Amount Of DOX Research Articles

Thermo-responsive composite nanoparticles based on hydroxybutyl chitosan oligosaccharide: Fabrication, stimulus release and cancer therapy

Designing thermo-responsive nanocarriers based on biopolymers is fascinating and challenging for cancer therapy. In this study, thermo-responsive composite nanoparticles (CNPs) were prepared using hydroxybutyl chitosan oligosaccharide (HBCOS) and sodium caseinate (SC) via electrostatic interactions and covalent crosslinking. The temperature-responsive behaviors of CNPs were induced by the breakage of hydrogen bonds and the shrinkage of chains in nanoparticles. The CNPs exhibited concentration-independent thermo-responsive behavior, non-adsorption aggregation, and non-hemolysis, suggesting excellent stability and thermo-sensitivity. The initial release rate and final amount of DOX released from CNPs at 42 °C were higher than that at 37 °C, showing a thermo-responsive release, which was also more prominent at lower pH. The release of DOX from CNPs followed first order kinetics based on Fickian diffusion. In vitro cytotoxicity assays confirmed the thermo-responsive antitumor activity of DOX-loaded CNPs as the HT-29 cell viability incubated with DOX-loaded CNPs at 42 °C was significantly lower than that at 37 °C. Cellular uptake experiments proved that DOX-loaded CNPs accumulated in the cytoplasm after being endocytosed and promoted DOX release by increasing environment temperature. This study generated stable thermo-sensitive CNPs based on biopolymers, which can be used as potential nanocarriers for the controlled release of anticancer drugs for cancer therapy.

Construction of a MoS2@mSiO2 nanocarrier as a near-infrared/pH dual-responsive platform to control the drug release for anti-tumor

Designing new-type nanosystems to realize the combination of multiple treatment is an efficient routine to enhance the anti-tumor efficacy in clinic. In this study, molybdenum disulfide (MoS2) was selected as a photothermal agent, and mesoporous silica (mSiO2) was coated on the surface of MoS2 using the solvothermal and template removal methods. The chemotherapeutic drug doxorubicin hydrochloride (DOX) as a model drug was then loaded into the above MoS2@mSiO2 nanocarrier to prepare the tumor-targeting MoS2@mSiO2-DOX nanosystem. XRD, UV–Vis, FTIR, SEM, TEM, and DLS results jointly confirmed that the MoS2@mSiO2-DOX nanosystem with a particle size of approximately 370 nm was successfully synthesized. The XPS and BET analysis identified that the outer layer of MoS2@mSiO2 nanocarrier was SiO2, which has a large surface area of 99.41 m2/g with an average pore size of 3.5 nm coated on the MoS2. The in-vitro cytotoxicity and photothermal performance of the MoS2@mSiO2 nanodrug delivery system was tested, and the results show that MoS2@mSiO2 has a low toxicity to normal human liver cells (HL-7702), and which also exhibits a good photothermal stability with a photothermal conversion efficiency of 28.8%. With the aid of the large specific surface area of mSiO2 and the opposite zeta potential, a high amount of DOX was loaded on MoS2@mSiO2 nanocarrier, and the measured loading efficiency of DOX can reach up to 48.87%. The 48 h-drug release rate of MoS2@mSiO2-DOX reaches 35.65% under the conditions of near infrared (NIR) laser irradiation at pH=5.0, which is nearly 5 times higher than that of 6.26% under the normal physiological environment (pH=7.4 without NIR laser irradiation), indicating that the MoS2@mSiO2-DOX nanosystem possesses obvious pH and NIR laser responsive release characteristics. The MoS2@mSiO2 nanocarrier has good cytocompatibility, outstanding photothermal conversion and drug loading properties, and after DOX adsorption, the system exhibits excellent pH and laser responsive drug controlled release performance, which is expected to be widely used in the field of combining the photothermal-chemotherapy to synergistically resist tumor.

Spindle Monitor: A Tool for Real-Time Assessment and Concurrent Treatment of Postoperative Tumor Prognosis.

