pH-sensitive Release Behavior Research Articles

Efficient delivery of curcumin by functional solid lipid nanoparticles with promoting endosomal escape and liver targeting properties

In the realm of intracellular drug delivery, overcoming the barrier of endosomal entrapment stands as a critical factor influencing the effectiveness of nanodrug delivery systems. This study focuses on the synthesis of an acid-sensitive fatty acid derivative called imidazole-stearic acid (IM-SA). Leveraging the proton sponge effect attributed to imidazole groups, IM-SA was anticipated to play a pivotal role in facilitating endosomal escape. Integrated into the lipid core of solid lipid nanoparticles (SLNs), IM-SA was paired with hyaluronic acid (HA) coating on the surface of SLNs loading with curcumin (CUR). The presence of IM-SA and HA endowed HA-IM-SLNs@CUR with dual functionalities, enabling the promotion of endosomal escape, and specifical targeting of liver cancer. HA-IM-SLNs@CUR exhibited a particle size of ∼228 nm, with impressive encapsulation efficiencies (EE) of 87.5 % ± 2.3 % for CUR. Drugs exhibit significant pH sensitive release behavior. Cellular experiments showed that HA-IM-SLN@CUR exhibits enhanced drug delivery capability. The incorporation of IM-SA significantly improved the endosomal escape of HA-IM-SLN@CUR, facilitating accelerated intracellular drug release and increasing intracellular drug concentration, exhibiting excellent growth inhibitory effects on HepG2 cells. Animal experiments revealed a 3.4-fold increase in CUR uptake at the tumor site with HA-IM-SLNs@CUR over the free CUR, demonstrating remarkable tumor homing potential with the tumor growth inhibition rate of 97.2 %. These findings indicated the significant promise of HA-IM-SLNs@CUR in the realm of cancer drug delivery.

Preparation and Characterization of pH-sensitive Doxorubicin Grafted Hyaluronic Acid Nano-micelles

Background: This study was done to achieve a new drug delivery system delivering two different chemotherapy molecules to the target tissue simultaneously. Significance: Co-delivery of chemotherapy medicines provides synergistic effects leading to lowering the dose of administered drugs and side effects. Methods: Doxorubicin (DOX) was introduced to water-soluble hyaluronic acid (Hyal) using 1-amino-3,3-diethoxy-propane (ADEP), as a pH-sensitive linker, to develop a new hydrophobic structure, i.e. Hyal-ADEP-DOX. The conjugates were grafted in three ratios (7.5%, 12.5%, and 20%) to Hyal and characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1HNMR). Cannabidiol (CBD) was physically loaded in the core of nano-micelles. Results: Prepared nano-micelles were analyzed for critical micelle concentration (CMC) particle size stability and drug release before and after loading the CBD. Hyal-ADEP-DOX-12.5 was the optimized ratio and had a mean diameter of 50 nm before loading the CBD and 120 nm after loading (observed by transmission electron microscopy). The release results showed that DOX releases slowly in physiological pH, and CBD has a burst release at acidic pH from Hyal-ADEP-DOX-12.5. These properties altogether make Hyal-ADEP-DOX nano-micelles, as a stimuli-sensitive nano-carrier, a potential candidate for hydrophobic anticancer agents’ co-delivery. Conclusion: The grafted DOX exhibited pH-sensitive release behavior, i.e. while 22.8% of the drug was released after 24 h at pH 5.5, and 5% was released after 24 h at pH 7.4. Hyal-ADEP-DOX due to its low CMC value, colloidal stability, slow drug release in physiological pH, and burst release in acidic pH Hyal-ADEP-DOX, is an excellent candidate as a carrier to co-deliver hydrophobic therapeutic agents to tumor tissues.

