Hollow Mesoporous Silica Nanoparticles for Dual Chemo-starvation Therapy of Hepatocellular Carcinoma.

PURPOSE: This study aims at chemotherapy and starvation therapy of HCC via starvation and apoptosis. METHODS: Hollow mesoporous organosilica nanoparticles (HMONs) with the thioether-hybrid structure were developed using an organic/inorganic co-templating assembly approach. Hydrofluoric acid was used to remove the internal MSN core for yielding large radial mesopores for loading drug cargos. The morphology and structure of NPs were determined using TEM and SEM. HMONs were stepwise surface modified with glucose oxidase (GOx), oxygen (O2) and Doxorubicin (DOX), and cancer cell membrane (CCM) for yielding CCM-coated HMONs (targeted stealth biorobots; TSBRs) for starvation, apoptotic, and enhanced cell uptake properties, respectively. The surface area and pore size distribution were determined via BET and BJH assays. The catalytic ability of GOx-modified NPs was measured using in vitro glucose conversion approach authenticated by H2O2 and pH determination assays. MTT assay was used to determine the cytotoxicities of NPs. Cell uptake and apoptotic assay were used for the NPs internalization and apoptosis mechanisms. The subcutaneous HepG2 tumor model was established in mice. The long-term in vivo toxicity was determined using blood assays. RESULTS: The prepared NPs were spherical, hollow and mesoporous with excellent surface area and pore size distribution. The GOx-modified NPs exhibited excellent catalytic activity. The TSBRs showed better cytotoxicity and reduce the tumor size and weight. The NPs showed long-term safety in vivo. CONCLUSION: TSBRs destroyed cancer cells by starvation and chemotherapy in both in-vitro and in-vivo settings which demonstrates its anti-cancer potential.

Ultrasmall iron oxide nanoparticles cause significant toxicity by specifically inducing acute oxidative stress to multiple organs.

BACKGROUND: Iron oxide nanoparticles have been approved by food and drug administration for clinical application as magnetic resonance imaging (MRI) and are considered to be a biocompatible material. Large iron oxide nanoparticles are usually used as transversal (T2) contrast agents to exhibit dark contrast in MRI. In contrast, ultrasmall iron oxide nanoparticles (USPIONs) (several nanometers) showed remarkable advantage in longitudinal (T1)-weighted MRI due to the brighten effect. The study of the toxicity mainly focuses on particles with size of tens to hundreds of nanometers, while little is known about the toxicity of USPIONs. RESULTS: We fabricated Fe3O4 nanoparticles with diameters of 2.3, 4.2, and 9.3 nm and evaluated their toxicity in mice by intravenous injection. The results indicate that ultrasmall iron oxide nanoparticles with small size (2.3 and 4.2 nm) were highly toxic and were lethal at a dosage of 100 mg/kg. In contrast, no obvious toxicity was observed for iron oxide nanoparticles with size of 9.3 nm. The toxicity of small nanoparticles (2.3 and 4.2 nm) could be reduced when the total dose was split into 4 doses with each interval for 5 min. To study the toxicology, we synthesized different-sized SiO2 and gold nanoparticles. No significant toxicity was observed for ultrasmall SiO2 and gold nanoparticles in the mice. Hence, the toxicity of the ultrasmall Fe3O4 nanoparticles should be attributed to both the iron element and size. In the in vitro experiments, all the ultrasmall nanoparticles (< 5 nm) of Fe3O4, SiO2, and gold induced the generation of the reactive oxygen species (ROS) efficiently, while no obvious ROS was observed in larger nanoparticles groups. However, the ·OH was only detected in Fe3O4 group instead of SiO2 and gold groups. After intravenous injection, significantly elevated ·OH level was observed in heart, serum, and multiple organs. Among these organs, heart showed highest ·OH level due to the high distribution of ultrasmall Fe3O4 nanoparticles, leading to the acute cardiac failure and death. CONCLUSION: Ultrasmall Fe3O4 nanoparticles (2.3 and 4.2 nm) showed high toxicity in vivo due to the distinctive capability in inducing the generation of ·OH in multiple organs, especially in heart. The toxicity was related to both the iron element and size. These findings provide novel insight into the toxicology of ultrasmall Fe3O4 nanoparticles, and also highlight the need of comprehensive evaluation for their clinic application.

Design, synthesis and mechanistic studies of a TICT based fluorogenic probe for lighting up protein HSA.