Cancer surgery remains a mainstay in clinical treatment. However, the efficacy of subsequent therapies largely depends on the precise evaluation of postoperative prognoses, underscoring the critical need for a comprehensive and accurate assessment of surgical outcomes. Nanoprobes targeting tumors offer a promising solution for visual prognostic assessment. In this study, we developed a "Spindle Monitor" system, designated as APPADs (Au NBPs@PDA-pep-AS1411-Dox), composed of core-shell nanoparticles. The core was made up of gold nanobipyramids (Au NBPs), coated with polydopamine (PDA), and subsequently loaded with peptide chains, AS1411, and doxorubicin (Dox). Upon deployment in the acidic tumor microenvironment (TME), APPADs released substantial amounts of Dox, initiating the apoptotic process. This triggered the activity of caspase-3, which is a crucial executor in the apoptotic pathway. Consequently, DEVD, a specific recognition site for caspase-3, was cleaved, enabling the disconnection of FITC-conjugated peptide chains and the recovery of fluorescence. Through assessing this fluorescence imaging effect, local laser irradiation could be precisely guided to the postoperative site, facilitating a synergistic combination of photothermal therapy and chemotherapy. Specifically, our "Spindle Monitor" APPADs had been validated to achieve accurate fluorescence imaging in vitro and in vivo, which demonstrated its potential value as a versatile tool for evaluating postoperative prognosis in surgical treatments, such as thyroid cancer, and assessing chemotherapy efficacy in difficult cases, like late-stage osteosarcoma. This promising tool lays a good foundation for development in visual prognosis evaluation after tumor surgery.

Redox-sensitive self-assembled micelles based on low molecular weight chitosan-lipoic acid conjugates for the delivery of doxorubicin: Effect of substitution degree of lipoic acid

Amphiphilic low molecular weight chitosan-lipoic acid (LC-LA) conjugates with different degrees of substitution (DS) of LA were synthesized by N, N′‑carbonyldiimidazole (CDI) catalysis to self-assemble into redox-sensitive micelles. Critical micelle concentration (CMC), size, zeta potential, biocompatibility and redox-sensitive behavior of blank micelles were investigated. The results indicated that blank micelles with low CMC, nanoscale size and positive zeta potential showed excellent biocompatibility and redox-sensitive behavior. Doxorubicin (Dox) loaded micelles were prepared by encapsulating Dox into blank micelles. The loading ability, trigger-release behavior, antitumor activity and cellular uptake of Dox loaded micelles were studied. The results demonstrated that Dox loaded micelles with superior loading ability exhibited redox-trigger behavior, strong antitumor activity and increased cellular uptake efficiency against A549 cell. Besides, the effect of DS of LA on above properties was estimated. An increase in DS of LA reduced the CMC and cumulative release amount of Dox, but improved the loading efficiency, antitumor activity, and cellular uptake of Dox loaded micelles, which resulted from stronger interaction of hydrophobic groups in micelles with the DS of LA increased. Overall, self-assembled LC-LA micelles with good biosecurity and redox-sensitive behavior hold promising application prospects in Dox delivery and improving cancer therapeutic effect of Dox.

Optimized silk fibroin nanoparticle functionalization with anti-CEA nanobody enhancing active targeting of colorectal cancer cells

This work aimed to establish a simple and feasible method to obtain silk fibroin nanoparticles (SFNPs) with uniform particles size, and then modify the SFNPs with nanobody (Nb) 11C12 targeting the proximal membrane end of carcinoembryonic antigen on the surface of colorectal cancer (CRC) cells. The regenerated silk fibroin (SF) was isolated using ultrafiltration tubes with a 50 kDa molecular weight cut-off, and the retention fraction (named as SF > 50 kDa) was further self-assembled into SFNPs by ethanol induction. Scanning electron microscope (SEM) and high-resolution transmission electron microscop showed that the SFNPs with uniform particles size were formed. Due to electrostatic adsorption and pH responsiveness, SFNPs have been proved to effectively load and release the anticancer drug doxorubicin hydrochloride (DOX) (DOX@SFNPs). Further, targeting molecule Nb 11C12 was used to modify these nanoparticles, constituting the targeted outer layer of the drug delivery system (DOX@SFNPs-11C12), achieving precise localization to cancer cells. The release amount of DOX observed from in vitro drug release profiles increased as follows: pH 7.4 < pH 6.8 < pH 5.4, demonstrating that the DOX release could be accelerated in a weakly acidic environment. In vitro cytotoxicity experiments displayed that SFNPs-11C12 nanoparticles exhibited good safety and biocompatibility. Drug-loaded nanoparticles, DOX@SFNPs-11C12, led to higher LoVo cells apoptosis compared to DOX@SFNPs. Fluorescence spectrophotometer characterization and confocal laser scanning microscopy further showed that the internalization of DOX was highest in the DOX@SFNPs-11C12, certifying that the introduced targeting molecule enhanced the uptake of drug delivery system by LoVo cells. This study provides a simple and operational approach to developing an optimized SFNPs drug delivery system modified by targeting Nb, which can be a good candidate for CRC therapy.