Pivalic acid based N-doped carbon dots for drug delivery and antioxidant behaviour

Heteroatom doped surface engineered carbon dots has immense potential not only in their fluorescent sensing but also in nanocarrier for drug molecules and antioxidant behavior. Herein, we report a one-step thermal coupling synthesis of carbon dots from pivalic acid and naturally abundant gelatin (PGCDs). The as-synthesized PGCDs exhibited excellent colloidal stability, biocompatibility, and antioxidant activity. The surface of PGCDs was further modified with anticancer drug molecules to assess their drug delivery capabilities. The drug-loaded PGCDs demonstrated sustained release profiles, indicating their potential for controlled drug delivery applications. For understanding the drug delivery mechanism, the cumulative release data have been fitted into Weibull and Higuchi model. The PGCDs also showed pH sensitive release behavior where acidic environment has a better control in release profile compared to the alkaline pH. The concentration dependent radical activity shows more than 80% activity at below 1 mg/mL PGCDs concentration. Their low toxicity against live human cell lines could promote this PGCDs as a potential versatile nano-vector biomedical research area.

Eco-Friendly Fumed Nanosilica@Nanodiamond Hybrid Nanoparticles with Dual Sustainable Self-Healing and Barrier Anticorrosive Performances in Epoxy Coating.

Fumed nanosilica@nanodiamond attached by APTES [(3-aminopropyl) triethoxysilane], named FSiO2@sND, was examined as an efficient anticorrosive nanohybrid for epoxy coating. Compared with fumed nanosilica (FSiO2), nanodiamond (ND) moderated the hydrophilic nature of FSiO2@sND and offered additional functional groups to the nanohybrid, i.e., carboxylic groups of ND and functional groups of APTES, while retaining the eco-friendly nature of FSiO2 in the hybrid nanoparticle. The hybrid nanoparticle showed pH-sensitive release behavior in which APTES is released considerably in an alkaline medium, acting as an efficient corrosion inhibitor. A thorough electrochemical impedance spectroscopy (EIS) study of scratched coatings in a 3.5% NaCl solution disclosed that FSiO2@sND nanoparticles (at 0.33 wt % loading) conferred significant active/self-healing anticorrosion properties for the epoxy coatings, thanks to the release of APTES and the presence of carboxylic groups of ND taking part in forming a stable protective film on the substrate. Accordingly, epoxy/FSiO2@sND coatings showed a corrosion improvement efficiency of 138% at an optimum immersion time of 5 h, which was higher than the 96% improvement for epoxy/FSiO2 coating. Epoxy/FSiO2@sND intact coating showed much higher low-frequency impedance, i.e., 7.23 Ω·cm2, compared with epoxy/FSiO2 coating, i.e., 5.44 Ω·cm2, and neat epoxy coating, i.e., 5.71 Ω·cm2, after 22 weeks of immersion in salty solution. This result along with a detailed analysis of EIS data for intact coatings suggested that FSiO2@sND brought about strong barrier anticorrosive performance for epoxy coating. Such behavior was attributed to improved dispersion of nanohybrid in the epoxy matrix, enhanced cross-link density of the epoxy matrix, and improved coating/substrate adhesion caused by APTES and the carboxylic groups of ND.

A targeted biosystem based on l-lysine coated GO@rod-Cu(II) metal-organic frameworks for pH-controlled co-delivery of doxorubicin and curcumin

Breast cancer is a leading cause of mortality in women worldwide and has attracted substantial research interest in the past several decades. Among the various cancer treatment methods, doxorubicin (DOX) and curcumin (CUR) are the most effective chemotherapeutic drugs to treat breast cancer. However, the remarkable side effects and systemic toxicity recorded by chemotherapeutic drugs mainly due to their lack of selectivity for cancer cells, short blood half-life, and nonspecific targeting, often lead to the failure of chemotherapy. Hence, the purpose of this work is to fabricate a new pH-controlled biosystem based on l-lysine amino acid coating on the surface of magnetic graphene oxide@rod-Cu(II) metal-organic frameworks (GO-Fe3O4@Cu MOFs-Lys) to overcome these challenges. The GO-Fe3O4@Cu MOFs and GO-Fe3O4@Cu MOFs-Lys encapsulation efficiency for DOX and CUR was 78.25%, 28.16%, 98.35%, and 45.78%, respectively. The in vitro simultaneous releasing of drugs revealed a controlled and pH-sensitive release behavior of GO-Fe3O4@Cu MOFs-Lys for DOX and CUR. Meanwhile, the drug release mechanism confirmed a Fickian diffusion-controlled release of drugs based on the Korsmeyer-Peppas model. The results of the in vitro cytotoxicity via MTT demonstrated the acceptable biocompatibility of the GO-Fe3O4@Cu MOFs-Lys against MCF-7 and MCF-10A cells and its MCF-7 cancer cell-killing capability after simultaneous loading of DOX and CUR. In addition, the in vitro hemolysis and antioxidant activity investigation revealed that the GO-Fe3O4@Cu MOFs-Lys had good haemocompatibility and excellent antioxidant activity. These results promoted us that the GO-Fe3O4@Cu MOFs-Lys as a new pH-sensitive biosystem could achieve a controlled release to oral drug delivery.

