Glutathione-responsive core cross-linked micelles for controlled cabazitaxel delivery

Stimulus-responsive polymeric micelles (PMs) have recently received attention due to the controlled delivery of drug or gene for application in cancer diagnosis and treatment. In this work, novel glutathione-responsive PMs were prepared to encapsulate hydrophobic antineoplastic drug, cabazitaxel (CTX), to improve its solubility and toxicity. These CTX-loaded micelles core cross-linked by disulfide bonds (DCL-CTX micelles) were prepared by a novel copolymer, lipoic acid grafted mPEG-PLA. These micelles had regular spherical shape, homogeneous diameter of 18.97?±?0.23 nm, and a narrow size distribution. The DCL-CTX micelles showed high encapsulation efficiency of 98.65?±?1.77%, and the aqueous solubility of CTX was improved by a factor of 1:1200. In vitro release investigation showed that DCL-CTX micelles were stable in the medium without glutathione (GSH), whereas the micelles had burst CTX release in the medium with 10 mM GSH. Cell uptake results implied that DCL-CTX micelles were internalized into MCF-7 cells through clathrin-mediated endocytosis and released cargo more effectively than Jevtana (commercially available CTX) owing to GSH-stimulated degradation. In MTT assay against MCF-7 cells, these micelles inhibited tumor cell proliferation more effectively than Jevtana due to their GSH-responsive CTX release. All results revealed the potency of GSH-responsive DCL-CTX micelles for stable delivery in blood circulation and for intracellular GSH-trigged release of CTX. Therefore, DCL-CTX micelles show potential as safe and effective CTX delivery carriers and as a cancer chemotherapy formulation.     

Magnetic lipid nanoparticles loading doxorubicin for intracellular delivery: Preparation and characteristics

Tumor intracellular delivery is an effective route for targeting chemotherapy to enhance the curative effect and minimize the side effect of a drug. In this study, the magnetic lipid nanoparticles with an uptake ability by tumor cells were prepared dispersing ferroso-ferric oxide nanoparticles in aqueous phase using oleic acid (OA) as a dispersant, and following the solvent dispersion of lipid organic solution. The obtained nanoparticles with 200 nm volume average diameter and −30 mV surface zeta potential could be completely removed by external magnetic field from aqueous solution. Using doxorubicin (DOX) as a model drug, the drug-loaded magnetic lipid nanoparticles were investigated in detail, such as the effects of OA, drug and lipid content on volume average diameter, zeta potential, drug encapsulation efficiency, drug loading, and in vitro drug release. The drug loading capacity and encapsulation efficiency were enhanced with increasing drug or lipid content, reduced with increasing OA content. The in vitro drug release could be controlled by changing drug or lipid content. Cellular uptake by MCF-7 cells experiment presented the excellent internalization ability of the prepared magnetic lipid nanoparticles. These results evidenced that the present magnetic lipid nanoparticles have potential for targeting therapy of antitumor drugs.     

Effect of local dual frequency sonication on drug distribution from polymeric nanomicelles

To overcome the side effects caused by systemic administration of doxorubicin, nanosized polymeric micelles were used in combination with dual frequency ultrasonic irradiation. These micelles release the drug due to acoustic cavitation, which is enhanced in dual frequency ultrasonic fields. To form the drug-loaded micelles, Pluronic P-105 copolymer was used, and doxorubicin was physically loaded into stabilized micelles with an average size of 14 nm. In this study, adult female Balb/C mice were transplanted with spontaneous breast adenocarcinoma tumors and were injected with a dose of 1.3 mg/kg doxorubicin in one of three forms: free doxorubicin, micellar doxorubicin without sonication and micellar doxorubicin with sonication. To increase cavitation yield, the tumor region was sonicated for 2.5 min at simultaneous frequencies of 3 MHz (I(SATA)=2 W/cm(2)) and 28 kHz (I(SATA)=0.04 W/cm(2)). The animals were sacrificed 24h after injection, and their tumor, heart, spleen, liver, kidneys and plasma were separated and homogenized. The drug content in the tissues was determined using tissue fluorimetry (350 nm excitation and 560 nm emission), and standard drug dose curves were obtained for each tissue. The results show that in the group that received micellar doxorubicin with sonication, the drug concentration in the tumor tissue was significantly higher than in the free doxorubicin injection group (8.69 times) and the micellar doxorubicin without sonication group (2.60 times). The drug concentration in other tissues was significantly lower in the micellar doxorubicin with sonication group relative to the free doxorubicin (3.35 times) and the micellar drug without sonication (2.48 times) groups (p<0.05). We conclude that dual frequency sonication improves drug release from micelles and increases the drug uptake by tumors due to sonoporation. The proposed drug delivery system creates an improved treatment capability while reducing systemic side effects caused by drug uptake in other tissues.     