Human serum albumin (HSA) in blood serves as an important biomarker for clinical diagnosis, and fluorescence sensing method has attracted extensive attention. In this work, a small organic molecule probe, YS8, involving twisted intramolecular charge transfer (TICT) characteristic, was designed and investigated to detect HSA. YS8 kept silent state in fluorescence under physiological conditions, but the encapsulation of YS8 in the hydrophobic subdomain IB region of HSA inhibited the TICT state and produced a clear light-up fluorescent signal. Especially, YS8 was demonstrated to be an efficient fluorogenic probe to discriminate HSA from other proteins including the bovine serum albumin (BSA). Moreover, YS8/HSA complex could be applied in fluorescence imaging in living cells and is also useful in the study of artificial fluorescent protein (AFP).

Optimization of activity localization of quinoline derivatives: Design, synthesis, and dual evaluation of biological activity for potential antitumor and antibacterial agents.

A novel of quarternary amine around a quinolinium iodide combined with even number alkyl chain were prepared in a several step in moderate yield starting from malonic ester and benzo[d][1,3]dioxol-5-amine. All of the active structure compounds were identified by nuclear magnetic resonance (NMR), such as 1H NMR, 13C NMR, infrared radiation (IR), high resolution mass spectrometry (HR-MS) and Carlo Erba Instruments CHNS-O EA1108 spectra analysis. With regard to the anticancer properties, the in vitro cytotoxicity against three human cancer cell lines (A-549, Hela and SGC-7901) were evaluated. The antibacterial properties against two human bacterial strains, Escherichia coli (ATCC 29213) and Staphylococcus aureus (ATCC 8739), along with minimum inhibitory concentration (MIC) values were evaluated. The target compounds, 5-12, exhibited significant antitumor and antibacterial activity, of which compound 12 was found to be the most potent derivative with IC50 values of 5.18 ± 0.64, 7.62 ± 1.05, 17.59 ± 0.41, and 54.45 ± 4.88 against A-549, Hela, SGC-7901, and L-02 cells, respectively, stronger than the positive control 5-FU and MTX. Furthermore, compound 12 had the most potent inhibitory activity. The MIC of this compound against Escherichia coli (ATCC 29213) and Staphylococcus aureus (ATCC 8739) was 3.125 nmol·mL-1, which was smaller than that of the reference agents, amoxicillin and ciprofloxacin.

Near-infrared light-responsive nanoparticles with thermosensitive yolk-shell structure for multimodal imaging and chemo-photothermal therapy of tumor.

Thermosensitive yolk-shell nanoparticles were developed as remote-controlled targeting drug delivery platform for multimodal imaging and combined therapy of cancer. The nanoparticles were fabricated using magnetic Fe3O4 nanoparticles as photothermal cores, thermo-responsive poly(N-isopropylacrylamide)-co-1-Vinyl-2-pyrrolidone p(NIPAM-co-NVP) as shells (Fe3O4-PNIPAM), with a hollow space between the two layers for loading of chemotherapeutic drug. The magnetic iron oxide nanoparticle cores could absorb and transform light to heat efficiently upon the irradiation of near infrared (NIR) laser, resulting in the shrink of the PNIPAM shell and the release of chemo-drugs. In vivo fluorescence/photoacoustic images demonstrated that Fe3O4-PNIPAM nanoparticles could accumulate in the tumor after intravenous injection. Upon the irradiation of the NIR laser, DOX-Fe3O4-PNIPAM nanoparticles exhibited outstanding synergistic effect. The tumor inhibition rate increased from 40.3% (DOX-Fe3O4-PNIPAM alone) and 65.2% (Fe3O4-PNIPAM +NIR) to 91.5%. The results demonstrated that the NIR-responsive nanocarrier offers a novel strategy for cancer theranostics and combined therapy of cancer.

[Application of magnetic iron oxide nanoparticles in magnetic resonance / photothermal dual-modal imaging].

