Responsive Drug Delivery System Research Articles

Mechanism Investigation of Hyaluronidase-Combined Multistage Nanoparticles for Solid Tumor Penetration and Antitumor Effect.

BackgroundHyaluronic acid (HA) is a major component of extracellular matrix (ECM) and its over expression in tumor tissues contributes to the increase of interstitial fluid pressure (IFP) and hinders the penetration of nanoparticles into solid tumors.Materials and MethodsWe here reported a tumoral microenvironment responsive multistage drug delivery system (NPs-EPI/HAase) which was formed layer by layer via electrostatic interaction with epirubicin (EPI)-loaded PEG-b-poly(2-(diisopropylamino)ethyl methacrylate)-b-poly(2-guanidinoethylmethacrylate) (mPEG-PDPA-PG, PEDG) micelles (NPs-EPI) and hyaluronidase (HAase). In this paper, we focused on the hyaluronidase-combined nanoparticles (NPs-EPI/HAase) for tumor penetration in tumor spheroid and solid tumor models in vitro and in vivo.ResultsOur results showed that NPs-EPI/HAase effectively degrade the HA in ECM and facilitate deep penetration of NPs-EPI into solid tumor. Moreover, NPs-EPI mainly employed clathrin-mediated and macropinocytosis-mediated endocytic pathways for cellular uptake and were subsequently directed to the lysosomes for further drug release triggered by proton sponge effect. Compared with NPs-EPI, the HAase coating group showed an enhanced tumoral drug delivery efficacy and inhibition of tumor growth.ConclusionOverall, our studies demonstrated that coating nanoparticles with HAase can provide a simple but efficient strategy for nano-drug carriers to enhance solid tumor penetration and chemotherapeutic efficacy.

Single-ligand dual-targeting irinotecan liposomes: Control of targeting ligand display by pH-responsive PEG-shedding strategy to enhance tumor-specific therapy and attenuate toxicity.

Along with the malignant proliferation of tumor requiring nutrients, the expression of L-type amino acid transporter 1(LAT1) and amino acid transporter B0,+ (ATB0,+) in cancer cells is up-regulated that can be used as new targets for active targeting of tumor. However, since normal cells also express amino acid transporters in small amounts, traditional ligand-exposure drug delivery systems are potentially toxic to the body. Therefore, we designed a smart-response drug delivery system that buries the tyrosine ligand in PEG hydration layer at normal tissues and exposes the ligand by cleaving the pH-sensitive bond of PEG at the tumor site. Irinotecan (CPT-11) is actively loaded into the inner aqueous phase of liposomes via a copper ion gradient mechanism which has high encapsulation efficiency and stable drug release profile. Smart-response liposomes showed the strongest cytotoxicity and the maximum cellular uptake in vitro, the largest amount of tumor site accumulation and the best antitumor effect in vivo, compared with non-targeted liposomes and non-sensitive liposomes. It is worth noting that smart-response liposomes not only achieved enhanced antitumor effect but also attenuated side effects compared to ligand-exposure liposomes. This provides a smart responsive drug delivery system for precise treatment and shows a good application prospect.

Redox responsive paclitaxel dimer for programmed drug release and selectively killing cancer cells

Redox stimulus responsive drug delivery systems have been widely investigated and proved to be promising prospects for efficient cancer therapy due to the abnormal high level of reactive oxygen species and glutathione in tumor microenvironment. Herein, three paclitaxel dimers (named as PTX2-R, R = S, Se and Te) bridged with alkyl sulfide, selenide or telluride are synthesized. These dimers can self-assemble into stable uniform nanoparticles (named as PTX2-R NPs, R = S, Se and Te) with impressively high drug loading. As expected, sulfur/selenium/tellurium bonds exhibit different redox responsiveness, thereby affecting the drug release and cytotoxicity. Of note, tellurium bridged paclitaxel dimer shows ultra-sensitivity to hydrogen peroxide, which rapidly cleaves into two paclitaxel under the subsequent dithiothreitol stimulation. Our findings provide deep insight into the redox sensitivity of chalcogenide elements and offer the rational design strategies to biologically redox condition for programmed drug release.