Intracellular Breakable and Ultrasound‐Responsive Hybrid Microsized Containers for Selective Drug Release into Cancerous Cells

This work reports an efficient and straightforward strategy to fabricate hybrid microsized containers with reduction‐sensitive and ultrasound‐responsive properties. The ultrasound and reductive sensitivity are visualized using scanning electron microscopy, with the results showing structural decomposition upon ultrasound irradiation and in the presence of reducing agent. The ultrasound‐responsive functionalities of hybrid carriers can be used as external trigger for rapid controlled release, while prolonged drug release can be achieved in the presence of reducing agent. To evaluate the potential for targeted drug delivery, hybrid microsized containers are loaded with the anticancer drug doxorubicin (Dox). Such hybrid capsules can undergo structural intracellular degradation after cellular uptake by human cervical cancer cell line (HeLa), resulting in Dox release into cancer cells. In contrast, there is no Dox release when hybrid capsules are incubated with human mesenchymal stem cells (MSCs) as an example of normal human cells. The cell viability results indicate that Dox‐loaded capsules effectively killed HeLa cells, while they have lower cytotoxicity against MSCs as an example of healthy cells. Thus, the newly developed intracellular‐ and ultrasound‐responsive microcarriers obtained via sol‐gel method and layer‐by‐layer technique provide a high therapeutic efficacy for cancer, while minimizing adverse side effect.     

Drug-loaded nano/microbubbles for combining ultrasonography and targeted chemotherapy

A new class of multifunctional nanoparticles that combine properties of polymeric drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasound-mediated drug delivery has been developed. At room temperature, the developed systems comprise perfluorocarbon nanodroplets stabilized by the walls made of biodegradable block copolymers. Upon heating to physiological temperatures, the nanodroplets convert into nano/microbubbles. The phase state of the systems and bubble size may be controlled by the copolymer/perfluorocarbon volume ratio. Upon intravenous injections, a long-lasting, strong and selective ultrasound contrast is observed in the tumor volume indicating nanobubble extravasation through the defective tumor microvasculature, suggesting their coalescence into larger, highly echogenic microbubbles in the tumor tissue. Under the action of tumor-directed ultrasound, microbubbles cavitate and collapse resulting in a release of the encapsulated drug and dramatically enhanced intracellular drug uptake by the tumor cells. This effect is tumor-selective; no accumulation of echogenic microbubbles is observed in other organs. Effective chemotherapy of the MDA MB231 breast cancer tumors has been achieved using this technique.     

Design and evaluation of dual CD44 receptor and folate receptor-targeting double-smart pH-response multifunctional nanocarrier

In this article, in order to enhance the bioavailiability and tumor targeting of curcumin (Cur), the oligosaccharides of hyaluronan conjugates, folic acid-oligosaccharides of hyaluronan-acetal-menthone 1,2-glycerol ketal (FA-oHA-Ace-MGK) carried oHA as a ligand to CD44 receptor, double-pH-sensitive Ace-MGK as hydrophobic moieties, and FA as the target of folate receptor. The structure characteristics of this smart response multifunctional dual-targeting nano-sized carrier was measured by fourier-transform infrared (FT-IR) and nuclear magnetic resonance (¹H–NMR). Cur, an anticancer drug, was successfully loaded in FA-oHA-Ace-MGK micelles by self-assembly. The measurement results of transmission electron microscopy (TEM) presented that the Cur-loaded micelles were spherical in shape with the average size of 166.3?±?2.12 nm and zeta potential ??30.07 mV. Much more encapsulated Cur could be released at mildly acidic environments than at pH 7.4, from the Cur-FA-oHA-Ace-MGK micelles. Cytotoxicity assay indicated that non-Cur loaded micelles mostly had no cytotoxicity to MCF-7 cells and A549 cells, and Cur-loaded micelles had significantly lower survival rate than Cur suspension in the same concentration, which proved that the drug-loaded micelles can effectively inhibit tumor cell growth. The targeting of CD44 receptors and folate receptors was proved in vitro cellular uptake assay. These results showed the promising potential of FA-oHA-Ace-MGK as an effective nano-sized carrier for anti-tumor drug delivery.     