Ultrasound-assisted synthesis layered double hydroxide@hydroxyapatite-doxorubicin coated magnetic PEG nanocomposite: A biocompatible pH-sensitive nanocarrier for anticancer drug delivery

In this study, a biocompatible pH-sensitive system was designed based on a nano-composition of layered double hydroxide@hydroxyapatite-doxorubicin coated magnetic Fe3O4-polyethylene glycol (LDH@HAp-DOX@Fe3O4-PEG) for targeted anticancer drug delivery. The prepared nanocomposites were thoroughly characterized using various techniques. The drug encapsulation efficiency (DEE) and drug-loading content (DLC) were calculated to be ∼ 78.1 % and 7.8 % for HAp-DOX, respectively. The kinetics and in-vitro drug release studies showed that LDH@HAp-DOX@Fe3O4-PEG has a controlled release profile compared to LDH@HAp-DOX at pH 5. Alternatively, the higher drug release rate (∼68.9 %) at a low-pH environment (pH 5) than that of pH 7.4 (≤40 %) confirmed a pH-sensitive release behavior of LDH@HAp-DOX@Fe3O4-PEG. In-vitro cytotoxicity and DAPI staining analyses showed that the LDH@HAp-DOX@Fe3O4-PEG has higher toxicity (cell viability ≤ 20 % at 31.25 μg/mL) than free DOX against MCF-7 breast cancer cells. In addition, the hemolysis assay confirmed the non-hemolytic nature (≤5%) of the LDH@HAp-DOX@Fe3O4-PEG nanocarrier. Based on the obtained results, the designed nanocomposite could be proposed as a promising candidate for the targeted DOX delivery by minimizing its possible side effects.

Construction of multifunctional targeted nano-prodrugs based on PAMAM dendrimers for tumor therapy

Nanomaterial-based drug delivery systems have demonstrated powerful applications in tumor therapy. PAMAM dendrimers by virtue of multivalent modification and biocompatible components were widely used to construction multifunctional targeted chemotherapeutics. In this report, we present a PAMAM dendrimer-based nano-prodrug delivery system for targeted tumor therapy. The RGDyC-PEG-PAMAM-PBA-Res (RPPPR) nano-prodrug was characterized by 1H NMR, zetasizer, and TEM, the drug loading and pH-sensitive drug release behaviors were investigated. In vitro cell viability assay revealed that the group treated with the nano-prodrug exhibited lower cell viability compared to the control group as concentration increased, confirming the nano-prodrug’s effectiveness in treating tumors. In vitro studies on cellular uptake of the nano-prodrug demonstrated that RPPPR had a high targeting ability, primarily attributed to the RGD-mediated target effect. Relevant data from our hemolysis assay indicated that the nano-prodrug maintained good blood compatibility within the concentration range of 0.1 to 0.3 mg/mL. In vivo experiments focusing on tumor therapy showed that RPPPR suppressed tumor growth and promoted tumor apoptosis. H&E staining, TUNEL assay, and immunohistochemistry results further validated the enhanced therapeutic effect. Importantly, no toxicity was observed in the vital organs such as the heart, liver, lung, kidneys, or spleen. These results suggest the superior antitumor efficacy of RPPPR compared to Resveratrol alone, and thus may be useful for tumor therapy. It is expected to explore new directions to establish a general strategy with dendritic prodrugs for synergistic tumor targeting therapy.