PH‐responsive chitosan/sulfobutyl ether‐β‐cyclodextrin supramolecular nanoparticles for controlled release of sodium ferulate

AbstractA pH‐responsive supramolecular nanoparticles was constructed through the electrostatic interaction from anionic sulfobutyl ether‐β‐cyclodextrin (SBE7‐β‐CD) and two positively charged chitosan (CS‐75% and CS‐95%). The prepared nanoparticles were characterized by UV‐vis absorption spectra, x‐ray diffraction, dynamic light scattering, transmission electron microscopy, and zeta potential. It was found that the CS/SBE7‐β‐CD nanoparticles can be disassembly by increasing pH value and reassembled by reducing to the original pH value. To explore the potential of the obtained nanoparticles as a drug delivery vehicle, a negatively charged anticardio cerebrovascular drug sodium ferulate (SF) was loaded. The result indicated that the SF could be efficiently encapsulated in its nanoparticle nucleus under simulated gastric conditions with lower pH (pH 2.0), while effective release is triggered in a simulated intestinal environment with higher pH (pH 8.5). The assembly/disassembly behavior and drug loading/release property make CS/SBE7‐β‐CD nanoparticles promising candidates for pH stimulation responsive drug delivery system, which has a broad application prospect in the treatment of cardiovascular and cerebrovascular diseases, diabetes and other chronic diseases.

Investigation of controlled release properties and anticancer effect of folic acid conjugated magnetic core–shell nanoparticles as a dual responsive drug delivery system on A-549 and A-431 cancer cell lines

Epirubicin loaded on magnetite-coated calcium ferrite conjugated folic acid (Fe3O4@CaFe2O4-FA@EPI) was synthesized and characterized using various techniques like SEM, EDX, FT-IR, XRD, TGA, BET, and VSM. Also, the therapeutic effects on A-549 and A-431 cancer cell lines and delivering ability of Fe3O4@CaFe2O4-FA@EPI for potential use as a system of targeted drug delivery in cancer therapy were investigated. The obtained results show that these hybrid nanoscale particles have a large capacity of adsorption for EPI (19.4 wt.%) and desirable drug loading performance (97.5%). The acetate buffer environment guides the drug release to a higher amount (99%), in comparison with the phosphate-buffered saline (28%). Also, the Fe3O4@CaFe2O4-FA@EPI nanohybrids in vitro cytotoxic activity versus A-549 (null folate receptor) and A-431 (positive folate receptor) cancer cell lines in group III (Fe3O4@EPI) investigations, show the higher cell cytotoxicity and apoptosis in A-549 cells compared to A-431 (p < 0.05). Moreover, in A-431 cells, the percent of cell cytotoxicity and cell death grew in the Fe3O4@CaFe2O4-FA@EPI group in comparison with the A-549 cell line (p < 0.05). The results illustrated the effects of Fe3O4@CaFe2O4-FA@EPI group on cytotoxicity and apoptosis of A-431 positive folate receptor cancer cells were almost two times greater than free EPI. Furthermore, obtained findings show that the Fe3O4@CaFe2O4-FA@EPI provides a specific growth inhibition of cancer cells through binding to receptors on the cell membrane and intracellular uptake.

Core-Shell PVA/PVP-FeOOH Nanofibers as a Potential Visible Light Responsive Drug Delivery System

The high surface area per unit volume and core-shell configuration of electrospun nanofiber mat has a potential for drug delivery applications. Co-axial electrospinning technique resolves the limitation in the traditional transdermal drug delivery materials allowing to load a larger concentration of therapeutic agents per unit mass of the polymer. Encapsulating the drug in the fiber core provides protection and prolonged drug release. In the present study mats of core-shell PVA/PVP-FeOOH nanofibers were successfully formed by the coaxial electrospinning process for the first time. The visible light responsive FeOOH drug carrier material was incorporated in fiber core to provide non-invasive drug release on demand. The prepared materials posses visible light triggered release of organic methylene blue molecules.

