Mesoporous silica nanoparticle core-shell matrix (MSN CSM) engineered by green approach for pH triggered release of anticancer drugs

The present work exhibits an alternative route to design a nano-carrier using simple electrostatic interactions of biopolymeric layers on Mesoporous Silica Nanoparticle surface using Layer by Layer (LbL) technique. The doxorubicin (DOX) loaded MSN nano-carrier is coated with positively charged chitosan followed by a coating of negatively charged sodium carboxymethyl cellulose (Na-CMC) to form a DOX-loaded MSN Core-Shell Matrix (DOX-MSN CSM). The prepared MSN nano-carrier exhibits a high encapsulation efficiency of DOX (～93 %) due to its porous nature (～832 m²/gm) and negative surface charge (-21.5 mV). It exhibits a controlled release of DOX (～21 %) at physiological pH (7.4 pH) and improved drug release (～67 %) at cancer cells pH (5.4 pH) after 48 h. Further, the in-vitro cell line study using MDA-MB 231 cells reconfirms the slower and controlled release of DOX from the engineered DOX-MSN CSM. The confocal microscopy result shows that the DOX is internalized via endocytosis into the nucleus of the cells. The cell viability assay confirms more cells viable (～76 %) for DOX-MSN CSM than free DOX (～49 %) at the end of 24 h. The present study shows an alternate route to the conventional complex multi-step processes such as coupling reactions or chemical crosslinkers involving solvents. The proposed MSN core–shell matrix can be a potential nano-carrier for cancer drug delivery.     

In vitro evaluation of folic acid modified carboxymethyl chitosan nanoparticles loaded with doxorubicin for targeted delivery

The development of smart targeted nanoparticle that can deliver drugs to direct cancer cells, introduces better efficacy and lower toxicity for treatment. We report the development and characterizations of pH-sensitive carboxymethyl chitosan modified folic acid nanoparticles and manifest their feasibility as an effective targeted drug delivery vehicle. The nanoparticles have been synthesized from carboxymethyl chitosan with covalently bonded bifunctional 2,2′-(ethylenedioxy)-bis-(ethylamine) (EDBE) through the conjugation with folic acid. The conjugation has been analyzed by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The resultant nanoparticles with an average size less then 200 nm measured by dynamic light scattering and transmission electron microscopy. Confocal microscopy and flow cytometric analysis have revealed that folate-mediated targeting significantly enhances the cellular uptake of the nanoparticle and thus facilitates apoptosis of cancer cells (HeLa, B16F1). For the application of the nanoparticles as a drug carrier, Doxorubicin a potent anticancer drug has been loaded into the nanoparticles, with the drug loading amount and the drug release pattern observed.     

Preparation and evaluation of oleoyl-carboxymethy-chitosan (OCMCS) nanoparticles as oral protein carriers

Oleoyl-carboxymethy chitosan (OCMCS) nanoparticles based on chitosan with different molecular weights (50, 170 and 820 kDa) were prepared by self-assembled method. The nanoparticles had spherical shape, positive surface charges and the mean diameters were 157.4, 274.1 and 396.7 nm, respectively. FITC-labeled OCMCS nanoparticles were internalized via the intestinal mucosa and observed in liver, spleen, intestine and heart following oral deliverance to carps (Cyprinus carpio). Extracellular products (ECPs) of Aeromonas hydrophila as microbial antigen was efficiently loaded to form OCMCS–ECPs nanoparticles and shown to be sustained release in PBS. Significantly higher (P < 0.05) antigen-specific antibodies were detected in serum after orally immunized with OCMCS-ECPs nanoparticles than that immunized with ECPs alone and non-immunized in control group in carps. These results implied that amphiphilic modified chitosan nanoparticles had great potential to be applied as carriers for the oral administration of protein drugs.     