In this study, water-dispersible magnetic iron oxide (Fe3O4) nanoparticles were synthesized with solvothermal method. The nanoparticles were characterized with a transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The in vitro magnetic resonance response and photothermal conversion characteristics of the nanoparticles were evaluated. In addition, the cellular uptake, cytotoxicity and biodistribution were studied. Finally, magnetic resonance/photothermal dual-modal imaging effect of the as-synthesized Fe3O4 nanoparticles was investigated in the tumor-bearing mice. The results showed that the obtained magnetic nanoparticles were uniform with a mean diameter of about 125 nm. Moreover, the superparamagnetic Fe3O4 nanoparticles showed remarkable magnetic resonance response and photothermal conversion properties. The results of cellular experiments showed that the cell viability was nearly 85% even the concentration of the nanoparticles was up to 1 000 µg·mL−1, an indicator of good biocompatibility. In addition, the nanoparticles could be taken up by the tumor cells and then located in the cytoplasm. After intravenous injection, the nanoparticles were tended to enrich in the tumor over time, which is helpful in achieving dual-modal magnetic resonance/photothermal imaging. In sum, the obtained Fe 3O4 nanoparticles showed great potential to be applied for multi-modal bio-imaging which may play an important role in the diagnosis of tumors.

Collagen/chitosan/genipin hydrogel loaded with phycocyanin nanoparticles and ND-336 for diabetic wound healing.

Diabetic wound healing remains a healthcare challenge due to the overexpression of matrix metalloproteinase-9 (MMP-9) and the imbalance between angiogenic factors and vascular inhibitory factors. In this study, we developed a nanocomposite injectable collagen/chitosan hydrogel for the treatment of delayed diabetic wound healing, which can promote cell migration to the wound site (through the addition of phycocyanin) and reduce the expression of MMP-9 (through the use of ND-336) to improve the therapeutic effect of diabetic wound healing. Furthermore, different weight ratios of collagen and chitosan hydrogels were prepared to select the hydrogel with proper mechanical properties. In vitro experiments confirmed that all hydrogels have favorable biocompatibility and hemocompatibility. Notably, Gel 2, with a weight ratio of collagen and chitosan at 25:75, was found to have an excellent capability to facilitate cell migration and in vivo studies further proved that Gel 2 nanocomposite hydrogel had the best ability to improve diabetic wound healing by promoting cell migration and decreasing MMP-9 expression. The collagen/chitosan/genipin hydrogel loaded phycocyanin and ND-336 can be harnessed for non-toxic and efficient treatment of wound healing management of diabetes.

Tween 80 Micelles Loaded with Fe3O4 Nanoparticles and Artemisinin for Combined Oxygen-Independent Ferroptosis Therapy of Cancer.

Artemisinin has an endoperoxide bridge structure, which can be cleaved by ferrous ions to generate various carbonyl radicals in an oxygen-independent manner, highlighting its potential for treating hypoxic tumors. In our study, we fabricated Tween 80 micelles loaded with Fe3O4 nanoparticles and artemisinin for cancer therapy. The synthesized Fe3O4 nanoparticles and drug-loaded micelles have particle sizes of about 5 nm and 80 nm, respectively, both exhibiting excellent dispersibility and stability. After uptake by MCF-7 cells, drug-loaded micelles release Fe2+ and ART into the cytoplasm, effectively inducing the generation of reactive oxygen species (ROS) in hypoxic conditions, thereby enhancing toxicity against cancer cells. In vitro and in vivo studies have demonstrated that ART and Fe3O4 nanoparticles are encapsulated in Tween 80 to form micelles, which effectively prevent premature release during circulation in the body. Although free ART and Fe3O4 nanoparticles can inhibit tumor growth, TW80-Fe3O4-ART micelles demonstrate a more pronounced inhibitory effect, with a tumor suppression rate of up to 85%. A novel strategy based on artemisinin and ferroptosis is thus offered, holding a favorable prospect for hypoxic cancer therapy.

Macrophages-mediated delivery of protoporphyrin for sonodynamic therapy of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by infiltration of inflammatory cells, hyperplasia of synovium, and destruction of the joint cartilage. Owing to the low drug delivery efficiency and limited immunosuppression effect, complete cure for RA remains a formidable challenge. Here, we show that live macrophages (Mφs) carrying protoporphyrin-loaded Fe3O4 nanoparticles can migrate to the RA tissues and inhibit the inflammation by sonodynamic therapy. The inflammation of RA leads to the release of cytokines, which guides the migration of the Mφs into the RA tissues, realizing precise delivery of therapeutics. The following sonodynamic therapy induced by ultrasound and protoporphyrin destructs the proliferating synovial cells and also infiltrated inflammatory cells, demonstrating significant therapeutic effect for RA. Meanwhile, the cytokines and relapse of RA can be remarkably suppressed because of the efficient damage to the resident inflammatory cells.