Dual-stimuli responsive mesoporous copper (II) sulfide nanocomposite for chemo-photothermal synergistic therapy

A combination of chemo-photothermal therapy has recently emerged as a great potential cancer treatment due to enhanced therapeutic efficacy. Herein, we present a novel nanocomposite for chemo-photothermal synergistic therapy. The glutathione (GSH)-responsive mesoporous silica-coated copper sulfide (mesoporous CuS) nanocomposite was synthesized by co-condensation using tetraethyl orthosilicate (TEOS) and bis[3-(triethoxysilyl)propyl]tetrasulfide (BTES). Hyaluronic acid (HA) was functionalized on nanocarrier for drug leakage prevention, enzyme-triggered drug release and targeting moiety toward CD44 overexpressing cancer cells. The mesoporous CuS nanocomposite generated the heat for photothermal therapy in response to near-infrared (NIR) irradiation. The release of doxorubicin (Dox) from mesoporous CuS nanocomposite was controlled by dual-stimuli of response. We confirmed that mesoporous CuS nanocomposite was internalized to HeLa cells by CD44 receptor-mediated endocytosis and significantly enhanced anticancer effects due to the combination treatment. Therefore, we developed a tumor targeted dual-stimuli responsive drug delivery system for chemo-photothermal synergistic therapy. • GSH-responsive mesoporous silica coated CuS nanocomposites was prepared by in-situ co-condensation method using TEOS and BTES. • HA was functionalized on nanocarrier as a gate keeper and CD44 receptor targeting moiety. • Mesoporous CuS nanocomposite exhibited good photothermal effect and dual stimuli-responsive durg release property by GSH and HAase. • Mesoporous CuS nanocomposite enhanced therapeutic efficacy against cancer cell by chemo-photothermal combination treatment.

Synthesis and characterization of a pH responsive and mucoadhesive drug delivery system for the controlled release application of anti-cancerous drug

In this work a novel pH sensitive composite, polyacrylamide grafted succinyl chitosan intercalated bentonite (AAm-g-NB/SC) was prepared as a drug carrier system for the controlled delivery of paclitaxel. Characterization of the drug delivery system was carried out using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal analysis etc. The equilibrium swelling behaviour of the composite was studied and the result showed a maximum at pH 7.4. The in vitro drug release study of paclitaxel indicated that about 15.6% of drug release was found to be occurred at pH 1.2 within 16 h, whereas about 82.5% of drug release was occurred at the intestinal pH condition of 7.4. In vitro biocompatibility study was performed and the result showed good biocompatibility of the composite in the concentration range 6.25–100 µg/mL. The cytotoxicity assay was carried out in cancerous cell line of Human colorectal Adenocarcinoma. Mucous glycoprotein assay study showed that the drug delivery system having good apparent adhering property towards mucin. The investigation indicated that paclitaxel, an anticancer drug can be successfully entrapped in the AAm-g-NB/SC composite for the controlled and targeted delivery for colorectal cancer therapy.

Multi-stimuli responsive mesoporous silica-coated carbon nanoparticles for chemo-photothermal therapy of tumor

In this work, a traceable dual-porous mesoporous silica-coated mesoporous carbon nanocomposite (MCN@Si) with high drug loading capacity and high photothermal conversion efficiency (30.5 %) was successfully prepared. Based on the nanocomposite, a pH/redox/near infrared (NIR) multi-stimuli responsive drug delivery system was constructed to realize the accurate drug delivery, drug controlled release and chemo-photothermal synergistic antitumor therapy. MCN@Si was used as a vehicle to load doxorubicin (DOX) with a high drug loading efficacy of 48.2 % and a NIR absorbance agent for photothermal therapy and NIR thermal imaging. Carbon dots (CDs) with proper size were covalently attached to the surface of MCN@Si via disulfide bonds to block the mesopores, preventing DOX premature release from DOX/MCN@Si-CDs. Besides, CDs were served as fluorescent probe to prove the visualization potential of the drug delivery system. DOX was rapidly released at the condition of low pH and high GSH concentration due to the breakage of disulfide bonds and protonation of DOX. Moreover, the local hyperthermia generated by MCN@Si-CDs under NIR irradiation could not only directly kill cells, but also accelerate DOX release and enhance cells sensitivity and permeability. Two-dimensional cells and three-dimensional tumor spheroids assays illustrated that DOX/MCN@Si-CDs + NIR group exhibited a superior thermochemotherapy synergistic treatment effect and the combination index (CI) was 0.378. Biodistribution study showed the biosecurity of preparations and its prolonged detention time in tumor sites. Besides, antitumor experiment in vivo also performed the excellent synergistic inhibition effect. All the results demonstrated that DOX/MCN@Si-CDs is a traceable multi-stimuli responsive nanodelivery system and can achieve efficient chemo-photothermal synergistic antitumor therapy.

