Folic Acid Chitosan Research Articles

Harnessing nanotechnology for breast cancer management: UiO-66 (NH2) metal-organic frameworks functionalized with chitosan and folic acid for the efficient delivery of doxorubicin

Cancer is a leading cause of morbidity globally, which could be due to a lack of effective treatments. The inherent inadequacies of traditional medicines in terms of tumour selectivity and undesired toxicity urge us to seek alternative therapies to address these drawbacks. Metalorganic frameworks (MOFs) have been synthesized for use in drug delivery systems (DDS) because of their improved porosity and larger specific surface area. In this research, UiO-66-NH2 MOFs were synthesized via a solvothermal technique and functionalized with chitosan-folic acid (CS-FA) as a DDS for targeted doxorubicin (DOX) delivery. The MOF nanoplatforms were characterized via different techniques, including FTIR, PXRD, BET, TEM, DLS, TGA, SEM, and TGA. Remarkably, compared with the unmodified MOF, UiO-DOX@CS-FA delayed DOX release due to a gated effect induced by the CS-FA surface coating. pH-sensitive DOX release was observed, where 39.76 % of the drug was released in the tumour-mimicking pH of 5.2, whereas 5.84 % of the drug was released at physiological pH (7.4). In vitro cellular toxicity and uptake investigations demonstrated that UiO-DOX@CS-FA is a highly effective targeted DDS against MCF-7 breast cancer cells. Furthermore, in vivo toxicity studies in Wistar rats revealed no evidence of serious adverse effects. The variety of pharmacokinetic characteristics tested indicated that the bioavailability and release kinetics of DOX improved. Our findings lay the groundwork for the development and production of novel polymer conjugate-based nanoparticles with increased tumour-targeting efficacy.

Folate-chitosan Coated Quercetin Liposomes for Targeted Cancer Therapy.

Although quercetin exhibits promising anti-tumor properties, its clinical application is limited due to inherent defects and a lack of tumor targeting. This study aimed to prepare and characterize active targeting folate-chitosan modified quercetin liposomes (FA-CS-QUE-Lip), and its antitumor activity in vitro and in vivo was also studied. Box-Behnken Design (BBD) response surface method was used to select the optimal formulation of quercetin liposomes (QUE-LP). On this basis, FA-CS-QUE-LP was obtained by connecting folic acid chitosan complex (FA-CS) and QUE-LP. The release characteristics in vitro of QUE-LP and FA-CS-QUE-LP were studied. Its inhibitory effects on HepG2 cells were studied by the MTT method. The pharmacokinetics and pharmacodynamics in vivo were studied in healthy Wistar mice and S180 tumor-bearing mice, respectively. The average particle size, zeta potential and encapsulation efficiency of FA-CS-QUELP were 261.6 ± 8.5 nm, 22.3 ± 1.7 mV, and 98.63 ± 1.28 %, respectively. FA-CS-QUE-LP had a sustained release effect and conformed to the Maloid-Banakar release model (R2=0.9967). The results showed that FA-CS-QUE-LP had higher inhibition rates on HepG2 cells than QUE-Sol (P < 0.01). There was a significant difference in AUC, t1/2, CL and other pharmacokinetic parameters among QUE-LP, FA-CS-QUE-LP, and QUE-Sol (P < 0.05). In in vivo antitumor activity study, the weight inhibition rate and volume inhibition rate of FA-CS-QUE-LP were 30.26% and 37.35%, respectively. FA-CS-QUE-LP exhibited a significant inhibitory effect on HepG2 cells, influenced the pharmacokinetics of quercetin in mice, and demonstrated a certain inhibitory effect on S180 tumor-bearing mice, thus offering novel avenues for cancer treatment.

Bifunctional folic acid targeted biopolymer Ag@NMOF nanocomposite [{Zn2 (1,4-bdc) 2 (DABCO)} n] as a novel theranostic agent for molecular imaging of colon cancer by SERS

