer-surface decoration of the MSNs nanosystem by poly(ethylene glycol) (PEG) and polyethyleneimine (PEI) significantly enhanced the anticancer efficacy of OXA, which was much higher than that of chitosan (CTS). This effect was closely related to the enhancement of the cellular uptake and cellular drug retention. Moreover, PEI@MSNs-OXA possessed excellent advantages in penetrating ability and inhibitory effects on SW480 spheroids that were used to simulate the in vivo tumor environments. Therefore, this study provides useful information for the rational design of a cancer-targeted MSNs nanosystem with polymer-surface decoration.

A Cancer-Targeted Nanosystem for Delivery of Gold(III) Complexes: Enhanced Selectivity and Apoptosis-Inducing Efficacy of a Gold(III) Porphyrin Complex

Construction of delivery systems for anticancer gold complexes to decrease their toxicity while maintaining efficacy is a key strategy to optimize and develop anticancer gold medicines. Herein, we describe cancer-targeted mesoporous silica nanoparticles (MSN) for delivery of a gold(III) porphyrin complex (Au-1 a@MSN(R)) to enhance its anticancer efficacy and selectivity between cancer and normal cells. Encapsulation of Au-1 a within mesoporous silica nanoparticles amplifies its inhibitory effects on thioredoxin reductase (TrxR), resulting in a loss of redox balance and overproduction of reactive oxygen species (ROS). Elevated cellular oxidative stress activates diversified downstream ROS-mediated signaling pathways, leading to enhanced apoptosis-inducing efficacy.

The rational design of NAMI-A-loaded mesoporous silica nanoparticles as antiangiogenic nanosystems

Angiogenesis is essential for tumorous progression and metastasis. The RGD (Arg-Gly-Asp acid) peptide has been demonstrated to be a remarkable targeting reagent and can be distinguished by the integrin receptor overexpressed in various human tumor cells. Mesoporous silica nanoparticles (MSNs) are one of the most promising carriers applied for delivery of drugs or genes. It is well known that NAMI-A is an excellent drug for antimigration of tumor cells. Targeting the tumor vasculature with RGD-modified nanomaterials is expected to be a promising strategy for cancer therapy. Herein we have investigated the antiangiogenic activity of NAMI-A-loaded and RGD peptide surface decorated mesoporous silica nanoparticles in vitro and in vivo. The results revealed that NAMI-A@MSN-RGD remarkably enhanced the cellular uptake and antiangiogenic efficacy in contrast to bare NAMI-A in vitro. The nanosystem of NAMI-A@MSN-RGD also exhibited inspiring antiangiogenic action in vivo. Furthermore, the RGD-functionalized nanodrug inhibited angiogenesis by means of apoptosis by triggering ROS-mediated DNA damage in human umbilical vein endothelial cells (HUVECs). Our results suggested that the use of RGD-peptide modified MSNs as a vehicle of anticancer drugs is an efficient way to construct cancer-targeted nanosystems with antiangiogenic activity.

Tailored mesoporous silica nanosystem with enhanced permeability of the blood–brain barrier to antagonize glioblastoma

Cancer-targeted drug delivery systems with permeability of the blood-brain barrier (BBB) have become of great interest for the rational design of high-efficiency anticancer agents. Herein, a tailored mesoporous silica nanoparticles (MSNs) nanosystem modified by RGD (arginine-glycine-aspartate) peptide was designed and tested for use as a carrier of anticancer agents, by using a novel organic selenium compound BSeC as a model molecule. As expected, the nanosystem (BSeC@MSNs-RGD) could effectively enhance the BBB permeability and the cellular uptake of BSeC in tumor cells. The internalized BSeC@MSNs-RGD triggered mitochondrial dysfunction and intracellular ROS overproduction, which subsequently activated the p53 and MAPKs pathways. Moreover, the nanosystem could inhibit the U87 tumor spheroids growth, significantly prolong the blood circulation time of the loaded drug in vivo and effectively reduce its in vivo toxicity. Taken together, this study provides a strategy for the rational design of a tailored nanomedicine with enhanced BBB permeability to treat human brain glioma.