A Review on pH and Temperature Responsive Gels in Drug Delivery

Anticancer drugs play important roles in cancer treatment. However, these drugs have many disadvantages such as poor solubility, high toxicity, and serious side effects like hair loss, nausea and vomiting, anemia etc. To overcome these drawbacks, many attempts have been made to develop novel controlled drug delivery systems. They can encapsulate the drug and release it to the cancer site without leaking into other sites. The employment of multi-responsive hydrogels as a drug delivery system have some advantages over other drug delivery systems due to their ease of preparation, high efficiency, high-water content, tunable physical, and biological properties. The most advantages of these hydrogels is the volume phase transitions in their cross-linked three-dimensional networks as exposure to external stimuli such as temperature, pH, pressure, electric field, magnetic field and light. There has been research on other drug delivery systems which can respond to changes in pH and temperature for targeted drug release. Among those,gels have been studied mostly for their dual responsiveness. This provides an update on progress of gel based dual pH and temperature responsive drug delivery systems. Various systems under these categories for targeted and controlled delivery of different classes of drugs such as ant diabetic and antibiotic drugs with special emphasis on anticancer drugs are discussed in this review.

Nano mesoporous silica for cancer treatment: ROS-responsive and redox-responsive carriers

Reactive oxygen species ROS and redox agents are two features of cancer medium, which could be used through responsive drug delivery systems for cancer treatment. Furthermore, mesoporous silica nanoparticles (MSNs) have special characteristics to use them in ROS-responsive and redox-responsive carriers. To shed light on this issue, we propose two drug delivery systems: 1) responsive to hydrogen peroxide (a ROS component) and 2) responsive to dithiothreitol (a redox agent). The proposed carriers are composed of 4 parts: MSNs, responsive agent (selenocystine for ROS-responsive and dithiodipropionic for the redox-responsive carrier), hyaluronic acid as the coating and targeting agent, and the fourth part is the cancer drug. The result of this study showed there is more than 50% difference in drug release difference in a medium with stimuli and a medium without stimuli. Furthermore, the drug release profiles are concentration-dependent of the stimuli. These results confirm the smart behavior of the proposed carriers in different media. The results of this study pave the way for the utilization of MSNs in ROS-responsive and redox-responsive carriers.

Fabrication of versatile dynamic hyaluronic acid-based hydrogels

In this study, an injectable and self-healing hydrogel based on the boronic ester dynamic covalent bond between phenylboronic acid modified hyaluronic acid (HA-PBA) and the commercially available poly (vinyl alcohol) (PVA) is prepared and should have multi-functions for biomedical applications. The hydrogels were rapidly formed under mild conditions, and the rheological properties and in vitro degradation were systematically characterized. The HA-based hydrogels possessed good injectability and self-healing properties because of the dynamic bond. Moreover, due to the sensitivity of boronic ester to the biologically relevant concentration of hydrogen peroxide (H2O2), a major reactive oxygen species (ROS), the injectable hydrogel could be used as a H2O2/ROS responsive drug delivery system. The hydrogels supported good viability of encapsulated neural progenitor cells (NPC) and protected NPC from ROS induced damage in vitro when H2O2 was present in the media. The dynamic hydrogels were further applied as bio-inks for 3D printing/bioprinting. Overall, this facilely prepared dynamic hydrogel based on HA-PBA and PVA may have many potential biomedical applications, including drug delivery, 3D culture of cells, and 3D bioprinting.

"Smart" self-assembled structures: toward intelligent dual responsive drug delivery systems.

Combination of various polymeric blocks with distinct characteristics such as thermo-responsiveness, non-ionic nature and zwitterionic properties is an interesting approach toward fabricating copolymers undergoing a smart self-assembly process in an aqueous environment. In some cases, through a so-called "schizophrenic" self-assembly process, stimuli-induced self-assembly can occur from either double-hydrophilic or double hydrophobic polymers. In this process, the roles of the blocks forming the hydrophobic core and hydrophilic shell can be switched by changing the external conditions. This transformation in the solubilization profile leads to the fabrication of "smart" polymeric vehicles which could potentially control the release of their cargos as well as differentiate between encapsulated agents based on their charge and polarity properties. The aforementioned changes of the amphiphilicity of polymers in "schizophrenic" structures offer numerous self-assembly scenarios. In the current review, we summarize the polymer and peptide-based schizophrenic copolymers which could form micellar and vesicular (polymersome) systems providing novel structures with beneficial applications.