Ultrasound responsive carbon monoxide releasing micelle

Carbon monoxide (CO), an endogenously produced gasotransmitter, has shown various therapeutic effects in previous studies. In this work, we developed an ultrasound responsive micelle for localized CO delivery. The micelle is composed of a pluronic shell and a core of a CO releasing molecule, CORM-2. The mechanism is based on the ultrasound response of pluronics, and the reaction between CORM-2 and certain biomolecules, e.g. cysteine. The latter allows CO release without significantly breaking the micelles. In a 3.5 mM cysteine solution, the micelles released low level of CO, indicating effective encapsulation of CORM-2. Treatment with a low intensity, non-focused ultrasound led to four times as much CO as the sample without ultrasonication, which is close to that of unencapsulated CORM-2. Significantly reduced proliferation of prostate cancer cells (PC-3) was observed 24 h after the PC-3 cells were treated with the CORM-2 micelles followed by ultrasound activation.     

Drug‐Conjugation Induced Self‐Assembly of Feather Keratin‐Based Prodrug for Tumor Intracellular Reduction Triggered Drug Delivery

As a kind of natural protein, keratin is widely investigated in the biomedical field. Here, for the first time, a keratin‐based prodrug (PK‐SS‐D) is designed for tumor intracellular reduction triggered drug delivery, by conjugating doxorubicin (DOX) onto poly(ethylene glycol) modified keratin (PEGylated keratin, PK) with a bioreducible disulfide linkage. The protein‐drug conjugate prodrug, with a drug content of 20%, can self‐assemble into micelles with a mean hydrodynamic diameter of 175 nm and a narrow distribution. The in vitro controlled release profiles reveal the reduction triggered thiolated DOX (DOX‐SH) release behavior of the PK‐SS‐D micelles, with a cumulative drug release up to 52% within 10 d in the simulated tumor microenvironment in a sustained releasing mode, and a low drug leakage of 17% in the simulated normal physiological medium. The enhanced tumor growth inhibition of the proposed PK‐SS‐D prodrug micelles is revealed by the methyl tetrazolium (MTT) assays, although the released DOX‐SH prodrug possesses a lower tumor growth inhibition than DOX.     

Ultrasound responsive block copolymer micelle of poly(ethylene glycol)–poly(propylene glycol) obtained through click reaction

The well-defined amphiphilic poly(ethylene glycol)-block-poly(propylene glycol) copolymer containing 1, 2, 3-triazole moiety and multiple ester bonds (PEG-click-PPG) was prepared by click reaction strategy. The PEG-click-PPG copolymer can self-assemble into spherical micelles in aqueous solution. It is found that high intensity focused ultrasound (HIFU) can open the copolymer PEG-click-PPG micelles and trigger the release of the payload in the micelle. The multiple ester bonds introduced in the junction point of the copolymer chain through click reactions were cleaved under HIFU, and leads to the disruption of the copolymer micelle and fast release of loaded cargo. The click reaction provides a convenient way to construct ultrasound responsive copolymer micelles with weak bonds.     

GLUT1-Targeting and GSH-Responsive DOX/L61 Nanodrug Particles for Enhancing MDR Breast Cancer Therapy

Efficient targeting to tumor tissues and subsequent rapid drug release in cancer cells remains a major challenge for nanodrug delivery systems. Herein, smart nanodrug particles with reduction-sensitive and active tumor-targeting ability are constructed based on the nanoprecipitation of glucosamine-grafted pluronic L61 (GA-L61) and disulphide-linked doxorubicin dimer (DOX SS DOX) to overcome tumor multidrug resistance (MDR). These nanoparticles show proper size and excellent stability under neutral conditions, while quickly release DOX due to the breakage of disulfide bonds under reductive medium. In vitro cellular uptake and drug efflux demonstrate that L61 can efficiently increase DOX concentration in MCF/ADR resistant cells by inhibiting the function of drug resistance proteins. In vivo biodistribution reveals that glucose transporter 1 (GLUT1)-mediated tumor-targeting significantly improves tumor accumulation of the glucosamine-contained nanoparticles. Finally, the combination of GLUT1-targeting, glutathione (GSH)-responsive, and MDR-reversal effects in nanoparticles achieve superior antitumor effects, which can provide an efficient, safe, and economic approach for drug delivery and cancer chemotherapy.     