Extraction of trace tilmicosin in real water samples using ionic liquid-based aqueous two-phase systems.

The effective method of ionic liquid-based aqueous two-phase extraction, which involves ionic liquid (IL) (1-butyl-3-methyllimidazolium chloride, [C4mim]Cl) and inorganic salt (K2HPO4) coupled with high-performance liquid chromatography (HPLC), has been used to extract trace tilmicosin in real water samples which were passed through a 0.45 µm filter. The effects of the different types of salts, the concentration of K2HPO4 and of ILs, the pH value and temperature of the systems on the extraction efficiencies have all been investigated. Under the optimum conditions, the average extraction efficiency is up to 95.8%. This method was feasible when applied to the analysis of tilmicosin in real water samples within the range 0.5-40 µg mL(-1). The limit of detection was found to be 0.05 µg mL(-1). The recovery rate of tilmicosin was 92.0-99.0% from the real water samples by the proposed method. This process is suggested to have important applications for the extraction of tilmicosin.

[Preparation and in vitro evaluation of doxorubicin-loaded magnetic iron oxide nanoparticles].

PEG-modified magnetic Fe3O4 (Fe3O4-PEG) nanoparticles were sythesized using a solvothermal reaction and characterized with transmission electron microscopy (TEM) and thermo gravimetric analysis (TGA). The photothermal effect and photothermal destruction of cancer cells were evaluated. Then the doxorubicin loaded Fe3O4-PEG (DOX-Fe3O4-PEG) nanoparticles were prepared. The cytotoxicity and combined chemotherapy/photothermal therapy (PTT) effect were investigated. Uniform PEG coated Fe3O4 nanoparticles with particle size of 155 nm were obtained in the experiment. The loading and release of doxorubicin on Fe3O4-PEG were pH-dependent. The drug loading capacity in water was 21%. The results of MTT indicated a good biocompatiblity of Fe3O4-PEG nanoparticles and high cytotoxicity of DOX-Fe3O4-PEG. In combined therapy experiment, photothermal therapy demonstrated unambiguously enhanced chemotherapy efficacy. In conclusion, the obtained Fe3O4-PEG nanoparticles which exhibit good photothermal effect and drug loading capacity can be used for chemotherapy and photothermal therapy. The synergetic anti-tumor activity indicates the potential for the combined application of chemotherapy and photothermal therapy in cancer treatment.

One-Step Fabrication of Multifunctional PLGA-HMME-DTX@MnO2 Nanoparticles for Enhanced Chemo-Sonodynamic Antitumor Treatment.

Background: Sonodynamic therapy (SDT) and its synergistic cancer therapy derivatives, such as combined chemotherapy-SDT (chemo-SDT), are promising approaches for tumor treatment. However, the main drawbacks restricting their applications are hypoxia in tumors and the reducing microenvironment or high glutathione (GSH) levels. Methods: In this study, a hybrid metal MnO2 was deposited onto nanoparticles fabricated using poly(lactic-co-glycolic acid) (PLGA), carrying docetaxel (DTX) and the sonosensitizer hematoporphyrin monomethyl ether (HMME) (PHD@MnO2) via a one-step flash nanoprecipitation (FNP) method. Characterization and in vitro and in vivo experiments were conducted to explore the chemo-SDT effect of PHD@MnO2 and evaluate the synergetic antitumor treatment of this nanosystem. Results: When low-power ultrasound is applied, the acquired PHD@MnO2, whether in solution or in MCF-7 cells, generated ROS more efficiently than other groups without MnO2 or those treated via monotherapy. Specifically, GSH-depletion was observed when MnO2 was introduced into the system. PHD@MnO2 presented good biocompatibility and biosafety in vitro and in vivo. These results indicated that the PHD@MnO2 nanoparticles overcame hypoxia in tumor tissue and suppressed the expression of hypoxia-inducible factor 1 alpha (HIF-1α), achieving enhanced chemo-SDT. Conclusion: This study provides a paradigm that rationally engineered multifunctional metal-hybrid nanoparticles can serve as an effective platform for augmenting the antitumor therapeutic efficiency of chemo-SDT.

Appropriate Size of Fe3O4 Nanoparticles for Cancer Therapy by Ferroptosis.