DOX-loaded hydroxyapatite nanoclusters for colorectal cancer (CRC) chemotherapy: Evaluation based on the cancer cells and organoids.

It is meaningful to find suitable in vitro models for preclinical toxicology and efficacy evaluation of nanodrugs and nanocarriers or drug screening and promoting clinical transformation of nanocarriers. The emergence and development of organoids technology provide a great possibility to achieve this goal. Herein, we constructed an in vitro 3D organoid model to study the inhibitory effect of nanocarriers on colorectal cancer. And designed hydroxyapatite nanoclusters (c-HAP) mediated by polydopamine (PDA) formed under alkaline conditions (pH 9.0), then used c-HAP to load DOX (c-HAP/DOX) as nanocarrier for improved chemotherapy. In vitro, drug release experiments show that c-HAP/DOX has suitable responsive to pH, can be triggered to the facile release of DOX in a slightly acidic environment (pH 6.0), and maintain specific stability in a neutral pH value (7.4) environment. c-HAP/DOX showed an excellent antitumor effect in the two-dimensional (2D) cell model and three-dimensional (3D) patient-derived colon cancer organoids (PDCCOs) model. In addition, c-HAP/DOX can release a sufficient amount of DOX to produce cytotoxicity in a slightly acidic environment, entering efficiently into the colorectal cancer cells caused endocytosis and induced apoptosis. Therefore, organoids can serve as an effective in vitro model to present the structure and function of colorectal cancer tissues and be used to evaluate the efficacy of nanocarriers for tumors.

Designed synthesis of prussian blue@Cu-doped zinc phosphate nanocomposites for chemo/chemodynamic/photothermal combined cancer therapy.

Designing a multifunctional nanoplatform that combines multiple treatments has emerged as an innovative cancer treatment strategy. A simple and clear route is put forward to develop Cu2+-doped zinc phosphate coated prussian blue nanoparticles (designated as PB@Cu2+/ZnP NPs) integrating tri-modal therapy (chemo, chemodynamic and photothermal therapy) for maximizing anti-tumor efficacy. The obtained PB@Cu2+/ZnP NPs possess drug loading capacity due to the mesoporous structure present in the Cu2+-doped ZnP shell. In addition, the Cu2+-doped ZnP shell can gradually degrade in response to the mildly acidic tumor microenvironment to release DOX and Cu2+, where the released drug plays the role of chemotherapy agent and the Cu2+ can react with intracellular glutathione to achieve a Cu-mediated Fenton-like reaction for chemodynamic therapy. Moreover, under laser irradiation, the heat garnered by the photothermal conversion of PB can be applied for photothermal therapy and enhance the generation of toxic ˙OH as well as the amount of DOX released, further boosting chemo- and chemodynamic therapy to realize a combined therapy. Importantly, the PB@Cu2+/ZnP NPs effectively limit the growth of tumors via the coordinated action of chemo/chemodynamic/photothermal therapy and no noticeable systematic toxicity can be found in mice. Taken together, the PB@Cu2+/ZnP NPs can act as a prospective therapeutic nanoplatform for multi-modal therapy of tumors.

Targeted delivery of doxorubicin and therapeutic FOXM1 aptamer to tumor cells using gold nanoparticles modified with AS1411 and ATP aptamers.