Ph-Responsive Alendronic Acid-Coated Liposomes for Improved Treatment Osteosarcoma

Objective Current research work aimed to develop pH-responsive osteosarcoma-targeted liposomes composed of non-oncology drugs previously identified for repositioning purposes. Material and Methods Using thin film hydration method, the Ketoconazole (KCZ)-, Simvastatin (SVN)-, and Niclosamide (NSD)-loaded non-targeted liposomes (KLs, SLs, and NLs respectively) were developed individually. The Aledronic acid-Choleteryl hemiscuccinate conjugate (AA-CHSC) was synthesized and confirmed using FTIR and 1H-NMR analysis. The AA-CHSC coated liposomes (pH sensitive and targeted liposome: PT-KLs, PT-SLs, and PT-NLs) were developed individually for the treatment of osteosarcoma with improved efficacy and reduced drug’s primary effects. The developed non-targeted and targeted liposomes were characterized for drug contentt,vesicle size, surface morphology using transmission electron microscope (TEM), in vitro pH-sensitive drug release behaviour using dialysis bag technique, and in vitro cytotoxicity characteristics against osteosarcoma cells. Results All non-targeted liposomes showed %drug content and mean vesicle size in the range of 41-75% and 161-182 nm, respectively. The AA-CHSC insertion into the liposomal membrane (targeted liposomes) has substantially improved the drug solubility in the membrane as a result of its amphiphilic nature. Furthermore, the targeted liposomes showed moderately increased mean vesicle size (203-210 nm) validating the surface modification. The TEM image revealed the formation of spherical, nearly spherical, and non-aggregated liposomes. The AA-CHSC insertion also caused liposomes sensitive to tumor pH (5.8); as a result, substantially higher drug release (58-80%) was observed as compared to non-targeted liposomes (34-52%). The cytotoxicity study results revealed substantially higher osteosarcoma cell (Saos-2) growth inhibition characteristics of targeted liposomes. Conclusions In conclusion, the developed targeted liposomes have potential application in the treatment of osteosarcoma. In addition, detailed anticancer activities should be revealed for the combination of targeted liposomes as the combination caused almost similar cytotoxicity as that of individual targeted liposomes.

Amine-functionalized polysilsesquioxane hollow nanospheres for pH-responsive pesticide release system with UV-shielding property

Polysilsesquioxane (PSQ) hollow spheres show great potential in various fields, including catalysts, environmental protection, and drug delivery, owing to their high stability, large interior cavity, and adjustable surface chemistry. However, the fabrication of amino-functionalized PSQ hollow spheres (AHPSQ) with inherent amine groups on the surface still remains a challenge partly due to the hydrophilicity of the silane precursor. In this study, for the first time AHPSQ was fabricated via a facile sol-gel process utilizing aminopropyltrimethoxysilane and methyltrimethoxysilane as co-precursor in an ice bath. The pH-sensitive release behavior of AHPSQ was demonstrated using avermectin as a pesticide model and the release kinetics were analyzed. The artificial ultraviolet accelerated experiment confirmed that the carrier has an ultraviolet protective effect on the pesticide and can reduce the ultraviolet degradation rate.

Antiviral and Antibacterial Sulfated Polysaccharide–Chitosan Nanocomposite Particles as a Drug Carrier

Drug delivery system (DDS) refers to the method of delivering drugs to the targeted sites with minimal risk. One popular strategy of DDS is using nanoparticles as a drug carrier, which are made from biocompatible and degradable polymers. Here, nanoparticles composed of Arthrospira-derived sulfated polysaccharide (AP) and chitosan were developed and expected to possess the capabilities of antiviral, antibacterial, and pH-sensitive properties. The composite nanoparticles, abbreviated as APC, were optimized for stability of morphology and size (~160 nm) in the physiological environment (pH = 7.4). Potent antibacterial (over 2 μg/mL) and antiviral (over 6.596 μg/mL) properties were verified in vitro. The pH-sensitive release behavior and release kinetics of drug-loaded APC nanoparticles were examined for various categories of drugs, including hydrophilic, hydrophobic, and protein drugs, under different pH values of the surroundings. Effects of APC nanoparticles were also evaluated in lung cancer cells and neural stem cells. The use of APC nanoparticles as a drug delivery system maintained the bioactivity of the drug to inhibit the proliferation of lung cancer cells (with ~40% reduction) and to relieve the growth inhibitory effect on neural stem cells. These findings indicate that the pH-sensitive and biocompatible composite nanoparticles of sulfated polysaccharide and chitosan well keep the antiviral and antibacterial properties and may serve as a promising multifunctional drug carrier for further biomedical applications.