A two-photon responsive naphthyl tagged p-hydroxyphenacyl based drug delivery system: uncaging of anti-cancer drug in the phototherapeutic window with real-time monitoring.

We report a two-photon responsive drug delivery system (DDS), namely, p-hydroxyphenacyl-naphthalene-chlorambucil (pHP-Naph-Cbl), having a two-photon absorption (TPA) cross-section of ≥20 GM in the phototherapeutic window (700 nm). Our DDS exhibited both AIE and ESIPT phenomena, which were utilized for the real-time monitoring of anti-cancer drug release.

Echogenic Exosomes as ultrasound contrast agents.

Exosomes are naturally secreted extracellular bilayer vesicles (diameter 40–130 nm), which have recently been found to play a critical role in cell-to-cell communication and biomolecule delivery. Their unique characteristics—stability, permeability, biocompatibility and low immunogenicity—have made them a prime candidate for use in delivering cancer therapeutics and other natural products. Here we present the first ever report of echogenic exosomes, which combine the benefits of the acoustic responsiveness of traditional microbubbles with the non-immunogenic and small-size morphology of exosomes. Microbubbles, although effective as ultrasound contrast agents, are restricted to intravascular usage due to their large size. In the current study, we have rendered bovine milk-derived exosomes echogenic by freeze drying them in the presence of mannitol. Ultrasound imaging and direct measurement of linear and nonlinear scattered responses were used to investigate the echogenicity and stability of the prepared exosomes. A commercial scanner registered enhancement (28.9% at 40 MHz) in the brightness of ultrasound images in presence of echogenic exosomes at 5 mg mL−1. The exosomes also showed significant linear and nonlinear scattered responses—11 dB enhancement in fundamental, 8.5 dB in subharmonic and 3.5 dB in second harmonic all at 40 μg mL−1 concentration. Echogenic exosomes injected into the tail vein of mice and the synovial fluid of rats resulted in significantly higher brightness—as much as 300%—of the ultrasound images, showing their promise in a variety of in vivo applications. The echogenic exosomes, with their large-scale extractability from bovine milk, lack of toxicity and minimal immunogenic response, successfully served as ultrasound contrast agents in this study and offer an exciting possibility to act as an effective ultrasound responsive drug delivery system.

Intracellular Restructured Reduced Glutathione-Responsive Peptide Nanofibers for Synergetic Tumor Chemotherapy.

Self-assembled peptide nanofibers have been widely studied in cancer nanotherapeutics with their excellent biocompatibility and low toxicity of degradation products, showing the significant potential in inhibiting tumor progression. However, poor solubility prevents direct intravenous administration of nanofibers. Although water-soluble peptide precursors have been formed via the method of phosphorylation for intravenous administration, their opportunities for broad in vivo application are limited by the weak capacity of encapsulating drugs. Herein, we designed a novel restructured reduced glutathione (GSH)-responsive drug delivery system encapsulating doxorubicin for systemic administration, which achieved the intracellular restructuration from three-dimensional micelles into one-dimensional nanofibers. After a long blood circulation, micelles endocytosed by tumor cells could degrade in response to high GSH levels, achieving more release and accumulation of doxorubicin at desired sites. Further, the synergistic chemotherapy effects of self-assembled nanofibers were confirmed in both in vitro and in vivo experiments.

A new biosafe reactive oxygen species responsive nanoplatform for targeted oral squamous cell carcinoma therapy

A new reactive oxygen species (ROS)-responsive drug delivery systems (DDSs) needs development and has excellent application prospect. In this study, FA-PEG-TK-PLGA copolymer containing a ROS-responsive TK linker was designed and generated. The polymer self-assembled into stable small-sized DDSs into with hydrophilic PEG shells and hydrophobic PLGA cores, which exhibited high stability in aqueous solutions, besides an adequate drug loading capacity, excellent ROS sensitivity. high stability and good compatibility. Folic acid (FA) in the DDS presented here was used to target cancer cells. The polymer presents great potential as a novel DDSs for Oral squamous cell carcinoma (OSCC) therapy.