Preparation and Optimization of Dry PLGA Nanoparticles by Spray Drying Technique

The aim of this article was to evaluate the potential of poly lactide-coglycolide (PLGA) nanoparticles (NPs) as carriers for controlling release of doxorubicin (DOX) via a spray drying technique. The challenge was to entrap a hydrophilic molecule into a lipophilic core molecule of PLGA. To achieve this objective, we modified conventional approach of drug loading to spray drying technique. The eight formulations of nanoparticles were prepared by modified double emulsion and solvent evaporation technique followed by spray drying using 2³ factorial designs. PLGA (A) and PVA (B) and stirring speed (C) were used as independent variables where particle size (Y₁), entrapment efficiency (Y₂) and percentage of drug release at the 32 hour (Y₃) were taken as dependant variables. The results showed that the method is easy and efficient for the entrapment of the drug as well as the formation of spherical nanoparticles. This modification improved DOX entrapment efficiency relative to controls real loadings up to 40%. The in vitro release studies indicated the DOX loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of DOX-PLGA nanoparticles.     

Synthesis and characterization of thiolated carboxymethyl chitosan-graft-cyclodextrin nanoparticles as a drug delivery vehicle for albendazole

A new strategy for the synthesis of thiolated carboxymethyl chitosan-g-cyclodextrin nanoparticles by an ionic-gelation method is presented. The synthetic approach was based on the utilization of 1,6-hexamethylene diisocyanate during cyclodextrin grafting onto carboxymethyl chitosan. The use of the 1,6-hexamethylene diisocyanate resulted in reactions between cyclodextrin and active sites at the C₆-position of chitosan, and preserved amino groups of chitosan for subsequent reactions with thioglycolic acid, as the thiolating agent, and tripolyphosphate, as the gelling counterion. Various methods such as scanning electron microscopy, rheology and in vitro release studies were employed to exhibit significant features of the nanoparticles for mucosal albendazole delivery applications. It was found that the thiolated carboxymethyl chitosan-g-cyclodextrin nanoparticles prepared using an aqueous solution containing 1 wt% of tripolyphosphate and having 115.65 (μmol/g polymer) of grafted thiol groups show both the highest mucoadhesive properties and the highest albendazole entrapment efficiency. The latter was confirmed theoretically by calculating the enthalpy of mixing of albendazole in the above thiolated chitosan polymer.     

Investigation of polymeric amphiphilic nanoparticles as antitumor drug carriers

In this paper, polymeric amphiphilic nanoparticles based on oleoyl–chitosan (OCH) with different degrees of substitution (DS, 5%, 11% and 27%) were prepared by Oil/Water emulsification method. Mean diameters of the nanoparticles were 327.4 nm, 255.3 nm and 192.6 nm, respectively. Doxorubicin (DOX) was efficiently loaded into OCH nanoparticles and provided a sustained released after a burst release in PBS. These nanoparticles showed no cytotoxicity to mouse embryo fibroblasts (MEF) and low hemolysis rates (<5%). The results of SDS-PAGE indicated that bovine calf serum (BCS) adsorption on OCH nanoparticles was inhibited by smaller particle size. Cellular uptake was evaluated by incubating fluorescence labeled OCH nanoparticles with human lung carcinoma cells (A549) and mouse macrophages (RAW264.7). Cellular uptake of OCH nanoparticles was time––and concentration––dependent. Finding the appropriate incubation time and concentration of OCH nanoparticles used as drug carriers might decrease phagocytic uptake, increase cancer cell uptake and ultimately improve therapeutic efficiency of antitumor therapeutic agents.     

pH值响应性透明质酸纳米粒的制备及作为阿霉素载体的研究

通过化学交联法合成组氨酸修饰透明质酸耦合物(His-HA),制备载阿霉素纳米粒,分析其pH值响应性和抗肿瘤特征.研究显示,随着pH值的降低(7.4～5.5),纳米粒的粒径增大(230～780nm),zeta电位升高,载药纳米粒的体外释放量增加.细胞毒性实验显示粒径＜300nm的载药纳米粒具更高的毒性.细胞摄入实验表明,阿霉素通过受体介导的胞吞和载药纳米粒的胞外释放两种途径被细胞摄入.以上研究显示组氨酸修饰透明质酸纳米粒具有显著的pH值响应性,具备作为阿霉素药物载体的应用前景.     