Modified halloysite nanotubes decorated with Ceria for synergistic corrosion inhibition of Polyolefin based smart composite coatings

The deteriorating effect of corrosion can be controlled by applying suitable polymeric-based coatings. In this work, polyolefin based smart composite coatings containing modified halloysite nanotubes decorated with ceria particles were investigated to analyze their anti-corrosion behavior. For this purpose, halloysite nanotubes (Hals) were utilized as nanocarriers which were loaded with sodium dodecyl sulfate (SDS) as a corrosion inhibitor via overnight stirring and vacuum cycling method. The loaded Hals were then modified/decorated with cerium oxide (CeO2) particles by reacting cerium nitrate (Ce (NO3)3.6H2O) and sodium hydroxide (NaOH) which resulted in the formation of CeO2@HAL/SDS. The synthesized modified particles (CeO2@HAL/SDS) were characterized by energy-dispersive X-ray spectroscopy (EDX), Transmission electron microscopy (TEM), Fourier-Transform Infrared Spectrometer (FTIR), Thermogravimetric analysis (TGA), and differential thermal gravimetric analysis (DTA), X-ray diffraction analysis (XRD) and UV–vis spectroscopic analysis. TGA analysis results demonstrated that about 32% (w/w) of SDS has been loaded into Hal, and 47% (w/w) of CeO2 has been immobilized on the surface of Hal. UV–Vis analysis results demonstrated the pH-sensitive and time-dependent release behavior of synthesized particles. Furthermore, the modified CeO2@HAL/SDS particles (1 wt%) were reinforced into the polyolefin-based matrix, coated on a polished steel substrate and their electrochemical properties were investigated. The electrochemical impedance spectroscopy (EIS) analysis confirms the promising improvement in the corrosion inhibition performance of polyolefin coatings modified with CeO2@HAL/SDS particles when compared to the polyolefin composite coatings modified with HAL/SDS due to the synergistic corrosion inhibition performance of Ce(OH)3 and Fe-SDS formation at the cathodic and anodic region of steel.

Mussel-inspired grafting pH-responsive brushes onto halloysite nanotubes for controlled release of doxorubicin

The development of stimuli-responsive drug nanocarriers is an increasingly important area in nanomedicine because efficient delivery of toxic drugs to targeted tissues minimizes side effects. The specific objective of this study was to synthesize and characterize a novel pH-responsive drug carrier based on halloysite nanotubes for the controlled release of the anticancer drug doxorubicin. Poly(N,N-dimethylaminoethyl methacrylate) brushes were grafted from the surface of halloysite nanotubes using the combination of mussel-inspired polydopamine surface modification and activators regenerated by electron transfer in atom transfer radical polymerization. The chemical structure and morphology of the modified halloysite nanotubes were investigated by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, thermal gravimetric analysis as well as scanning and transmission electron microscopies. Dynamic light scattering and zeta potential analysis were carried out to evaluate the pH-responsivity of the functionalized halloysite nanotubes. The results of the drug loading and release study of pristine and functionalized halloysite nanotubes showed that grafting of poly(N,N-dimethylaminoethyl methacrylate) brushes on the polydopamine-modified halloysite nanotubes surface leads to a drastic increase in doxorubicin loading capacity and a highly pH-sensitive release behaviour. Less than 10 % of the loaded doxorubicin was released from poly (N,N-dimethylaminoethyl methacrylate)-grafted halloysite nanotubes at pH 7.4 after 24 h; in contrast, at pH 5.5 there was a continuous release of doxorubicin totalling 13 % in the first 30 min, i.e. lower than for the pristine halloysite nanotubes (32 %), but reaching 48 % after 24 h. Poly (N,N-dimethylaminoethyl methacrylate)-grafted halloysite nanotubes can hence be considered as a potential candidate for delivering highly toxic drug molecules to the acidic target sites.

