Electrospun nanofibrous scaffolds as a platform to reduce melanoma tumour growth, recurrence, and promote post-resection wound repair.

Wound healing following skin tumour surgery still remains a major challenge. To address this issue, polysaccharide-loaded nanofibrous mats have been engineered as skin patches on the wound site to improve wound healing while simultaneously eliminating residual cancer cells which may cause cancer relapse. The marine derived polysaccharides kappa-carrageenan (KCG) and fucoidan (FUC) were blended with polydioxanone (PDX) nanofibers due to their inherent anti-cancer activity conferred by the sulphate groups as well as their immunomodulatory properties which can reduce inflammation resulting in accelerated wound healing. KCG and FUC were released sustainably from the blend nanofibers via the Korsmeyer-Peppas kinetics. MTT assays, live/dead staining and SEM images demonstrated the toxicity of KCG and FUC towards skin cancer MP 41 cells. In addition, MP 41 cells showed reduced metastatic potential when grown on KCG or FUC containing mats. Both KCG and FUC were non- cytotoxic to healthy L 929 fibroblast cells. In vivo studies on healthy Wistar rats confirmed the non-toxicity of the nanofibrous patches as well as their improved and scarless wound healing potential. In vivo studies on tumour xenograft model further showed a reduction of 7.15 % in tumour volume in only 4 days following application of the transdermal patch.

Short Antiangiogenic MMP-2 Peptide-Decorated Conjugated Linoleic Acid-Coated SPIONs for Targeted Paclitaxel Delivery in an A549 Cell Xenograft Mouse Tumor Model.

The design of targeted antiangiogenic nanovectors for the delivery of anticancer drugs presents a viable approach for effective management of nonsmall-cell lung carcinoma (NSCLC). Herein, we report on the fabrication of a targeted delivery nanosystem for paclitaxel (PTX) functionalized with a short antimatrix metalloproteinase 2 (MMP-2) CTT peptide for selective MMP-2 targeting and effective antitumor activity in NSCLC. The fabrication of the targeted nanosystem (CLA-coated PTX-SPIONs@CTT) involved coating of superparamagnetic iron-oxide nanoparticles (SPIONs) with conjugated linoleic acid (CLA) via chemisorption, onto which PTX was adsorbed, and subsequent surface functionalization with carboxylic acid groups for conjugation of the CTT peptide. CLA-coated PTX SPIONs@CTT had a mean particle size of 99.4 nm and a PTX loading efficiency of ∼98.5%. The nanosystem exhibited a site-specific in vitro PTX release and a marked antiproliferative action on lung adenocarcinoma cells. The CTT-functionalized nanosystem significantly inhibited MMP-2 secretion by almost 70% from endothelial cells, indicating specific anti-MMP-2 activity. Treatment of tumor-bearing mice with subcutaneous injection of the CTT-functionalized nanosystem resulted in 69.7% tumor inhibition rate, and the administration of the nanosystem subcutaneously prolonged the half-life of PTX and circulation time in vivo. As such, CLA-coated PTX-SPIONs@CTT presents with potential for application as a targeted nanomedicine in NSCLC management.

A Closed Loop Stimuli-Responsive Concanavalin A-Loaded Chitosan-Pluronic Hydrogel for Glucose-Responsive Delivery of Short-Acting Insulin Prototyped in RIN-5F Pancreatic Cells.

The optimal treatment of diabetes (in particular, type 1 diabetes-T1D) remains a challenge. Closed-loop systems (implants/inserts) provide significant advantages for glucose responsivity and providing real-time sustained release of rapid-acting insulin. Concanavalin A (ConA), a glucose affinity agent, has been used to design closed-loop insulin delivery systems but not without significant risk of leakage of ConA from the matrices and poor mechanical strength of the hydrogels impacting longevity and control of insulin release. Therefore, this work focused on employing a thermoresponsive co-forming matrix between Pluronic F-127 (PL) and structurally robust chitosan (CHT) via EDC/NHS coupling (i.e., covalent linkage of -NH2 from CHT and ConA to the -COOH of PL). The system was characterized for its chemical structure stability and integrity (FTIR, XRD and TGA), injectability, rheological parameters and hydrogel morphology (Texture Analysis, Elastosens TM Bio2 and SEM). The prepared hydrogels demonstrated shear-thinning for injectability with a maximum force of 4.9 ± 8.3 N in a 26G needle with sol-gel transitioning from 25 to 38 °C. The apparent yield stress value of the hydrogel was determined to be 67.47 Pa. The insulin loading efficiency within the hydrogel matrix was calculated to be 46.8%. Insulin release studies revealed glucose responsiveness in simulated glycemic media (4 and 10 mg/mL) over 7 days (97%) (305 nm via fluorescence spectrophotometry). The MTT studies were performed over 72 h on RIN-5F pancreatic cells with viability results >80%. Results revealed that the thermoresponsive hydrogel is a promising alternative to current closed-loop insulin delivery systems.