Oral insulin delivery by self-assembled chitosan nanoparticles: In vitro and in vivo studies in diabetic animal model

We have developed self-assembled chitosan/insulin nanoparticles for successful oral insulin delivery. The main purpose of our study is to prepare chitosan/insulin nanoparticles by self-assembly method, to characterize them and to evaluate their efficiency in vivo diabetic model. The size and morphology of the nanoparticles were analyzed by dynamic light scattering (DLS), atomic force microscopy (AFM) and scanning electron microscopy (SEM). The average particle size ranged from 200 to 550 nm, with almost spherical or sub spherical shape. An average insulin encapsulation within the nanoparticles was ~ 85%. In vitro release study showed that the nanoparticles were also efficient in retaining good amount of insulin in simulated gastric condition, while significant amount of insulin release was noticed in simulated intestinal condition. The oral administrations of chitosan/insulin nanoparticles were effective in lowering the blood glucose level of alloxan-induced diabetic mice. Thus, self-assembled chitosan/insulin nanoparticles show promising effects as potential insulin carrier system in animal models.     

Anti-tumor activity of paclitaxel-loaded chitosan nanoparticles: An in vitro study

Chitosan nanoparticles containing the anticancer drug paclitaxel were prepared by a solvent evaporation and emulsification crosslinking method. The physicochemical properties of the nanoparticles were characterized by various techniques, and uniform nanoparticles with an average particle size of 116 ± 15 nm with high encapsulation efficiencies (EE) were obtained. Additionally, a sustained release of paclitaxel from paclitaxel-loaded chitosan nanoparticles was successful. Using different ratios of paclitaxel-to-chitosan, the EE ranged from 32.2 ± 8.21% to 94.0 ± 16.73 %. The drug release rates of paclitaxel from the nanoparticles were approximately, 26.55 ± 2.11% and 93.44 ± 10.96% after 1 day and 13 days, respectively, suggesting the potential of the chitosan nanoparticles as a sustained drug delivery system. Cytotoxicity tests showed that the paclitaxel-loaded chitosan had higher cell toxicity than the individual paclitaxel and confocal microscopy analysis confirmed excellent cellular uptake efficiency. TEM images showed the ultrastructure changes of A2780 cells incubated with paclitaxel-loaded nanoparticles. Flow cytometric analysis revealed two subdiploid peaks for the cells in the paclitaxel-loaded nanoparticles and paclitaxel treated groups, respectively, with the intensity of the former higher than that of the latter. Moreover, the cell cycle was arrested in the G₂-M phase, which was consistent with the action mechanism of the direct administration of paclitaxel. These results indicate that chitosan nanoparticles have potential uses as anticancer drug carriers and also have an enhanced anticancer effect.     

Doxorubicin loaded PVA coated iron oxide nanoparticles for targeted drug delivery

Magnetic drug targeting is a drug delivery system that can be used in locoregional cancer treatment. Coated magnetic particles, called carriers, are very useful for delivering chemotherapeutic drugs. Magnetic carriers were synthesized by coprecipitation of iron oxide followed by coating with polyvinyl alcohol (PVA). Characterization was carried out using X-ray diffraction, TEM, TGA, FTIR and VSM techniques. The magnetic core of the carriers was magnetite (Fe₃O₄), with average size of 10 nm. The room temperature VSM measurements showed that magnetic particles were superparamagnetic. The amount of PVA bound to the iron oxide nanoparticles were estimated by thermogravimetric analysis (TGA) and the attachment of PVA to the iron oxide nanoparticles was confirmed by FTIR analysis. Doxorubicin (DOX) drug loading and release profiles of PVA coated iron oxide nanoparticles showed that up to 45% of adsorbed drug was released in 80 h, the drug release followed the Fickian diffusion-controlled process. The binding of DOX to the PVA was confirmed by FTIR analysis. The present findings show that DOX loaded PVA coated iron oxide nanoparticles are promising for magnetically targeted drug delivery.     

Synthesis and characterization of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles

With the aim to develop a novel water-soluble modified chitosan nanoparticle with tuned size and improved antibacterial activity, quaternized carboxymethyl chitosan/poly(amidoamine) dendrimers (CM-HTCC/PAMAM) were synthesized. Firstly low-generation amino-terminated poly(amidoamine) (PAMAM) dendrimers were prepared via repetitive reactions between Michael addition and amidation, which were then employed for modifying quaternized carboxymethyl chitosan (CM-HTCC). Prior to the reaction of CM-HTCC with PAMAM, carboxylic groups in CM-HTCC were activated with EDC/NHS in order to enhance the reaction efficiency. FT-IR, ¹H NMR, elemental analysis and XRD were performed to characterize CM-HTCC/PAMAM dendrimers. Turbidity measurements showed that CM-HTCC/PAMAM dendrimers had good water-solubility. TEM images indicated that CM-HTCC/PAMAM dendrimers existed as smooth and spherical nanoparticles in aqueous solution. The results of antibacterial activity explored that CM-HTCC/PAMAM dendrimer nanoparticles displayed higher antibacterial activity against Gram-negative bacteria Escherichia coli (E. coli), whereas they showed much less efficiency against Gram-positive bacteria Staphylococcus aureus (S. aureus) compared to quaternized chitosan (HTCC).     