Dual drug delivery system of teicoplanin and phenamil based on pH-sensitive silk fibroin/sodium alginate hydrogel scaffold for treating chronic bone infection.

For effective treatment of infected bone, it is essential to use local drug delivery systems with the ability to deliver both antibiotics and osteoinductive factors. Herein, a pH-sensitive silk fibroin (SF)/sodium alginate (SA) hydrogel scaffolds containing teicoplanin (TEC) and phenamil (PM) loaded SF nanoparticles (PMSFNPS) are introduced for treating chronic osteomyelitis. The TEC and PM showed a sustained- and pH-sensitive release behavior from SF/SA hydrogel. The higher release rate was seen in an alkaline pH in comparison to neutral and acidic pH during 10days. The eluted TEC maintained its antibacterial activity of >75% during 35days and in three different pH values (5.5, 7.4, and 8.5). The cellular study indicated that the scaffolds containing PMSFNPs could promote the cell viability, ALP activity, and matrix mineralization. Moreover, the in vivo effectiveness of hydrogel scaffolds were analyzed with radiography, histological and Immunohistochemistry evaluations. The lower infection and higher regeneration were observed in methicillin-resistant Staphylococcus aureus (MRSA) infected rat bone treated with hydrogel scaffold containing PMSFNPs and TEC compared to other groups. Consequently, this dual-drug delivery system could be a hopeful approach for effective treatment of chronic bone infection.

New ZnFe2O4@SiO2@graphene quantum dots as an effective nanocarrier for targeted DOX delivery and CT-DNA binder

The current study pronounces the synthesis and characterization of ZnFe2O4, ZnFe2O4@SiO2, graphene quantum dots (GQDs) and ZnFe2O4@SiO2@GQDs nanoparticles by different techniques such as VSM, XRD, IR, UV–Vis and SEM. For application in targeted drug delivery, then GQDs were immobilized on the surface ZnFe2O4@SiO2 via covalent linkage to surface amino groups.The competence of ZnFe2O4@SiO2@GQDs nanoparticles was assessed by loading and releasing of doxorubicin (DOX) as a standard anticancer drug at pH = 5 (pH of cancerous cell) and pH = 7.4 (pH of healthy cell). The attained results authenticate the pH sensitive release behavior of ZnFe2O4@SiO2@GQDs nanoparticles by releasing more DOX at cancerous pH (70%) than healthy pH (28%). To appraise the biological manner, ZnFe2O4@SiO2@GQDs nanoparticles were screened for their CT-DNA binding tendency by means of spectroscopic methods. The gained results of absorption spectroscopy and competitive fluorescence studies disclosed that nanoparticles bind to DNA through the intercalation mode and the loading of DOX on the nanocarrier has increased CT-DNA binding affinity up to 300 times. The cytotoxicity activity of ZnFe2O4@SiO2@GQDs and ZnFe2O4@SiO2@GQDs/DOX by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed on cancerous HeLa cell and healthy HEK-293 cell revealed that both nanoparticles exhibit concentration-dependent behavior on both cell lines, so that with increasing nanoparticle concentration, the cell viability percentage decreases, although nanocarriers containing DOX expression a more severe effect. Treatment of HeLa cells with 10 µg/mL of the ZnFe2O4@SiO2@GQDs/DOX nanoparticles showed that the nanoparticles induce cell death by apoptosis and cause detention of cell cycle in G2 phase. The results of the study expression the potential of the nanocarrier for targeted and controlled drug delivery, which should be given more attention and modified as a nanocarrier.