A targeted delivery platform was prepared to co-deliver both doxorubicin (Dox) as an anticancer drug and FOXM1 aptamer as a therapeutic substance to breast cancer cells (4T1 and MCF-7) to reduce Dox side effects and increase its therapeutic efficacy. The targeted system (AuNPs-AFPA) consisted of FOXM1 aptamer, AS1411 aptamer (targeting oligonucleotide), ATP aptamer, and gold nanoparticles (AuNPs) as a carrier. AuNPs were synthesized by reduction of HAuCl4. Next, after pegylation of ATP aptamer, FOXM1 aptamer-PEGylated ATP aptamer conjugate (FPA) was prepared. Then, the AS1411 aptamer and FPA were exposed to the AuNPs surface through their thiol groups. Subsequently, Dox was loaded into the complex to form a targeted therapeutic complex. The data of the MTT assay displayed that the targeted complex could remarkably reduce cell viability rate in target cells due to the overexpression of nucleolin on their cell membranes compared to nontarget cells, showing the targeting ability of AuNPs-AFPA-Dox. The in vivo antitumor effect confirmed that AuNPs-AFPA-Dox was capable of remarkably diminishing tumor growth relative to the free Dox in mice bearing 4T1 tumor cells. The results confirmed that the targeted system improved the therapeutic effect by loading high amounts of Dox alongside the presence of the therapeutic effect of FOXM1 aptamer. Finally, it can be concluded that AuNPs-AFPA-Dox by enhancing antitumor effectiveness and reducing toxicity toward non-target cells, can be used potentially as an effective strategy for the treatment of breast cancer.

Active and passive drug release by self-assembled lubricin (PRG4) anti-fouling coatings.

Electroactive polymers (EAPs) have been investigated as materials for use in a range of biomedical applications, ranging from cell culture, electrical stimulation of cultured cells as well as controlled delivery of growth factors and drugs. Despite their excellent drug delivery ability, EAPs are susceptible to biofouling thus they often require surface functionalisation with antifouling coatings to limit unwanted non-specific protein adsorption. Here we demonstrate the surface modification of para toluene sulfonate (pTS) doped polypyrrole with the glycoprotein lubricin (LUB) to produce a self-assembled coating that both prevents surface biofouling while also serving as a high-capacity reservoir for cationic drugs which can then be released passively via diffusion or actively via an applied electrical potential. We carried out our investigation in two parts where we initially assessed the antifouling and cationic drug delivery ability of LUB tethered on a gold surface using quartz crystal microbalance with dissipation monitoring (QCM) to monitor molecular interactions occurring on a gold sensor surface. After confirming the ability of tethered LUB nano brush layers on a gold surface, we introduced an electrochemically grown EAP layer to act as the immobilisation surface for LUB before subsequently introducing the cationic drug doxorubicin hydrochloride (DOX). The release of cationic drug was then investigated under passive and electrochemically stimulated conditions. High-performance liquid chromatography (HPLC) was then carried out to quantify the amount of DOX released. It was shown that the amount of DOX released from nano brush layers of LUB tethered on gold and EAP surfaces could be increased by up to 30% per minute by applying a positive electrochemically stimulating pulse at 0.8V for one minute. Using bovine serum albumin (BSA), we show that DOX loaded LUB tethered on para toluene sulfonic acid (pTS) doped polypyrrole retained antifouling ability of up to 75% when compared to unloaded tethered LUB. This work demonstrates the unique, novel ability of tethered LUB to actively participate in the delivery of cationic therapeutics on different substrate surfaces. This study could lead to the development of versatile multifunctional biomaterials for use in wide range of biomedical applications, such as dual drug delivery and lubricating coatings, dual drug delivery and antifouling coatings, cellular recording and stimulation.

Nano-gold micelles loaded Dox and Elacridar for reversing drug resistance of breast cancer.

The aim of this study was to provide a new effective carrier for rescuing the sensitivity of drug-resistant in breast cancer cells. Nano-gold micelles loaded with Dox and Elacridar (FP-ssD@A-E) were chemically synthesised. With the increase in the amount of Dox and Elacridar, the encapsulation rate of FP-ssD@A-E gradually increased, and the drug loading rate gradually decreased. FP-ss@A-E had a sustained-release effect. Dox, Elacridar, FP-ss@AuNPs, and FP-ssD@A-E significantly improved cell apoptosis, in which, FP-ssD@A-E was the most significant. FP-ssD@A-E significantly decreased the cell viability and improved the Dox uptake. The levels of VEGFR-1, P-gp, IL-6, and i-NOS were significantly decreased after Dox, Dox+Elacridar, FP-ss@AuNPs, and FP-ssD@A-E treatment. It was worth noting that FP-ssD@A-E had the most significant effects. The prepared FP-ssD@A-E micelles, which were spherical in shape, uniform in particle size distribution, and had good drug loading performance and encapsulation efficiency.