Investigating preparation and characterisation of diphtheria toxoid‐loaded on sodium alginate nanoparticles

This paper aims to investigate the preparation and characterisation of the alginate nanoparticles (NPs) as antigen delivery system loaded by diphtheria toxoid (DT). For this purpose, both the loading capacity (LC) and Loading efficiency (LE) of the alginate NPs burdened by DT are evaluated. Moreover, the effects of different concentrations of sodium alginate and calcium chloride on the NPs physicochemical characteristics are surveyed in addition to other physical conditions such as homogenization time and rate. To do so, the NPs are characterised using particle size and distribution, zeta potential, scanning electron microscopy, encapsulation efficiency, in vitro release study and FT‐IR spectroscopy. Subsequently, the effects of homogenization time and rate on the NPs are assessed. At the meantime, the NPs LC and efficiency in several DT concentrations are estimated. The average size of the NPs was 400.7 and 276.6 nm for unloaded and DT loaded, respectively. According to the obtained results, the zeta potential of the blank and DT loaded NPs are estimated as −23.7 mV and −21.2 mV, respectively. Whereas, the LC and LE were >80% and >90%, in that order. Furthermore, 95% of the releasing DT loaded NPs occurs at 140 h in the sustained mode without any bursting release. It can be concluded that the features of NPs such as morphology and particle size are strongly depended on the calcium chloride, sodium alginate concentrations and physicochemical conditions in the NPs formation process. In addition, appropriate concentrations of the sodium alginate and calcium ions would lead to obtaining the desirable NPs formation associated with the advantageous LE, LC (over 80%) and sustained in vitro release profile. Ultimately, the proposed NPs can be employed in vaccine formulation for the targeted delivery, controlled and slow antigen release associated with the improved antigen stability.     

Green synthesis of gold nanoparticles coated doxorubicin liposomes using procyanidins for light–controlled drug release

For the controlled drug release delivery system, gold nanomaterials have received considerable attention for their photothermal effect in medical applications. The exploration of green and facile methods for constructing efficient gold based nanomaterials to control drug release is greatly needed. Hence, we aim to prepare procyanidins (PCs) reduced gold nanoparticles (AuNPs) coated doxorubicin (DOX) liposomes (DOX–PCs–Lips@AuNPs), of which PCs were modified on phosphatidylcholine and acted as both reductant and stabilizer during the synthesis of AuNPs. As a result, AuNPs were successfully synthesized by PCs, so as to avoid the use of traditional reductants. The as prepared DOX–PCs–Lips@AuNPs were proved to have spherical shape, good photothermal property and controlled drug release behavior after 808 nm laser irradiation. As a green and facile synthesized nanomaterial, DOX–PCs–Lips@AuNPs would consolidate the medical application of AuNPs.     

Preparation of N-trimethyl chitosan-protein nanoparticles intended for vaccine delivery

In this paper, various N-trimethyl chitosan (TMC) of different molecular-weights (approximately 100 KD, approximately 200 KD, and approximately 400 KD, respectively) with the approximately degree of quartenization (DQ) of 40% were successfully synthesized. In vitro cytotoxicity of TMC solution showed the dependence of TMC concentration from 20 microg/ml to 500 microg/ml on the relative cell activity. Molecular weight of TMC did not greatly affect the cytotoxicity of TMC against HEK293 and L929 cells. TMC nanoparticles and alginate modified TMC nanoparticles were prepared by the ionic gelation method. Subsequently, we investigated the properties of TMC nanoparticles and alginate modified TMC nanoparticles intending for oral delivery of antigens. Molecular weight of TMC did not affect the loading capacity (LC) and in vitro release behavior of TMC nanoparticles. However, BSA concentration and alginate modification have strongly effect on properties of TMC nanoparticles (particle size; surface charge; loading efficiency and loading capacity). In vitro release behavior indicated that alginate modification could efficiently decrease initial burst release and extend release time in phosphate buffer (PBS, pH 7.4) and acidic solution (0.1 M HCl, pH = 1) at 37 degrees C. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) assay showed that alginate modification could effectively improve the stability of TMC nanoparticles and protect BSA from degradation or hydrolysis in acidic condition for at least 2 h.     