Iron oxide nanoparticles can induce cell death due to the ferroptosis mechanism, showing a great potential for cancer therapy. Here, we synthesized different-sized iron oxide nanoparticles (2-100 nm) to investigate their antitumor effect and toxicity mechanism. It was found that ultrasmall nanoparticles (< ∼5 nm) could accumulate in nucleus and were more efficient in triggering the generation of •OH than larger nanoparticles due to the quicker release of Fe2+, thus exhibiting more remarkable cytotoxicity. Nevertheless, 10 nm iron oxide nanoparticles group displayed the best antitumor effect in vivo. We studied the in vivo and intratumoral biodistribution of the nanoparticles and found that the therapeutic effects were related to both the tumoral accumulation and intratumoral distribution of nanoparticles. This work indicates the appropriate size of Fe3O4 NPs for cancer treatment and illustrates the possible factors that influence the therapeutic effect, suggesting the great potential of iron oxide in clinical application.

Cell-Membrane-Coated Cationic Nanoparticles Disguised as Macrophages for the Prevention and Treatment of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by low-grade inflammation and insulin resistance. In this process, innate immune cells play a crucial role in recognizing the stimuli (free fatty acid, lipopolysaccharide, and cytokines) and mediating the inflammatory response, contributing to the development of T2DM. Neutralizing inflammatory cytokines and blocking the inflammation cascade provide great potential for the treatment of T2DM. Here, we applied a macrophage membrane as a bait, which could specifically recognize and bind the stimuli, to encapsulate nanoparticles and capture the stimuli, further preventing inflammation. The in vivo experiment results suggest that the nanoparticles could reduce the production of proinflammatory cytokines, decrease insulin resistance, and realize significant therapeutic effects for T2DM. A potential strategy is thus offered for blocking immune response, holding a wide application in metabolic and autoimmune diseases.

A new approach based on CXCR4-targeted combination liposomes for the treatment of liver fibrosis.

Liver fibrosis results from excessive extracellular matrix accumulation due to injury and leads to cirrhosis, cancer, and death. Herein, we propose a chemokine receptor 4 (CXCR4)-targeted combination (CTC) liposomal therapy to treat carbon tetrachloride (CCl4)-induced liver fibrosis in a mouse model. This study aims to combine small molecules such as pirfenidone and AMD3100 in a single nanoplatform to investigate their synergistic antifibrotic effects in a setting of CCl4-induced liver fibrosis. CTC liposomes (CTC lipo) were prepared using the thin-film hydration method. CTC lipo exhibited a spherical shape, and the particle size was recorded at the nanoscale which confirms its appropriateness for in vitro and in vivo applications. CTC lipo had good storage and serum stability. The entrapped drugs in CTC lipo showed reduced toxicity at higher concentrations. CTC lipo displayed CXCR4 mediated cell uptake and were internalized by caveolae-mediated endocytosis. CTC lipo showed CXCR4 targeting and stromal cell-derived factor 1α (SDF1-α)/CXCR4 axis blocking activity. CTC lipo reduced the elevated serum aspartate aminotransferase (AST), alanine transaminase (ALT), and hydroxyproline (HYP) levels. The histological studies showed improved liver architecture and reduced collagen deposition after treatment. Transforming growth factor ß (TGFß), alpha-smooth muscle actin (α-SMA), and collagen I were elevated by CCl4 in comparison with the Sham. Upon CTC liposomal treatment, the quantitative score for the elevated fibrotic proteins such as TGFß, α-SMA, and collagen I was normalized. CTC lipo displayed significant downregulation of the upregulated TGFß, α-SMA, collagen I, and P-p38 expressions at the molecular level. The CXCR4 targeted liposomes showed prolonged biodistribution at 24 h. Our findings indicated that CTC lipo might be an alternative antifibrotic therapy that may offer new access to research and development. In a nutshell, the present study suggests that systemic administration of CTC lipo has efficient antifibrotic potential and deserves to be investigated for further clinical applications.

Phycocyanin Nanoparticle as a Novel Sonosensitizer for Tumor Sonodynamic Therapy of Michigan Cancer Foundation-7 Cells In Vitro.