Surface Immobilization of Anti-VEGF Peptide on SPIONs for Antiangiogenic and Targeted Delivery of Paclitaxel in Non-Small-Cell Lung Carcinoma.

A design has been established for the surface decoration of superparamagnetic iron oxide nanoparticles (SPIONs) with anti-vascular endothelial growth factor peptide, HRH, to formulate a targeted paclitaxel (PTX) delivery nanosystem with notable tumor targetability and antiangiogenic activity. The design methodology included (i) tandem surface functionalization via coupling reactions, (ii) pertinent physicochemical characterization, (iii) in vitro assessment of drug release, anti-proliferative activity, and quantification of vascular endothelial growth factor A (VEGF-A) levels, and (iv) in vivo testing using a lung tumor xenograft mouse model. Formulated CLA-coated PTX-SPIONs@HRH depicted a size and surface charge of 108.5 ± 3.5 nm and -30.4 ± 2.3 mV, respectively, and a quasi-spherical shape relative to pristine SPIONs. Fourier transform infrared (FTIR) analysis and estimation of free carboxylic groups supported the preparation of the CLA-coated PTX-SPIONs@HRH. CLA-coated PTX-SPIONs@HRH exhibited high PTX loading efficiency (98.5%) and sustained release in vitro, with a marked dose dependent anti-proliferative activity in A549 lung adenocarcinoma cells, complimented by an enhanced cellular uptake. CLA-coated PTX-SPIONs@HRH significantly reduced secretion levels of VEGF-A in human dermal microvascular endothelial cells from 46.9 to 35.6 pg/mL compared to untreated control. A 76.6% tumor regression was recorded in a lung tumor xenograft mouse model following intervention with CLA-coated PTX-SPIONs@HRH, demonstrating tumor targetability and angiogenesis inhibition. CLA-coated PTX-SPIONs@HRH enhanced the half-life of PTX by almost 2-folds and demonstrated a prolonged PTX plasma circulation time from a subcutaneous injection (SC). Thus, it is suggested that CLA-coated PTX-SPIONs@HRH could provide a potential effective treatment modality for non-small-cell lung carcinoma as a nanomedicine.

Carboxymethyl cellulose/poloxamer gels enriched with essential oil and Ag nanoparticles: promising wound dressings.

Aim: Essential oils are promising antibacterial and wound-healing agents that should be explored for the design of wound dressings. Materials & methods: Topical gels prepared from a combination of carboxymethyl cellulose and poloxamer were incorporated with tea tree and lavender oil together with Ag nanoparticles. In vitro release, cytotoxicity, antibacterial, and wound healing studies were performed. Results: The gels displayed good spreadability with viscosity in the range of 210-1200 cP. The gels displayed promising antibacterial activity against selected Gram-positive and Gram-negative bacteria used in the study. The % cell viability of the gels was more than 90.83%. Conclusion: The topical gels displayed excellent wound closure in vitro revealing that they are potential wound dressings for bacteria-infected wounds.

What is this article about? This article reports the efficacy of carboxymethyl cellulose-based topical gels loaded with a combination of essential oils and silver nanoparticles as potential wound dressings for bacterial-infected wounds. What were the results? The topical gels induced a faster rate of closure than the untreated cells in 96 h. The gel formulations did not induce any significant cytotoxic effect. They were effective against Gram-negative and Gram-positive bacteria used in the study. What do the results of the study mean? The topical gels displayed promising healing effects in vitro revealing that they are potential wound dressings for treating bacteria-infected wounds.

In Vitro Prototyping of a Nano-Organogel for Thermo-Sonic Intra-Cervical Delivery of 5-Fluorouracil-Loaded Solid Lipid Nanoparticles for Cervical Cancer.