Amino Acid Metabolism Abnormity and Microenvironment Variation Mediated Targeting and Controlled Glioma Chemotherapy

Energy metabolism abnormity is one of the most significant hallmarks of cancer. As a result, large amino acid transporter 1 (LAT1) is remarkably overexpressed in both blood‐brain‐barrier and glioma tumor cells, leading a rapid and sufficient substrate transportation. 3CDIT and 4CDIT are originally synthesized by modifying the existing most potent LAT1 substrate. 3CDIT is selected as its higher glioma‐targeting ability. Since the microenvironment variation in tumor cells is another important feature of cancer, a great disparity in adenosine‐5′‐triphosphate (ATP) and glutathione (GSH) levels between extracellular and intracellular milieu can provide good possibilities for dual‐responsive drug release in tumor cells. Doxorubicin (DOX) is successfully intercalated into the ATP aptamer DNA scaffolds, compressed by GSH‐responsive polymer pOEI, and modified with 3CDIT to obtain 3CDIT‐targeting pOEI/DOX/ATP aptamer nanoparticles (NPs). Enhanced NP accumulation and rapid GSH & ATP dual‐responsive DOX release in glioma are demonstrated both in vitro and in vivo. More efficient therapeutic effects are shown with 3CDIT‐targeting pOEI/DOX/ATP aptamer NPs than free DOX and no systemic toxicity is observed. Therefore, glioma‐targeting delivery and GSH & ATP dual‐responsive release guarantee an adequate DOX accumulation within tumor cells and ensure a safe and efficient chemotherapy for glioma.     

PEG-grafted chitosan nanoparticles as an injectable carrier for sustained protein release

The development of injectable nanoparticulate “stealth” carriers for protein delivery is a major challenge. The objective of this work was to investigate the possibility of achieving the controlled release of a model protein, insulin, from PEG-grafted chitosan (PEG-g-chitosan) nanoparticles (mean diameter 150–300 nm) prepared by the ion gelation method. Insulin was efficiently incorporated into the nanoparticles, and reached as high as 38%. In vitro release showed that it could control the insulin release by choosing the composition, loading and release temperature. We observed that the composition of the nanoparticle surface (C/O ratio) increased from 2.40 to 3.23, with an increase in the incubation time. Therefore, we concluded that during this time, insulin release from PEG-g-chitosan nanoparticles followed a diffusion mechanism in which erosion was negligible. The experiments also demonstrated that PEG-g-chitosan helped to maintain the natural structure of the protein entrapped in the nanoparticles.     

A sustained release formulation of chitosan modified PLCL:poloxamer blend nanoparticles loaded with optical agent for animal imaging

The objective of this study was to develop optical imaging agent loaded biodegradable nanoparticles with indocynanine green (ICG) using chitosan modified poly(L-lactide-co-epsilon-caprolactone) (PLCL):poloxamer (Pluronic F68) blended polymer. Nanoparticles were formulated with an emulsification solvent diffusion technique using PLCL and poloxamer as blend-polymers. Polyvinyl alcohol (PVA) and chitosan were used as stabilizers. The particle size, shape and zeta potential of the formulated nanoparticles and the release kinetics of ICG from these nanoparticles were determined. Further, biodistribution of these nanoparticles was studied in mice at various time points until 24 h following intravenous administration, using a non-invasive imaging system. The average particle size of the nanoparticles was found to be 146 ± 3.7 to 260 ± 4.5 nm. The zeta potential progressively increased from - 41.6 to + 25.3 mV with increasing amounts of chitosan. Particle size and shape of the nanoparticles were studied using transmission electron microscopy (TEM) which revealed the particles to be smooth and spherical in shape. These nanoparticles were efficiently delivered to the cytoplasm of the cells, as observed in prostate and breast cancer cells using confocal laser scanning microscopy. In vitro release studies indicated sustained release of ICG from the nanoparticles over a period of seven days. Nanoparticle distribution results in mice showing improved uptake and accumulation with chitosan modified nanoparticles in various organs and slower clearance at different time points over a 24 h period as compared to unmodified nanoparticles. The successful formulation of such cationically modified nanoparticles for encapsulating optical agents may lead to a potential deep tissue imaging technique for tumor detection, diagnosis and therapy.     