Ultrasenstive SERS biosensor based on Zn2+ from ZnO nanoparticle assisted DNA enzyme amplification for detection of miRNA

In this work, a simple and sensitive SERS biosensor was proposed for ultrasensitive detecting miRNA 122 based on ZnO nanoparticle amplification strategy and the full utilization of DNA chain. Firstly, ZnO@S1/S2 and CoFe2O4@S3 complexes can flock together with the assistance of target miRNA. Accompanied with the incremental amount of miRNA, the quantity of ZnO@S1/S2 would increase. Therefore, a significant amplification capability can be obtained by converting ZnO complexes into Zn2+ with the assistance of HCl. In this case, the DNA chain S2 can be obtained by the ZnO dissolving. In addition, through a clever design, the obtained Zn2+ can be further utilized to induce DNA enzyme cycle amplification to cleave S5 into DNA chain which was similar with DNA S2. This step greatly avoided the waste of DNA chains and improved the utilization efficiency of DNA chains. The S2 and abundant S2 analogues can complement with S4 on the Raman sensing interface to imbed lots of Raman probe DOX for obtaining strong Raman signal. By this way, with the increased number of miRNA, the S2 and abundant S2 analogues would increase, so the amount of DOX would increase to produce strong Raman signal to quantitatively detect target miRNA. As a result, this SERS biosensor based on Zn+ amplification and high utilization efficiency of DNA chain can obtain a low detection limit of 6.82 aM and wide linear range from 10 aM to 10 pM, which shown great potential in the clinical application and medical diagnosis.

Synthesis of ferroferric oxide@silicon dioxide/cobalt-based zeolitic imidazole frameworks for the removal of doxorubicin hydrochloride from wastewater

Due to its low-cost, eco-friendliness and easy mode of separation biosynthesized magnetic ferroferric oxide (Fe3O4) can be successfully used for the removal of organic contaminants from wastewater. However, there are some challenges that to date have limited this compound’s practical removal efficiency. Thus, in this study, a cobalt-based zeolitic imidazole frameworks (ZIF-67) coated biosynthesized ferroferric oxide@silicon dioxide (Fe3O4@SiO2) magnetic composite (Fe3O4@SiO2/ZIF-67) was prepared to address these issues and subsequently used to remove doxorubicin hydrochloride (DOX). Characterization results showed that the fabricated composite exhibited significant magnetic properties (16.1 emu·g−1) with a size ranging between 50 and 250 nm. The amount of DOX adsorbed by the composite (90.7 mg·g−1) was much higher than either of the component parts, which were only 35.7 and 82.5 mg·g−1 for Fe3O4@SiO2 and ZIF-67 respectively. This indicated enhanced DOX adsorption by Fe3O4@SiO2/ZIF-67. The DOX adsorption best fit a pseudo-second order kinetic and Langmuir adsorption model. These studies suggested that the DOX adsorption mechanism involved a combination of electrostatic interactions, π-π stacking, hydrogen bonding and pore filling. Regeneration and application studies, exposing Fe3O4@SiO2/ZIF-67 to real water samples, practically demonstrated that Fe3O4@SiO2/ZIF-67 with propensity for magnetic separation and recycle is a promising nanomaterial for DOX removal.

Controlling Doxorubicin Release from a Peptide Hydrogel through Fine-Tuning of Drug-Peptide Fiber Interactions.