Preparation and in vitro evaluation of an ultrasound-triggered drug delivery system: 10-hydroxycamptothecin loaded PLA microbubbles

10-Hydroxycamptothecin (HCPT) loaded PLA microbubbles, used as an ultrasound-triggered drug delivery system, were fabricated by a double emulsion-solvent evaporation method. The obtained microbubbles were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and confocal laser scanning microscope (CLSM). In addition, the effect of diagnostic ultrasound exposure on BEL-7402 cells combined with HCPT-loaded PLA microbubbles was evaluated using cytotoxicity assay, CLSM and flow cytometry (FCM). It was found that the HCPT-loaded PLA microbubbles showed smooth surface and spherical shape, and the drug was amorphously dispersed within the shell and the drug loading content reached up to 1.69%. Nearly 20% of HCPT was released upon exposure to diagnostic ultrasound at frequency of 3.5 MHz for 10 min. Moreover, HCPT fluorescence in the cells treated only with the HCPT-loaded PLA microbubbles was discernible, but less intense, while those treated with the microbubbles in conjunction with ultrasound exposure was evident and intense, indicating an increased cellular uptake of HCPT by ultrasound exposure. Cytotoxicity test on BEL-7402 cells indicated that the HCPT-loaded PLA microbubbles combined with ultrasound exposure were more cytotoxic than the microbubbles alone. The results suggest that the combination of drug loaded PLA microbubbles and diagnostic ultrasound exposure exhibit an effective intracellular drug uptake by tumor cells, indicating their great potential for antitumor therapy.     

Cellular uptake and radiosensitization of SR-2508 loaded PLGA nanoparticles

SR-2508 (etanidazole), a hypoxic radiosensitizer, has potential applications in radiotherapy. The poly(d,l-lactide-co-glycolide)(PLGA) nanoparticles containing SR-2508 were prepared by w/o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e. encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The cellular uptake of the nanoparticles for the two human tumor cell lines: human breast carcinoma cells (MCF-7) and human carcinoma cervices cells (HeLa), was evaluated by fluorescence microscopy and transmission electronic microscopy. Cell viability was measured by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 90 nm and 190 nm. The encapsulation efficiency was 20.06%. The drug release pattern exhibited an initial burst followed by a plateau for over 24 h. The cellular uptake of nanoparticles was observed. Co-culture of MCF-7 and HeLa cells with SR-2508 loaded nanoparticles showed that released SR-2508 retained its bioactivity and effectively sensitized two hypoxic tumor cell lines to radiation. The radiosensitization of SR-2508 loaded nanoparticles was more significant than that of free drug.     

两亲性壳聚糖基聚合物碳点的合成及其在载药方面的应用

通过水热法合成了系列具有高荧光量子产率（42.9%）辛基化壳聚糖基两亲性聚合物碳点荧光材料。利用红外光谱、紫外吸收光谱、光电子能谱、透射电镜、X射线衍射及荧光光谱对聚合物碳点进行了表征。以阿霉素为模型药物,研究了聚合物碳点对阿霉素的载药性能。当辛基取代度为76.42%时,其最大载药量和包封率分别为49.6%与47.4%。在磷酸盐缓冲液中,载药纳米胶束呈前期快速释放,后期缓慢释放的双相特征。将载药纳米胶束与鼻咽癌细胞作用,发现其存活率随着载药纳米胶束加入量的增加而降低,说明该纳米胶束对鼻咽癌细胞有一定的抑制作用。总之,该聚合物碳点材料在药物载体与荧光示踪方面有潜在的应用价值。     

High intensity focused ultrasound responsive release behavior of metallo-supramolecular block PPG-PEG copolymer micelles

An amphiphilic metallo-supramolecular poly(propylene glycol)-block-poly(ethylene glycol) block copolymer containing a bis(2,2′:6′,2″-terpyridine) ruthenium (II) complex as a supramolecular connection between the two constituting blocks was used to prepare stable aqueous micelles which displayed a high intensity focused ultrasound (HIFU) triggered release behavior. By adjusting the HIFU time and intensity, the novel modality of HIFU triggered release allows for fine-tuning of the release kinetics of the encapsulants from the micelles in a remote and controlled way. Nuclear magnetic resonance spectroscopy, ultraviolet spectroscopy, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry confirmed that the degradation of the micelles was due to the cleavage of the ether bond connected to the pyridine ring. This well controlled HIFU-copolymer micelle drug delivery system has considerable potential in targeted therapy.     