Synthesis of ZnFe2O4@SiO2 nanoparticles as a pH-sensitive drug release system and good nano carrier for CT-DNA binding

In the present research, the synthesis process of ZnFe2O4@SiO2 nanoparticles is expressed and its properties have been evaluated with XRD, SEM, EDS, VSM and FT-IR techniques. The decrease in saturation magnetization from 75.44 to 33.38 emug−1 is attributed to the formation of a silica layer around the ZnFe2O4 nanoparticles. The efficiency of ZnFe2O4@SiO2 nanoparticles as drug delivery carrier was evaluated by loading and releasing of doxorubicin as a model drug. The drug release results showed that the drug release amounts is higher at low pH, which means that the nanoparticles have a pH-sensitive release behavior. The in vitro interaction of ZnFe2O4@SiO2-DOX nanoparticles with calf thymus DNA (CT-DNA) was investigated by UV–Vis and fluorescence spectroscopy. Observation of the hypochromic effect (34%) in UV–Vis spectroscopy studies and data of competitive fluorescence assay with Hoechst 33258 and ethidium bromide probes confirms the intercalation binding mode between CT-DNA and ZnFe2O4@SiO2-DOX nanoparticles. Thermodynamic data recommend that the foremost forces involved in the interaction are of the electrostatic type. The obtained data show the importance of the nanoparticles as carriers for targeted and controlled drug delivery and DNA intercalator, so that better magnetic carriers can be designed using the nanoparticles.

Preparation and characterization of highly pH-sensitive biodegradable poly(ether-ester-urethane) and its potential application for drug delivery

The objective of this study is to offer a highly pH-sensitive biodegradable polyurethane for application as an intelligent drug delivery carrier. A new pyridinyl diol ((3-((2-(pyridin-4-yl)ethyl)thio) propane-1,2-diol, PyDH) was first synthesized via thiol-ene “click” reaction. Then, PyDH-based poly(ether-ester-urethane) (PEEU-Py) was designed and prepared through the condensation polymerization of PyDH diol, poly(ether-ester) diol and diisocyanate. The pendent pyridine groups and the polyester segments could endow the polymers with pH sensitivity and degradability, respectively. The bulk structures and physicochemical properties of PEEU-Py were characterized via1H NMR, FT-IR, GPC, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and tensile testing. The cast membranes exhibited a sharp transition of the equilibrium swelling ratio (ESR) at pH 8.5∼9.0, and ESR increases of more than twofold and eightfold at pH 1.5 relative to pH 7.4 and pH 12.0, respectively. In vitro drug release studies showed that the release efficiency from the membranes was increased with decreasing pH value. The pH-sensitive release behaviors were related mainly to the swelling ability, and the slow hydrolytic degradation rate of PEEU-Py membranes had minimal influence on it. In addition, the in vitro cytotoxicity was evaluated by an MTT assay with L929 fibroblasts, and a cell viability of more than 75 % indicated satisfactory cytocompatibility. All the results demonstrate the potential application of PEEU-Py as a biological on–off switch for drug carriers that is triggered by an external pH change.

Enhanced Penetrability of a Tetrahedral Framework Nucleic Acid by Modification with iRGD for DOX-Targeted Delivery to Triple-Negative Breast Cancer.

Poor penetrability and nonselective distribution of chemotherapeutic drugs are the main obstacles for chemotherapy for triple-negative breast cancer (TNBC). In our work, we developed a DNA-based drug delivery system to surmount these barriers. In addition, a tetrahedral framework nucleic acid (tFNA) was employed to load doxorubicin (DOX) with iRGD decoration to form a novel nanoparticle (tFNA/DOX@iRGD). The RGD sequence and the CendR motif in iRGD are used in tumor targeting and tissue penetration, respectively. Based on the sustained serum stability and pH-sensitive release behavior of DOX, tFNA/DOX@iRGD exhibited superiority for biomedical application. Moreover, tFNA/DOX@iRGD showed excellent deep penetration and drug accumulation in three-dimensional (3D) multicellular tumor spheroids compared to DOX and tFNA/DOX. Additionally, the therapeutic effect was verified in a 4T1 subcutaneous tumor model, and the complexes displayed a superior antitumor and antiangiogenic efficiency with fewer collateral damages. Therefore, these findings suggested that tFNA/DOX@iRGD might be a more effective pattern for drug delivery and TNBC therapy.