Hydrogels are versatile materials that have emerged in the last few decades as promising candidates for a range of applications in the biomedical field, from tissue engineering and regenerative medicine to controlled drug delivery. In the drug delivery field, in particular, they have been the subject of significant interest for the spatially and temporally controlled delivery of anticancer drugs and therapeutics. Self-assembling peptide-based hydrogels, in particular, have recently come to the fore as potential candidate vehicles for the delivery of a range of drugs. In order to explore how drug–peptide interactions influence doxorubicin (Dox) release, five β-sheet-forming self-assembling peptides with different physicochemical properties were used for the purpose of this study, namely: FEFKFEFK (F8), FKFEFKFK (FK), FEFEFKFE (FE), FEFKFEFKK (F8K), and KFEFKFEFKK (KF8K) (F: phenylalanine; E: glutamic acid; K: lysine). First, Dox-loaded hydrogels were characterized to ensure that the incorporation of the drug did not significantly affect the hydrogel properties. Subsequently, Dox diffusion out of the hydrogels was investigated using UV absorbance. The amount of drug retained in F8/FE composite hydrogels was found to be directly proportional to the amount of charge carried by the peptide fibers. When cation−π interactions were used, the position and number of end-lysine were found to play a key role in the retention of Dox. In this case, the amount of Dox retained in F8/KF8K composite hydrogels was linked to the amount of end-lysine introduced, and an end-lysine/Dox interaction stoichiometry of 3/1 was obtained. For pure FE and KF8K hydrogels, the maximum amount of Dox retained was also found to be related to the overall concentration of the hydrogels and, therefore, to the overall fiber surface area available for interaction with the drug. For 14 mM hydrogel, ∼170–200 μM Dox could be retained after 24 h. This set of peptides also showed a broad range of susceptibilities to enzymatic degradation opening the prospect of being able to control also the rate of degradation of these hydrogels. Finally, the Dox released from the hydrogel was shown to be active and affect 3T3 mouse fibroblasts viability in vitro. Our study clearly shows the potential of this peptide design as a platform for the formulation of injectable or sprayable hydrogels for controlled drug delivery.

Invivo partial cellular reprogramming enhances liver plasticity and regeneration.

Mammals have limited regenerative capacity, whereas some vertebrates, like fish and salamanders, are able to regenerate their organs efficiently. The regeneration in these species depends on cell dedifferentiation followed by proliferation. We generate a mouse model that enables the inducible expression of the four Yamanaka factors (Oct-3/4, Sox2, Klf4, and c-Myc, or 4F) specifically in hepatocytes. Transient invivo 4F expression induces partial reprogramming of adult hepatocytes to a progenitor state and concomitantly increases cell proliferation. This is indicated by reduced expression of differentiated hepatic-lineage markers, an increase in markers of proliferation and chromatin modifiers, global changes in DNA accessibility, and an acquisition of liver stem and progenitor cell markers. Functionally, short-term expression of 4F enhances liver regenerative capacity through topoisomerase2-mediated partial reprogramming. Our results reveal that liver-specific 4F expression invivo induces cellular plasticity and counteracts liver failure, suggesting that partial reprogramming may represent an avenue for enhancing tissue regeneration.

Chitosan-coated poly (lactic-co-glycolide) nanoparticles for dual delivery of doxorubicin and naringin against MCF-7 cells

Present investigation examines the simultaneous encapsulation and delivery of DOX and NAR through PLGA-NPs and CS-coated PLGA-NPs to improve the efficacy and synergistic anticancer activity of DOX, and reduce its toxicity. Drug-loaded F3 and F4 were prepared by double-emulsion solvent-evaporation technique. PS, PDI, ZP and morphology of the NPs were determined using Zetasizer and SEM, respectively. %EE and %DL of both drugs were determined by indirect method. Dialysis tubing was used for in vitro release studies in phosphate buffer saline (pH 6.8) with SLS (0.1% w/v). Storage stability of the NPs was performed at 30 °C for 6-months. In vitro cytotoxicity was determined by MTT-assay, using MCF-7 cells. Cytotoxic effects of the NPs were also observed by visualizing the morphological changes in MCF-7 cells. PS, PDI and ZP of F4 were 366.8 ± 36.7 nm, 0.352 ± 0.033 and +35.57 ± 4.25 mV, respectively and those of F3 were 302.2 ± 45.4 nm, 0.283 ± 0.016 and −4.69 ± 2.66 mV. Increased PS and high positive ZP were found after CS-coating. Smooth-surfaced PLGA-NPs were observed by SEM, and slightly rough-surfaced NPs were found after CS-coating. %EE and %DL for DOX were 66.01%, 4.26% and 76.26%, 3.28% in F3 and F4, respectively. For NAR, these values were 77.82%, 3.22% and 71.85%, 4.64% in F3 and F4. The in vitro release profile revealed a sustained delivery of the drugs with 51% and 63% of DOX, as well as 80% and 78% of NAR at 48 h, from F3 and F4, respectively. Relatively high amounts of DOX and NAR were rapidly released from DOX-NAR-AqS at 2 h only. Release kinetic investigations justify the sustained release property of F3 and F4, and they followed the “Korsmeyer-Peppas model”. Release-exponent values suggest that the mechanism of the drug(s) release was Fickian-diffusion. Stability study revealed acceptable physicochemical changes for 6-months F4 showed the highest cytotoxicity (IC50, 1.52 μg/mL), when compared to F3, free DOX-NAR combination and DOX alone. Cytotoxicity and cell morphology represented the highest cellular uptake of F4. Conclusively, F4 could be an effective nano-carrier for DOX and NAR to improve their encapsulation, sustain their release, stability and simultaneous delivery against MCF-cells.