Small angle neutron scattering study of doxorubicin-surfactant complexes encapsulated in block copolymer micelles

Self-assembling behaviour of block copolymers and their ability to evade the immune system through polyethylene oxide stealth makes it an attractive candidate for drug encapsulation. Micelles formed by polyethylene oxide-polypropylene oxide- polyethylene oxide triblock copolymers (PEO-PPO-PEO), pluronic P123, have been employed for encapsulating the anti-cancer drug doxorubicin hydrochloride. The binding affinity of doxorubicin within the micelle carrier is enhanced through complex formation of drug and anionic surfactant, aerosol OT (AOT). Electrostatic binding of doxorubicin with negatively charged surfactants leads to the formation of hydrophobic drug-surfactant complexes. Surfactant-induced partitioning of the anti-cancer drug into nonpolar solvents such as chloroform is investigated. SANS measurements were performed on pluronic P123 micelles in the presence of drug-surfactant complex. No significant changes in the structure of the micelles are observed upon drug encapsulation. This demonstrates that surfactant- drug complexes can be encapsulated in block copolymer micelles without disrupting the structure of aggregates.      

Porous FeVO4 nanorods: synthesis,characterization, and gas-sensing properties toward volatile organic compounds

Herein, we describe a multifunctional anti-cancer prodrug system based on water-dispersible carbon nanotube (CNT); this prodrug system features active targeting, pH-triggered drug release, and photodynamic therapeutic properties. For this prodrug system (with the size of ~100–300 nm), an anti-cancer drug, doxorubicin (DOX), was incorporated onto CNT via a cleavable hydrazone bond; and a targeting ligand (folic acid) was also coupled onto CNT. This prodrug can preferably enter folate receptor (FR)-positive cancer cells and undergo intracellular release of the drug triggered by the reduced pH. The targeted CNT-based prodrug system can cause lower cell viability toward FR-positive cells compared to the non-targeted ones. Moreover, the CNT carrier exhibits photodynamic therapeutic (PDT) action; and the cell viability of FR-positive cancer cells can be further reduced upon light irradiation. The dual effects of pH-triggered drug release and PDT increase the therapeutic efficacy of the DOX–CNT prodrug. This study may offer some useful insights on designing and improving the applicability of CNT for other drug delivery systems.

     

Sonodynamic therapy

Recently, there have been numerous reports on the application of non-thermal ultrasound energy for treating various diseases in combination with drugs. Furthermore, the introduction of microbubbles and nanobubbles as carriers/enhancers of drugs has added a whole new dimension to therapeutic ultrasound. Non-thermal mechanisms for effects seen include various forms of energy due to cavitation, acoustic streaming, micro jets and radiation force which increases possibilities for targeting tissue with drugs, enhancing drug effectiveness or even chemically activating certain materials. Examples such as enhancement of thrombolytic agents by ultrasound have proven to be beneficial for acute stroke patients and peripheral arterial occlusions. Non-invasive low intensity focused ultrasound in conjunction with anti-cancer drugs may help to reduce tumor size and lessen recurrence while reducing severe drug side effects. Chemical activation of drugs by ultrasound energy for treatment of atherosclerosis and tumors is another new field recently termed as “Sonodynamic therapy”. Lastly, advances in molecular imaging have aroused great expectations in applying ultrasound for both diagnosis and therapy simultaneously. Microbubbles or nanobubbles targeted at the molecular level will allow medical doctors to make a final diagnosis of a disease using ultrasound imaging and then immediately proceed to a therapeutic ultrasound treatment.     