Solid lipid nanoparticles (SLNs) are used extensively to achieve site-specific drug delivery with improved bioavailability and reduced toxicity. This work focused on a new approach to provide site-specific stimuli-responsive delivery of SLNs loaded within thermo-sonic nano-organogel (TNO) variants to deliver the model chemotherapeutic agent 5-FU in treating cervical cancer. Pharmaceutically stable nanospherical SLNs comprising poly-L-lactic acid (PLA), palmitic acid (PA), and polyvinyl alcohol (PVA) were prepared and incorporated into TNO variants augmented by external thermal and ultrasound stimuli for release of 5-FU in the cervix. Results revealed that rate-modulated 5-FU release was achieved from SLNs (particle size =450.9 nm; PDI =0.541; zeta potential =-23.2 mV; %DL =33%) within an organogel upon exposure to either a single (thermo-) and/or both (thermo-sonic) stimuli. 5FU was released from all TNO variants with an initial burst on day 1 followed by sustained release over 14 days. TNO 1 provided desirable release over 15 days (44.29% vs. 67.13% under single (T) or combined (TU) stimuli, respectively). Release rates were primarily influenced by the SLN:TO ratio in tandem with biodegradation and hydrodynamic influx. Biodegradation by day 7 revealed that variant TNO 1 (1:5) released 5FU (46.8%) analogous to its initial mass than the other TNO variants (i.e., ratios of 2:5 and 3:5). FT-IR spectra revealed assimilation of the system components and corroborative with the DSC and XRD analysis (i.e., in ratios of PA:PLA 1:1 and 2:1). In conclusion, the TNO variants produced may be used as a potential stimuli-responsive platform for the site-specific delivery of chemotherapeutic agents such as 5-FU to treat cervical cancer.

Cellulose nanocrystals from Siam weed: Synthesis and physicochemical characterization.

The use of biomass for the development of environmentally friendly and industrially useful materials is still attracting global interest. Herein, cellulose nanocrystals were prepared from Siam weed. The production steps involved dewaxing the biomass sample, bleaching treatment, alkali treatment and acid hydrolysis. The resulting cellulose nanocrystals were characterized using Fourier transformed infrared (FTIR) spectroscopy, X-ray diffraction (XRD) spectroscopy, thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS) technique. Chemical composition results showed that Siam weed contained 39.6% cellulose, 27.5% hemicellulose, 28.7% lignin and 4.2% extractive. FTIR spectrum confirmed the presence of cellulose and absence of lignin and hemicellulose while XRD analysis revealed that the cellulose nanocrystals have crystallinity index of 66.2% and particle size of 2.2 nm. TGA revealed that thermal stability of raw Siam weed is lower than that of its cellulose nanocrystals due to the presence of the non-cellulosic component with lower temperature of degradation. SEM revealed that degradation of cellulosic chain had occurred. TEM confirmed that the crystal size is in the nanoscale with an average size <100 nm. DLS data revealed a nanocellulose with an average hydrodynamic size of 213 nm and a zeta potential at -9.57 mV.

Dual Rifampicin and Isoniazid Mannose-Decorated Lipopolysaccharide Nanospheres for Macrophage- Targeted Lung Delivery.

BACKGROUND: Currently, the treatment protocols for tuberculosis (TB) have several challenges, such as inconsistent oral bioavailability, dose-related adverse effects, and off-target drug toxicity. METHODS: This research reports the design and characterization of rifampicin (RIF) and isoniazid (INH) loaded hybrid lipid-polysaccharide nanoparticles using the solvent injection method, and demonstrated the influence of conjugated mannosyl residue on macrophage targeting and intracellular drug delivery capacity. RESULTS: The nanospheres, herein called mannose-decorated lipopolysaccharide nanoparticles, were spherical in shape, exhibiting average sizes less than 120 nm (PDI<0.20) and positive zeta potentials. Drug encapsulation was greater than 50% for rifampicin and 60% for isoniazid. The pH-responsive drug release was sustained over a 48-hour period and preferentially released more rifampicin/isoniazid in a simulated acidic phagolysosomal environment (pH 4.8) than in a simulated physiological medium. TGA and FTIR analysis confirmed successful mannose-grafting on nanoparticle surface and optimal degree of mannosylation was achieved within 48-hour mannose-lipopolysaccharide reaction time. The mannosylated nanoparticles were biocompatible and demonstrated a significant improvement towards uptake by RAW 264.7 cells, producing higher intracellular RIF/INH accumulation when compared to the unmannosylated nanocarriers. CONCLUSION: Overall, the experimental results suggested that mannose-decorated lipopolysaccharide nanosystems hold promise towards safe and efficacious macrophage-targeted delivery of anti-TB therapeutics.