Oral Delivery of Gambogenic Acid by Functional Polydopamine Nanoparticles for Targeted Tumor Therapy

To enhance the water solubility, oral bioavailability, and tumor targeting of gambogenic acid (GNA), polydopamine nanoparticles (PDA NPs) were prepared to encapsulate and stabilize GNA surface modified by folic acid (FA) and then coated with sodium alginate (GNA@PDA-FA SA NPs) to achieve an antitumor effect by oral administration. GNA@PDA-FA SA NPs exhibited in vitro pH-sensitive release behavior. In vitro cell studies manifested that GNA@PDA-FA NPs had higher cytotoxicity to 4T1 cells compared with raw GNA (IC50 = 2.58 μM vs 7.57 μM). After being modified with FA, GNA@PDA-FA NPs were taken up easily by 4T1 cells. In vivo studies demonstrated that the area under the curve (AUC0→∞) of the plasma drug concentration-time of GNA@PDA-FA SA NPs was 2.97-fold higher than that of raw GNA, along with improving drug distribution in the liver, lung, and kidney tissues. In vivo anti-tumor experiments, GNA@PDA-FA SA NPs significantly inhibited the growth of breast tumors in the 4T1 xenograft breast cancer model via oral administration without obvious toxicity on major organs. Our studies indicated that the GNA@PDA-FA SA NPs modified with FA and coated with SA were a promising drug delivery system for targeting tumor therapy via oral administration.

Synthesis and drug delivery performance of gelatin-decorated magnetic graphene oxide nanoplatform

In the present study, we have designed and developed gelatin-decorated magnetic graphene oxide nanoplatform (MGO@GEL) for photothermal therapy and paclitaxel delivery. The surface morphology, chemical structure, magnetic property, and thermal stability of the MGO@GEL nanosheets were investigated using TEM, AFM, FTIR, XRD, BET, VSM, and TGA methods. Paclitaxel (PAC) as a chemotherapy drug, release behavior was performed at two pH levels and showed strong pH dependence. The anticancer efficiency and biocompatibility of the nanosheets were achieved by MTT analysis using MCF-7 cancer cells with and without 808 NIR laser and L-929 fibroblast cells. Furthermore, the pH-sensitive release behavior of the nanosheets demonstrated higher PAC release at pH 5.5 than at pH 7.4. Moreover, cytotoxicity analysis illustrated the MGO@GEL nanosheets are biocompatible while MGO@GEL@PAC nanosheets exhibited high toxicity to kill MCF-7 cells, especially with NIR laser. Based on the obtained results, the developed multifunctional nanostructures may be a promising candidate for chemo-photothermal therapy and drug delivery.

Glucosamine-conjugated graphene quantum dots as versatile and pH-sensitive nanocarriers for enhanced delivery of curcumin targeting to breast cancer

Applying multifunctional nanocarriers, comprising specifically traceable and tumor targeting moieties, has significantly increased in cancer theranostics. Herein, a novel targeted, trackable, and pH-responsive drug delivery system was fabricated based on glucosamine (GlcN) conjugated graphene quantum dots (GQDs) loaded by hydrophobic anticancer agent, curcumin (Cur), to evaluate its targeting and cytotoxicity potential against breast cancer cells with overexpression of GlcN receptors. The biocompatible photoluminescent GQDs were synthesized from graphene oxide through the green and facile oxidizing method. The structural and spectral characterizations of the as-prepared GQDs and Cur/GlcN-GQDs were investigated. The GQDs sizes were within 20–30 nm and showed less than ten layers. A pH-sensitive and sustained release behavior was also observed for the Cur loaded nanocarrier with a total release of 37% at pH 5.5 and 17% at pH 7.4 after 150 h. In vitro cellular uptake studies through fluorescence microscopy and flow cytometry exhibited stronger fluorescence for the targeted nanocarrier against MCF-7 cells compared to the non-targeted one, owing to higher cellular internalization via GlcN receptor-mediated endocytosis. Furthermore, the MTT assay results demonstrated the nontoxicity of the bare nanocarrier with the cell viability of above 94% even at concentrations as high as 50 μg·ml−1, while the Cur/GlcN-GQDs exhibited much more cytotoxicity against MCF-7 cells compared to Cur/GQDs. It is reasonable to conclude that this advanced multifunctional nano-assembly offers superior potential for breast cancer cell-targeted delivery.