Controlled synthesis and size effects of multifunctional mesoporous silica nanosystem for precise cancer therapy

Abstract Nanomaterials-based drug delivery systems display potent applications in cancer therapy, owing to the enhanced permeability and retention effect and diversified chemical modification. In this study, we have tailored and synthesized different sized mesoporous silica nanoparticles (MSNs) through reactant control to investigate the relevancy of nanoparticle size toward anticancer efficacy and suppressing cancer multidrug resistance. The different sized MSNs loaded with anticancer ruthenium complex (RuPOP) and conjugated with folate acid (FA) to enhance the selectivity between cancer and normal cells. The nanosystem (Ru@MSNs) can specifically recognize HepG2 hepatocellular carcinoma cells, thus enhance accumulation and selective cellular uptake. The smaller sized (20 nm) Ru@MSNs exhibit higher anticancer activity against HepG2 cells, while the larger sized (80 nm) Ru@MSNs exhibit higher inhibitory effect against DOX-resistant hepatocellular carcinoma cells (R-HepG2). Moreover, Ru@MSNs induced ROS overproduction in cancer cells, leading to DNA damage and p53 phosphorylation, consequently promoting cancer cells apoptosis. Ru@MSNs (80 nm) also inhibited ABCB1 and ABCG2 expression in R-HepG2 cells to prevent drug efflux, thus overcome multidrug resistance. Ru@MSNs also inhibited tumor growth in vivo without obvious toxicity in major organs of tumor-bearing nude mice. Taken together, these results verify the size effects of MSNs nanosystem for precise cancer therapy.

Cancer-Targeting Functionalization of Selenium-Containing Ruthenium Conjugate with Tumor Microenvironment-Responsive Property to Enhance Theranostic Effects

A mutifunctional ruthenium-based conjugate Ru-BSe was designed and synthesized. The Ru complex with favorable bioimaging function was covalently linked with a cancer-targeted molecule that could be effectively internalized by the tumor to realize enhanced theranostic effects. The pH-response of the Ru conjugate in tumor acidic microenvironment causes ligand substitution and release of therapeutic complex. This activated complex remains inert to the reducing biomolecule-glutathione and terminally locates in mitochondria, in which it triggers oxidative stress, and activates intrinsic apoptosis. Real-time monitoring reveals that this Ru conjugate could selectively accumulate in tumor tissue in vivo, which significantly suppresses tumor progression and alleviate the damage to normal organs, realizing the precise cancer theranosis.

A highly selective dual-therapeutic nanosystem for simultaneous anticancer and antiangiogenesis therapy

The rational design of highly selective and cancer-targeted nanodrug delivery systems with attractive anticancer activities is urgently needed for future exploration and translational application of nanomedicine. As angiogenesis and tumor growth could be mutually enhanced, dual therapeutic nanomedicine with simultaneous antiangiogenesis and anticancer activities is practical for cancer therapy. Therefore, herein we have rationally designed functionalized mesoporous silica nanoparticles (MSNs) to realize the dual therapy of tumor growth and angiogenesis based on the biochemical similarity of membranes of cancer cells and angiogenic cells. This nanosystem demonstrates high selectivity in vivo against cancer cells with high integrin expression levels in two-tumor bearing models, and could simultaneously inhibit cancer cell growth and disrupt tumor neovasculature, thus achieving satisfactory in vivo anticancer efficacy. Interestingly, the nanosystem triggers ROS overproduction in both cancer and human umbilical vein endothelial cells, which activates various downstream signaling pathways to regulate cell cycle arrest and apoptosis. Moreover, the nanosystem also effectively reduces the toxic side effects of loaded drugs to normal tissues and prolongs blood circulation in vivo. Therefore, this study provides a simple approach for facile manufacture of a potent nanodrug delivery system that could achieve dual therapy of tumor growth and angiogenesis.

Tea regimen, a comprehensive assessment of antioxidant and antitumor activities of tea extract produced by Tie Guanyin hybridization

A comprehensive assessment was conducted in this study to examine the antioxidant and antitumor activities of tea extract produced by Tie Guanyin hybridization. Two radical-scavenging systems of assay in vitro, namely ABTS and DPPH assays, were used to investigate the antioxidant activity of the summer tea and autumn tea extract (STE and ATE) derived from the Jin Guanyin. The results indicated that the major active ingredients were catechins, and the theaflavin is rare in the STE and ATE. Moreover, STE and ATE could significantly suppress the growth of human breast cancer cells MDA-MB-231 in a dose-dependent manner, and wrecked the morphology of mitochondria, activated caspase families, leading to the cancer cell death by both apoptosis and cell cycle arrest pathways. Based on the results from an MDA-MB-231 xenograft nude mice model, STE could effectively prevent the tumor formation, and greatly improve the mice immunity and thus improve their living conditions. Taken together, ATE and STE could act as a healthy and prospective substitute for natural antioxidants and a promising prophylactic agent against cancer. This finding provides a great promising nutritional approach to treat diseases related with oxidative stress.