Synthesis and Cytotoxic Activity of 1,2,4-Triazolo-Linked Bis-Indolyl Conjugates as Dual Inhibitors of Tankyrase and PI3K.

A series of new 1,2,4-triazolo-linked bis-indolyl conjugates (15a-r) were prepared by multistep synthesis and evaluated for their cytotoxic activity against various human cancer cell lines. It was observed that they were more susceptible to colon and breast cancer cells. Conjugates 15o (IC50 = 2.04 µM) and 15r (IC50 = 0.85 µM) illustrated promising cytotoxicity compared to 5-fluorouracil (5-FU, IC50 = 5.31 µM) against the HT-29 cell line. Interestingly, 15o and 15r induced cell cycle arrest at the G0/G1 phase and disrupted the mitochondrial membrane potential. Moreover, these conjugates led to apoptosis in HT-29 at 2 µM and 1 µM, respectively, and also enhanced the total ROS production as well as the mitochondrial-generated ROS. Immunofluorescence and Western blot assays revealed that these conjugates reduced the expression levels of the PI3K-P85, ß-catenin, TAB-182, ß-actin, AXIN-2, and NF-κB markers that are involved in the ß-catenin pathway of colorectal cancer. The results of the in silico docking studies of 15r and 15o further support their dual inhibitory behaviour against PI3K and tankyrase. Interestingly, the conjugates have adequate ADME-toxicity parameters based on the calculated results of the molecular dynamic simulations, as we found that these inhibitors (15r) influenced the conformational flexibility of the 4OA7 and 3L54 proteins.

Cell Secretome Strategies for Controlled Drug Delivery and Wound-Healing Applications.

There is significant interest in using stem cells in the management of cutaneous wounds. However, potential safety, efficacy, and cost problems associated with whole-cell transplantation hinder their clinical application. Secretome, a collective of mesenchymal stem-cell-stored paracrine factors, and immunomodulatory cytokines offer therapeutic potential as a cell-free therapy for the treatment of cutaneous wounds. This review explores the possibility of secretome as a treatment for cutaneous wounds and tissue regeneration. The review mainly focuses on in vitro and in vivo investigations that use biomaterials and secretome together to treat wounds, extend secretome retention, and control release to preserve their biological function. The approaches employed for the fabrication of biomaterials with condition media or extracellular vesicles are discussed to identify their future clinical application in wound treatment.

Recent patents on water-soluble polysaccharides for advanced drug delivery, tissue engineering and regenerative medicine.

Water-soluble polysaccharides have unique properties and have found wide application in the design of advanced drug-delivery systems and the biofabrication of tissue engineered scaffolds in regenerative medicine. This patent review provides a concise incursion into the mechanisms that define the key properties of water-soluble polysaccharides that have found embodiment within active patents recently granted (2020-2021). In addition, the relationship between their solubility and structural features such as molecular weight, ionic profile, degree of branching/crosslinking, side-chain flexibility and the presence/modification of functional groups that have been discusses. An assimilation of patents in which water-soluble polysaccharides are central to the design of therapeutic interventions applied to specialized treatments in oncology, infectious diseases and neuronal disorders is provided.

Synthesis of Novel Conjugated Linoleic Acid (CLA)-Coated Superparamagnetic Iron Oxide Nanoparticles (SPIONs) for the Delivery of Paclitaxel with Enhanced In Vitro Anti-Proliferative Activity on A549 Lung Cancer Cells.