Fabrication and Antitumor Mechanism of a Nanoparticle Drug Delivery System: Graphene Oxide/Chitosan Oligosaccharide/γ‐Polyglutamic Acid Composites for Anticancer Drug Delivery

AbstractThis study focused on the design of a novel pH responsive nanoparticle drug delivery system (NDDS) with high biocompatibility and water solubility. The designed system was used for doxorubicin (DOX) delivery at tumor sites in a controlled manner. These innovative nanoparticles are soluble in physiological solutions besides water. In this study, pretreated γ‐polyglutamic acid (γ‐PGA) aqueous solutions were loaded into composites of graphene oxide (GO) covalently linked with chitosan oligosaccharide (CO) to fabricate GO‐CO‐γ‐PGA via amidation. The characterizations of the synthesized samples were carried out by using fourier transform infrared spectrometer (FTIR), X‐ray photoelectron spectrometer (XPS), ultraviolet– visible spectrophotometer (UV‐Vis), transmission electron microscopy (TEM), atomic force microscope (AFM) and zeta potential. Furthermore, drug loading and release behaviors from GO‐CO‐γ‐PGA were studied. The DOX loading in the constructed nanocarriers (GO‐CO‐γ‐PGA‐DOX) resulted in controlled and sustained release. The results of cell experiments revealed that the synthesized composites, which were easily transferred into cells, showed low toxicity and exhibited excellent antitumor effect due to its good connection with DOX. In addition, the composite nanoparticles caused the cell cycle arrest of Hela cells at the G2/M phase. Western blot results indicated that GO‐CO‐γ‐PGA‐DOX downregulated the expression of Bcl‐2 protein but upregulated Bax protein expression, which triggered the release of cytochrome C (Cytc). This condition further activated caspase‐3, cleaved the substrate of poly ADP‐ribose polymerase (PARP), and caused cell apoptosis. These results demonstrated that GO‐CO‐γ‐PGA‐DOX induces apoptosis via the intrinsic mitochondrial apoptotic pathway. Hence GO‐CO‐γ‐PGA composites have promising application in the field of biomedicine.

Liposomes with pH responsive ‘on and off’ switches for targeted and intracellular delivery of antibiotics

pH responsive drug delivery systems are one of the new strategies to address the spread of bacterial resistance to currently used antibiotics. The aim of this study was to formulate liposomes with ‘On’ and ‘Off’’ pH responsive switches for infection site targeting. The vancomycin (VCM) loaded liposomes had sizes below 100 nm, at pH 7.4. The QL-liposomes had a negative zeta potential at pH 7.4 that switched to a positive charge at acidic pH. VCM release from the liposome was quicker at pH 6 than pH 7.4. The OA-QL-liposome showed 4-fold lower MIC at pH 7.4 and 8- and 16-fold lower at pH 6.0 against both MSSA and MRSA compared to the bare drug. OA-QL liposome had a 1266.67- and 704.33-fold reduction in the intracellular infection for TPH-1 macrophage and HEK293 cells respectively. In vivo studies showed that the amount of MRSA recovered from mice treated with formulations was 189.67 and 6.33-fold lower than the untreated and bare VCM treated mice respectively. MD simulation of the QL lipid with the phosphatidylcholine membrane (POPC) showed spontaneous binding of the lipid to the bilayer membrane both electrostatic and Van der Waals interactions contributed to the binding. These studies demonstrated that the ‘On’ and ‘Off’ pH responsive liposomes enhanced the activity targeted and intracellular delivery VCM.

"Two in one": Simultaneous functionalization and DOX loading for fabrication of nanodiamond-based pH responsive drug delivery system.

Nanodiamond (ND) has been widely studied as a new type of carbon nanomaterials that is expected to be used as a promising candidate in various fields especially in the field of biomedicine. However, its poor water dispersibility and insufficient controlled release limit its practical applications. In this paper, ND-based composites with pH-responsive hydrazone bonds were successfully prepared by a simple chemical reaction between ester groups and hydrazine hydrate, in which ester groups were conjugated on the surface of ND via thiol-ene click reaction. On the other hand, CHO-PEG and doxorubicin hydrochloride (DOX) were linked on the carriers through formation of hydrazone bonds, resulting in improving water dispersibility and high drug loading capacity. The structure, thermal stability, surface morphology and particle size of ND carriers were characterized by different equipment. Results demonstrated that we have successfully prepared these functionalized ND. The release rate of DOX in acidic environment was significantly greater than that in normal physiological environment. More importantly, cell viability and optical imaging results showed that ND-based composites possess good biocompatibility, therapeutic effect, and could successfully transport DOX to HepG2 cells. Considering the above results, we believe that our new ND carriers will become promising candidates for intracellular controlled drug delivery and cancer treatment.