Role of GABA and serotonin coupled chitosan nanoparticles in enhanced hepatocyte proliferation

The development of nanoparticles containing active molecules having improved stability, sustained release and maximum half life helps in cell proliferation result in enhanced tissue regeneration. Our study focuses on the use of Gamma amino butyric acid (GABA) and serotonin (5-HT) coupled chitosan nanoparticles for the active liver regeneration in male Wistar rats. The nanoparticles were prepared and the morphology was studied using SEM. The FT-IR spectra of the nanoparticles and the maximum encapsulation efficiency of GABA and 5-HT binding to chitosan nanoparticles were observed. The in vitro release studies provided the percentage release of GABA and 5-HT from the nanoparticles at different time intervals. The quantification of DNA and protein syntheses was done using [³H] thymidine and [³H] leucine uptake studies that determined the enhancement in hepatocyte proliferation. Our results project the role of GABA and 5-HT chitosan nanoparticles in the treatment of liver based diseases.     

Development and in vitro evaluation of surface modified poly(lactide-co-glycolide) nanoparticles with chitosan-4-thiobutylamidine

The objective of this study was to develop a nanoparticulate drug delivery system based on the surface modification of poly(lactide-co-glycolide) (PLGA) nanoparticles with a thiolated chitosan. PLGA nanoparticles were prepared by the emulsification-solvent evaporation method. Immobilization of chitosan to the surface of PLGA nanoparticles via amide bonds was mediated by a carbodiimide. Thiol groups were covalently bound to the chitosan surface of particles by reaction with 2-iminothiolane. Obtained nanoparticles were characterized in vitro regarding size, zeta potential, thiol group content, stability at different pH values, mucoadhesion, and drug release. Results demonstrated that the surface modification of PLGA nanoparticles with thiolated chitosan (chitosan-TBA) leads to nanoparticles of a mean diameter of 889.5 ± 72 nm and positive zeta potential of + 24.74 mV. The modified nanoparticles contained 7.32 ± 0.24 μmol thiol groups per gram nanoparticles. The size of nanoparticles was strongly influenced by the pH of the surrounding medium, being 925.0 ± 76.3 nm at pH 2 and 577.8 ± 66.7 nm at pH 7.4. Thiolated nanoparticles showed a 3.3-fold prolonged residence time on the mucosa and an unchanged release profile in comparison to unmodified PLGA nanoparticles. These data suggest that surface modified chitosan-TBA conjugate PLGA nanoparticles have the potential to be used as mucoadhesive drug delivery system.     

A pH-sensitive theranostics system based on doxorubicin conjugated with the comb-shaped polymer coating of quantum dots

A two-phase route was developed to form a new theranostics-based system. The comb polymer poly (glycidyl methacrylate)-graft-ethane diamine-graft-polyethylene glycol (PGMA-g-EDA-g-PEG) was used to modify the quantum dots (QDs) by the method of ligand exchange. Subsequently, due to a large amount of amino groups on the surface of QDs, the doxorubicin (DOX) was conjugated by amine bonds to form pH-sensitive drug release system. UV–vis transmission spectra and PL spectra showed that the nanoparticles maintained the optical properties of QDs and DOX. The transmission electron microscopy analysis indicated that QDs were well dispersed in water and still had small sizes (7 nm) after ligand exchange and conjugated with DOX. Then the thermogravimetric analysis (TGA) revealed that about 80 wt% comb-shaped polymers coated on the surface of QDs, and about 10 wt% QDs was in nanoparticles PGMA-g-EDA-g-PEG-QDs-DOX. In vitro release studies showed that PGMA-g-EDA-g-PEG -DOX and PGMA-g-EDA-g-PEG-QDs-DOX were pH sensitive. Findings from this study suggested that nanoparticles PGMA-g-EDA-g-PEG-QDs-DOX can be used in a new field combined both imaging and targeted therapy.