The application of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) as a nanomedicine for Non-Small Cell Lung Carcinoma (NSCLC) can provide effective delivery of anticancer drugs with minimal side-effects. SPIONs have the flexibility to be modified to achieve enhanced oading of hydrophobic anticancer drugs such as paclitaxel (PTX). The purpose of this study was to synthesize novel trans-10, cis-12 conjugated linoleic acid (CLA)-coated SPIONs loaded with PTX to enhance the anti-proliferative activity of PTX. CLA-coated PTX-SPIONs with a particle size and zeta potential of 96.5 ± 0.6 nm and -27.3 ± 1.9 mV, respectively, were synthesized. The superparamagnetism of the CLA-coated PTX-SPIONs was confirmed, with saturation magnetization of 60 emu/g and 29 Oe coercivity. CLA-coated PTX-SPIONs had a drug loading efficiency of 98.5% and demonstrated sustained site-specific in vitro release of PTX over 24 h (i.e., 94% at pH 6.8 mimicking the tumor microenvironment). Enhanced anti-proliferative activity was also observed with the CLA-coated PTX-SPIONs against a lung adenocarcinoma (A549) cell line after 72 h, with a recorded cell viability of 17.1%. The CLA-coated PTX-SPIONs demonstrated enhanced suppression of A549 cell proliferation compared to pristine PTX, thus suggesting potential application of the nanomedicine as an effective site-specific delivery system for enhanced therapeutic activity in NSCLC therapy.

Current advances in cell therapeutics: a biomacromolecules application perspective.

INTRODUCTION: Many chronic diseases have evolved and to circumvent the limitations of using conventional drug therapies, smart cell encapsulating delivery systems have been explored to customize the treatment with alignment to disease longevity. Cell therapeutics has advanced in tandem with improvements in biomaterials that can suitably deliver therapeutic cells to achieve targeted therapy. Among the promising biomacromolecules for cell delivery are those that share bio-relevant architecture with the extracellular matrix and display extraordinary compatibility in the presence of therapeutic cells. Interestingly, many biomacromolecules that fulfil these tenets occur naturally and can form hydrogels. AREAS COVERED: This review provides a concise incursion into the paradigm shift to cell therapeutics using biomacromolecules. Advances in the design and use of biomacromolecules to assemble smart therapeutic cell carriers is discussed in light of their pivotal role in enhancing cell encapsulation and delivery. In addition, the principles that govern the application of cell therapeutics in diabetes, neuronal disorders, cancers and cardiovascular disease are outlined. EXPERT OPINION: Cell therapeutics promises to revolutionize the treatment of various secretory cell dysfunctions. Current and future advances in designing functional biomacromolecules will be critical to ensure that optimal delivery of therapeutic cells is achieved with desired biosafety and potency.

In Vitro and In Vivo Evaluation of a Cyclic LyP-1-Modified Nanosystem for Targeted Endostatin Delivery in a KYSE-30 Cell Xenograft Athymic Nude Mice Model.

This work investigated the use of LyP-1 as a homing peptide for p32 receptor targeting on the surface of an endostatin (ENT)-loaded chitosan-grafted nanosystem intended for intracellular delivery of ENT and mitochondrial targeting in a squamous cell carcinoma (SCC) cell line (KYSE-30) model. The angiogenic factors for VEGF-C and MMP2 were assessed with in vivo evaluation of the nanosystem upon ENT release and tumor necrosis in nude mice with a KYSE-30 cell xenograft. The LyP-1-modified nanosystem revealed a three-fold decrease in proliferation at 1000 µg/mL compared with the control and facilitated receptor-mediated cellular uptake and internalization. In addition, targeting of the Lyp-1-functionalized nanosystem to mitochondrial and nuclear proteins in vitro and in vivo was achieved. Up to 60% inhibition of KYSE-30 cell migration was observed and the expressions of VEGF-C and MMP-2 as angiogenic markers were reduced 3- and 2-fold, respectively. A marked reduction in tumor mass was recorded (43.25%) with the control, a 41.36% decrease with the nanoparticles and a 61.01% reduction with the LyP-1-modified nanosystem following treatment in mice. The LyP-1-functionalized nanosystem targeted tumor lymphatics, instigated nuclear rupture and mitochondrial distortion, and decreased cell proliferation and migration with inhibition of VEGF-C and MMP2 expression.

Novel ferrocenylbisphosphonate hybrid compounds: Synthesis, characterization and potent activity against cancer cell lines.