Temperature-induced unloading of liposomes bound to microgels

Bilayer lipid vesicles (liposomes) composed of zwitter-ionic (electroneutral) egg yolk lecithin and anionic phosphatidylserine were loaded with a water-soluble antitumor antibiotic Dox and electrostatically adsorbed onto the surface of thermo-sensitive microgels synthesized from 3-( N,N -dimethylamino)propylmethacrylamide, N,N -methylenebisacrylamide and 2,2′-azobis(2-methylpropionamidine) dihydrochloride. The resulting saturated microgel-liposomes complex with ultimately adsorbed 40 liposomes retains encapsulated drug in water solution at 25 °C. An increase in temperature induces a collapse of the microgel core and squeezing of the liposome shell, followed by liposome disruption and a release of encapsulated Dox. An intensive Dox leakage begins when temperature reaches 39 °C; a maximum amount of Dox is released within 5 min after starting the temperature trigger. The results are of importance for constricting of thermo-sensitive drug carries and developing protocols for the most productive drug release. • Anionic liposomes preserve their integrity after binding to cationic microgels. • Thermo-induced collapse of microgel core destroys the outer liposome layer. • Liposome disruption is accompanied by a fast release of encapsulated drug. • Sharp rise in the released drug was observed in between 39 and 41 °C. • Rigid latex particles bound to microgels form incompressible outer shell.

Laser-triggered combination therapy by iron sulfide-doxorubicin@functionalized nanozymes for breast cancer therapy

BackgroundThe use of magnetic nanozymes (NZs) with the ability to synchronize gas therapy through photodynamic and chemotherapy in the treatment of breast cancer has received much attention.ResultsHence, in this study, we designed a bovine lactoferrin-coated iron sulfide NZs containing doxorubicin (abbreviated as: FeS-Dox@bLf NZs) by wet-chemical synthesis method. Then, the physicochemical characteristics of synthesized NZs were explored by several methods. Also, the level of Fe2+, H2S and Dox releases from FeS-Dox@Lf NZs. Also, the cytotoxic effects of FeS-Dox@Lf NZs were investigated by cellular assays. After intravenous injections of NZs and laser irradiation, significant effects of FeS-Dox@Lf NZs on mice weight and tumor status were observed. Afterwards, not only the distribution of Dox in the body was examined by fluorescent, but also the time of Fe clearance and the amount of Dox and Fe retention in vital tissues were determined. The findings confirm that FeS-Dox@Lf NZs, in addition to targeted drug distribution in tumor tissue, resulted in superior therapeutic performance compared to free Dox due to reduced Dox side effects in vital tissues, and increased level of free radicals in 4T1 cells.ConclusionOverall, FeS-Dox@Lf NZs with the ability to synchronize chemotherapy and gas therapy raised hopes for more effective treatment of breast cancer.Graphic abstract

Highly sensitive determination of doxorubicin hydrochloride antitumor agent via a carbon nanotube/gold nanoparticle based nanocomposite biosensor