Acoustically active perfluorocarbon nanoemulsions as drug delivery carriers for camptothecin: drug release and cytotoxicity against cancer cells

Camptothecin is a topoisomerase I inhibitor that acts against a broad spectrum of cancers. However, its clinical application is limited by its insolubility, instability, and toxicity. The aim of the present study was to develop acoustically active nanoemulsions for camptothecin encapsulation to circumvent these delivery problems. The nanoemulsions were prepared using liquid perfluorocarbons and coconut oil as the cores of the inner phase. These nanoemulsions were stabilized by phospholipids and/or Pluronic F68 (PF68). The nanoemulsions were prepared at high drug loading of ∼100% with a mean droplet diameter of 220-420 nm. Camptothecin in these systems showed retarded drug release. Camptothecin in nanoemulsions with a lower oil concentration exhibited cytotoxicity against melanomas and ovarian cancer cells. Confocal laser scanning microscopy confirmed nanoemulsion uptake into cells. Hemolysis caused by the interaction between erythrocytes and the nanoemulsions was investigated. Formulations with phosphatidylethanolamine as the emulsifier showed less hemolysis than those with phosphatidylcholine. Using a 1 MHz ultrasound, an increased release of camptothecin from the system with lower oil concentration could be established, illustrating a drug-targeting effect.     

Carbon Dots‐Cluster‐DOX Nanocomposites Fabricated by a Co‐Self‐Assembly Strategy for Tumor‐Targeted Bioimaging and Therapy

Carbon‐based nanomaterials could afford versatile potential applications in biomedical optical imaging and as nanoparticle drug carriers, owing to their promising optical and biocompatible capabilities. In this paper, it is first found that amphipathic cetylpyridinium chloride (CPC)‐stabilized oil‐soluble carbon dots (CDs) could self‐assemble into hydrophilic CDs clusters with hydrophobic core under ultrasound, in which CPC acts as carbon source, stabilizer, and phase transfer agent. Next, the size‐control (for size‐dependent passive tumor targeting) and doxorubicin (DOX) uploading of aqueous CDs clusters, and subsequent surface charge modification via overcoating with cRGD‐ and octylamine‐modified polyacrylic acid (cRGD‐PAA‐OA) (reversing their surface charges into negative and introducing active tumor‐targeting ability) are explored systematically. Based on this sequential administration mode, CDs‐cluster‐DOX/cRGD‐PAA‐OA nanocomposites exhibit selective human malignant glioma cell line (U87MG) tumor targeting. In in vitro drug release experiments, the nanocomposites could release DOX timely. Owning to the dual tumor targeting effects and seasonable drug release, CDs‐cluster‐DOX/cRGD‐PAA‐OA show remarkably tumor targetability and enhanced antitumor efficacy (and reduced adverse reaction), comparing to free DOX in animal models. These results indicate that fabricating nanocomposite via co‐self‐assembly strategy is efficient toward drug delivery system for tumor‐targeting theranostic.     

Silver–titanium dioxide nanocomposites as effective antimicrobial and antibiofilm agents

Recent studies have revealed the existence of liver cancer stem cells (CSCs). Therefore, there is an urgent need for new and effective treatment strategies specific to liver CSCs. In this work, the poly(d,l-lactide-coglycolide) nanoparticles containing paclitaxel were prepared by emulsification-solvent evaporation method. The nanoparticles decorated with anti-CD133 antibody, termed targeted nanoparticles, were prepared by carbodiimide chemistry for liver CSCs. The physicochemical characteristics of the nanoparticles (i.e., encapsulation efficiency, particle size distribution, morphology, and in vitro release) were investigated. Cellular uptake and accumulation in tumor tissue of nanoparticles were observed. To assess anti-tumor activity of nanoparticles in vitro and in vivo, cell survival assay and tumor regression study were carried out using liver cancer cell lines (Huh7 and HepG2) and their xenografts. Particle size of targeted nanoparticles was 429.26 ± 41.53 nm with zeta potential of ?11.2 mV. Targeted nanoparticles possessed spherical morphology and high encapsulation efficiency (87.53 ± 5.9 %). The accumulation of targeted nanoparticles depends on dual effects of passive and active targeting. Drug-loaded nanoparticles showed cytotoxicity on the tumor cells in vitro and in vivo. Targeted nanoparticles resulted in significant improvement in therapeutic response through selectively eliminating CD133 positive subpopulation. These results suggested that the novel nanoparticles could be a promising candidate with excellent therapeutic efficacy for targeting liver CSCs.