The toxicity of existing anticancer agents on healthy cells and the emergence of multidrug-resistance cancer cells have led to the search for less toxic anticancer agents with different mechanisms of action. In this study, a novel class of ferrocenylbisphosphonate hybrid compounds (H1-H8) were designed and characterized using NMR, IR and HRMS. The in vitro anticancer activity of the hybrid compounds on HeLa (cervix adenocarcinoma) and A549 (non-small cell lung cancer cell lines) was evaluated. The structure-activity relationship of the hybrid molecules was also studied. The lead compound, tetraethyl (3-(4-oxo-4-ferrocenylbutanamido) propane-1-1-diylbis(phosphonate) (H6) exhibited higher cytotoxicity on A549 (IC50 = 28.15 µM) than cisplatin (IC50 = 58.28 µM), while its activity on HeLa cells (IC50 = 14.69 µM) was equivalent to that of cisplatin 15.10 µM (HeLa cells). H6 (IC50 = 95.58 µM) was also five times less toxic than cisplatin (IC50 = 20.86 µM) on fibroblast NIH3T3 suggesting that H6 can be a future replacement for cisplatin due to its non-toxicity to healthy cells. Interestingly, some ferrocene and bisphosphonate parent compounds exhibited promising anticancer activity with 4-ferrocenyl-4-oxobutanoic acid (FI) exhibiting higher cytotoxic activity (IC50 = 1.73 µM) than paclitaxel (IC50 = 3.5 µM) on A549 cell lines. F1 also exhibited lower cytotoxicity than paclitaxel and cisplatin on the normal murine fibroblast cell line (NIH3T3). The molecular docking studies showed H6 strong binding affinity for the STAT3 signaling pathway in A549 cell line, and the MAdCAM-1 and cellular tumor antigen p53 proteins in HeLa cell lines.

A review on engineered magnetic nanoparticles in Non-Small-Cell lung carcinoma targeted therapy.

There are growing appeals forthe design of efficacious treatment options for non-small-cell lung carcinoma (NSCLC) as it accrues to ~ 85% cases of lung cancer. Although platinum-based doublet chemotherapy has been the main therapeutic intervention in NSCLC management, this leads to myriad of problems including intolerability to the doublet regimens and detrimental side effects due to high doses. A new approach is therefore needed and warrants the design of targeted drug delivery systems that can halt tumor proliferation and metastasis by targeting key molecules, while exhibiting minimal side effects and toxicity. This review aims to explore the rational design of magnetic nanoparticles for the development of tumor-targeting systems for NSCLC. In the review, we explore the anticancer merits of conjugated linoleic acid (CLA) and provide a concise incursion into its application for the invention of functionalized magnetic nanoparticles in the targeted treatment of NSCLC. Recent nanoparticle-based targeted chemotherapies for targeting angiogenesis biomarkers in NSCLC will also be reviewed to further highlight versatility of magnetic nanoparticles. These developments through molecular tuning at the nanoscale and supported by comprehensive pre-clinical studies could lead to the establishment of precise nanosystems for tumor-homing cancer therapy.

Folate-decorated, endostatin-loaded, nanoparticles for anti-proliferative chemotherapy in esophaegeal squamous cell carcinoma.

This study aims to design and synthesize Endostatin (ENT)-loaded nanoparticles using Folic acid (FA) as a driver for targeted anti-proliferative chemotherapy in Esophageal Squamous Cell Carcinoma (ESCC). An ionic gelation method was employed to formulate FA-decorated, ENT-loaded nanoparticles, which were tested in vitro on KYSE-30 cells using unbiased stereological approaches. FA-ENT nanoparticles were internalized into ESCC cells with preferential binging to the nucleus and mitochondria for necrotic and apoptotic effects. Nanoparticles showed increased proliferation inhibition of 64.71% and reduced KYSE-30 cell migration of up to 74.12% when compared to the control. Positively charged spherical nanoparticles, with selective pH responsive ENT release, were further tested in vivo employing a tumor xenograft model. Tumor mass increased up to 5505.54 mm3 in the control group while a substantial reduction occurred in the treatment group (native ENT, ENT-nano and FA-ENT-nano) down to 128.23 mm3 (97.67%). Tumor volume was reduced from 1000.2 mm3 to 567.64 mm3 (43.25%) in the native ENT group, from 324.43 mm3 to 190.25 mm3 (41.36%) in ENT-nano group (non-targeted system), and from 1374.21 mm3 to 998.67 mm3 (27.33%) in FA-ENT-nano group (targeted system) following treatment. There were no significant differences in the body weight of mice treated with the nano-formulations as opposed to the control mice. FA-decorated nanoparticles for active transport of ENT into tumor cells with an enhanced in vitro and in vivo anti-proliferative efficacy in ESCC therapy were synthesized.