A glassy carbon electrode modified with multi-walled carbon nanotubes (MWCNTs) decorated with gold nanoparticles has been investigated for the first time as an ultrasensitive electrochemical sensor for the determination of doxorubicin hydrochloride (DOX), an efficient antitumor agent. The developed nanocomposite has been characterized by scanning electron microscopy (SEM), besides cyclic and linear sweep voltammetry electrochemical techniques. An efficient catalytic activity for the reduction of DOX has been demonstrated, leading to a significant increase in peak current density and a remarkable decrease in reduction over-potential. Under the optimal condition, a wide linear DOX concentration range from 1×10-11 to 1×10-6 M with a very low detection limit of 6.5 pM was achieved with the modified electrode. Meanwhile, the functionalized MWCNTs/gold nanoparticles indicated an appropriate selectivity, reproducibility, and repeatability as well as long-term stability. The promising outcomes of this research approved the applicability of the developed nanocomposite sensor towards trace amounts of DOX in pharmaceutical and clinical preparations.

Size-shrinkable and protein kinase Cα-recognizable nanoparticles for deep tumor penetration and cellular internalization

In the present study, the three functions, including enhanced permeability and retention (EPR) effect, deep penetration within tumor, and receptor-mediated endocytosis, were integrated into a single platform in order to improve antitumor efficiency. A novel nanoparticle (dendrigraft poly-L-lysine@glycyrrhetinic acid@cyclohexane dicarboxylic anhydride@doxorubicin@ hyaluronic acid composite) has been successfully developed and was denoted as DGL-GA-CDA-DOX-HA. The transmission electron microscope (TEM), dynamic light scattering (DLS), polymer dispersity index (PDI), fourier transform infrared spectrometer (FTIR), and zeta potentials were used to characterize the physicochemical properties of the nanoparticles. According to the results of TEM and DLS, the DGL-GA-CDA-DOX-HA nanoparticles could be rapidly degraded with a size shrink from 182.5 nm to 47.7 nm by hyaluronidase (HAase) added in the medium. The loading amount of DOX reached 252.03 ± 36.38 mg/g for DGL-GA-CDA-DOX nanoparticles. When the nanoparticles were in a medium with HAase at pH 5.0, the drug quickly released. However, when the nanoparticles were exposed to a medium without HAase at pH 5.0, or a neutral medium containing HAase, drug release slowed down. The modification of GA on nanoparticles significantly enhanced their affinity and cytotoxicity to hepatocellular carcinoma HepG2 cells. The study showed that the penetrability of DGL-GA-CDA-DOX and DGL-GA-CDA DOX-HA nanoparticles pre-degraded by HAase in vitro multicellular tumor spheroids were always better than that of DGL-GA-CDA-DOX-HA nanoparticles untreated by HAase. The imaging in vivo and ex vivo exhibited that DGL-GA-CDA-DOX-HA nanoparticles could preferentially accumulate in the tumor site. Correspondingly, the DGL-GA-CDA-DOX-HA displayed the preferable antitumor efficiency to other experimental groups in H22 tumor-bearing mice, with a tumor inhibition rate of 71.6%. In short, these results suggested that DGL-GA-CDA-DOX-HA nanoparticles could promote therapeutic effects by modulating particle size and GA receptor-mediated endocytosis.

Preparation and characterization of amphiphilic nanoparticles based on chondroitin sulfate A conjugated with hydrophobic drug for enhanced doxorubicin delivery

Novel chondroitin sulfate A conjugated doxorubicin (CSA-DOX) was synthesized and characterized. The mean diameter of CSA-DOX was 152 nm analyzed by dynamic light scattering (DLS). Further, DOX was physically encapsulated into the CSA-DOX nanoparticles. Total amounts of DOX in three kinds of DOX-loaded CSA-DOX (CSA-DOX/DOX) nanoparticles were from 21.8 to 24.2%. The mean diameters of three CSA-DOX/DOX nanoparticles were in the range of 167–177 nm. The shape of CSA-DOX/DOX nanoparticles was almost spherical. DOX released from DOX-loaded nanoparticles exhibited a biphasic way in phosphate buffered saline (PBS, pH 7.4). Cellular uptake studies exhibited that CSA-DOX and CSA-DOX/DOX nanoparticles could enhance the uptake of DOX into CD44 receptor-positive A549 cells. Moreover, the cytotoxicity of CSA-DOX/DOX nanoparticles against A549 cells significantly improved in contrast with free DOX and CSA-DOX nanoparticles. These results suggested that CSA-DOX copolymer could be a potential carrier for antitumor drug delivery.