The development of novel sonosensitizers with safety and efficiency is a key problem in anti-tumor sonodynamic therapy. Phycocyanin (PC) has been proved to have the singlet oxygen radicals (ROS) generation ability, and the potential of PC as a novel sonosensitizer has been investigated. To overcome the disadvantages of PC in vivo, such as poor stability and low half-life, PC nanoparticles (PCNP) were prepared by the cross-linking method. According to the results, PCNP has been found with good morphology, good particle size distribution and good stability. Human breast cancer cell line MCF-7 was used to investigate PCNP cell uptake ability. ROS generation and cytotoxicity under ultrasonic irradiation (sonotoxicity) were also studied on this cell. Under the condition of 0.75 w/cm² ultrasound, PCNP has a good ROS productivity and is equivalent to the sonotoxicity of the known sonosensitizer hematoporphyrin monomethyl Ether (HMME). In conclusion, PCNP is expected to be developed as an effective sonosensitizer for the sonodynamic therapy of tumors.

Ultrasound responsive self-assembled micelles loaded with hypocrellin for cancer sonodynamic therapy.

Nanoparticles have been demonstrated to be effective in targeted drug delivery to tumor due to the enhanced permeability and retention (EPR) effect. However, the inhomogeneous distribution of the nanoparticles in the tumor and the slow release of the drug make the therapeutic effect unsatisfied. Here, we present reactive oxygen species (ROS)-responsive micelles comprising poly (ethylene glycol)-poly(propylene sulfide) (PEG-PPS) for targeted delivery and in situ release of drug. Upon the irradiation of ultrasound, the loaded sonosensitizer hypocrellin (HC) will generate ROS to trigger the disassembly of the micelles and meanwhile realize sonodynamic therapy (SDT) effect of cancer. The in vivo experiment indicates that the HC loaded PEG-PPS are biocompatible and much more efficacious than an equivalent amount of free HC in inhibiting the growth of cancer.

Concise Nanoplatform of Phycocyanin Nanoparticle Loaded with Docetaxel for Synergetic Chemo-sonodynamic Antitumor Therapy.

Combined chemotherapy and sonodynamic therapy (chemo-SDT) based on the nanoplatform/nanocarrier is a potential antitumor strategy that has shown higher therapeutic efficacy than any monotherapy. Therefore, a safe and effective multifunctional system with a concise design and simple preparation process is urgently needed. In this work, by using a one-step cross-linking method, a multifunctional nanosystem, which employs phycocyanin nanoparticles (PCNPs) as a nanocarrier to deliver the chemotherapy drug docetaxel (DTX) and a nanosonosensitizer to generate reactive oxygen species (ROS), was prepared and evaluated (PCNP-DTX). Under low-intensity ultrasound irradiation, PCNP-DTX retained the ROS generation ability of phycocyanin and caused the destruction of mitochondrial potential. PCNP was also revealed to be an acidic and ultrasound-sensitive carrier with good biocompatibility. In addition to its cumulation behavior in tumors, PCNP can achieve tumor-targeted delivery and release of DTX. PCNP-DTX has also been proven to have a significant chemo-SDT synergy effect when low-intensity ultrasound was applied, showing enhanced antitumor activity both in vitro and in vivo. This study provides a concise yet promising nanoplatform based on the natural protein phycocyanin for achieving an effective, targeted, and synergetic chemo-SDT for antitumor therapy.

CaO2/Fe3O4 nanocomposites for oxygen-independent generation of radicals and cancer therapy.

The hypoxic tumor environment prevents the generation of reactive oxygen species (ROS), reducing the therapeutic efficiency. We construct oleylamine (OA) coated CaO2/Fe3O4 nanocomposites to realize oxygen-independent generation of ROS and high efficient treatment of cancer. In the tumor site, CaO2 reacts with water to generate H2O2, which can be catalized by Fe2+ that is produced by Fe3O4, to form highly toxic hydroxyl radicals (∙OH). To inhibit the premature reaction, CaO2/Fe3O4 nanoparticles were coated with pH sensitive OA. The nanocomposites exhibited remarkable tumor growth inhibition ability and favorable biocompatibility, holding a great potential for hypoxic tumor therapy.

Cancer stem cells and strategies for targeted drug delivery.

Cancer stem cells (CSCs) are a small proportion of cancer cells with high tumorigenic activity, self-renewal ability, and multilineage differentiation potential. Standard anti-tumor therapies including conventional chemotherapy, radiation therapy, and molecularly targeted therapies are not effective against CSCs, and often lead to enrichment of CSCs that can result in tumor relapse. Therefore, it is hypothesized that targeting CSCs is key to increasing the efficacy of cancer therapies. In this review, CSC properties including CSC markers, their role in tumor growth, invasiveness, metastasis, and drug resistance, as well as CSC microenvironment are discussed. Further, CSC-targeted strategies including the use of targeted drug delivery systems are examined.