Without a doubt, cancer and its negative impact on human health have created many hurdles for people across the world since conventional approaches have not offered a reliable ability in the eradication of cancer. As a result, finding novel approaches, like using bimodal nanoparticles as a potential nanocarrier in molecular imaging and cancer therapy, is remarkably required these days. In the present study, ex-situ (Ge) and in-situ (Gi) green synthesized silver (Ag) nanoparticles entrapped in metal-organic framework nanocomposites (NMOF) coated with folic acid (FA) targeted chitosan (CS) was successfully developed as a novel bifunctional nanocarrier for detection and treatment of colon cancer cells. Then nanocarriers, such as NMOF–CS–FA, Ge–Ag@NMOF–CS–FA, Gi-Ag@NMOF–CS–FA, and C–Ag@NMOF–CS–FA, were characterized via FT-IR, DLS, SERS, TEM, and SEM and results have potentially confirmed the quality and quantity of synthesized nanocomposites. The hydrodynamic diameters of NMOF-CS, Ge–Ag@NMOF-CS, Gi-Ag@NMOF-CS, and C–Ag@NMOF-CS specimens were measured at around 99.7 ± 10 nm, 110 ± 10 nm, 118 ± 10 nm, 115 ± 10 nm, respectively. Also, the PDI values less than 0.2 confirm the reliable distribution of these nanocomposites. Afterward, the cell viability assay was conducted on HCT116 and HGF cell lines for evaluating biocompatibility and targeting efficiency of nanocomposites; FA functionalized nanocomposites have intensively indicated better performance in cancer cells targeting and their inhibition, and IC50 was attained for 10 ng/mL of Ge–Ag@NMOF–CS–FA while non-targeted nanocarriers did not have toxicity more than 20 % on HCT116 colon cancer cells. Moreover, according to the results, the cell viability of HGF normal cells was at least 85 % after being exposed to different concentrations of nanocomposites for 24 h. This indicates that the synthesized nanocomposites do not have significant toxic effects on normal cells. The results indicate that this novel nanocomposite has the potential to effectively deliver drugs to cancer cells.

Folate receptor-mediated delivery system based on chitosan coated polymeric nanoparticles for combination therapy of breast cancer

Combination therapy using two or more drugs with different mechanisms of action is an effective strategy for treating cancer. This is because of the synergistic effect of complementary drugs that enhances their effectiveness. However, this approach has some limitations, such as non-specific distribution of the drugs in the tumor and the occurrence of dose-dependent toxicity to healthy tissues. To overcome these issues, we have developed a folate receptor-mediated co-delivery system that improves the access of chemotherapy drugs to the tumor site. We prepared a nanoplatform by encapsulating paclitaxel (PTX) and curcumin (CUR) in poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) (PCL-PEG-PCL) co-polymer using a double emulsion method and coating nanoparticles with pH-responsive chitosan-folic acid (CS-FA) conjugate. The nanocarrier’s physicochemical properties were studied, confirming successful preparation with appropriate size and morphology. PTX and CUR could be released synchronously in a controlled and acid-facilitated manner. The dual drug-loaded nanocarrier exhibited excellent anti-tumor efficiency in MDA-MB-231 cells in vitro. The active targeting effect of FA concluded from the high inhibitory effect of dual drug-loaded nanocarrier on MDA-MB-231 cells, which have overexpressed folate receptors on their surface, compared to Human umbilical vein endothelial cells (HUVEC). Overall, the nanoengineered folate receptor-mediated co-delivery system provides great potential for safe and effective cancer therapy.

Folic acid-chitosan functionalized polymeric nanocarriers to treat colon cancer

In the present study, polymeric nanoparticles loaded with IRI and quercetin, a p-gp inhibitor, were developed to target folate receptors expressed by colon cancer cells for oral targeted delivery. This work reports the development of PNPs with an entrapment efficiency of 41.26 ± 0.56 % for IRI and 55.83 ± 4.51 for QT. PNPs were further surface modified using chitosan-folic acid conjugates for better targetability to obtain folic acid-chitosan coated nanoparticles. DLS and FeSEM revealed particles in the nanometric size range with spherical morphology, while FTIR and DSC provided details on their structure and encapsulation. In vitro drug release studies confirmed a sustained release pattern of IRI and QT, while cell line studies confirmed the superiority of C-FA-PNPs when tested on Caco2 cells. Pharmacodynamic studies in colon cancer induced rats showed similar efficacy for PNPs and C-FA-PNPs. Further examination from a bio-distribution study in healthy rats, revealed the failure of C-FA-PNPs to deliver the drugs to the colon adequately, while the PNPs improved the available concentration of IRI at the colon by almost 1.8 folds when compared to the available marketed product. Hence, the developed PNP formulation sticks out as a plausible substitute for the intravenous dosage forms of IRI which have been conventionally prevailing.

Surface-Decorated Nanocarrier as a Targeted Drug Delivery Cargo to Folate Receptor-Overexpressing Cells for Enhancing Anti-cancer and Anti-inflammatory Activity

Aims: Folate receptor (FR) is overexpressed in most cancer cells and activated macrophages entailed in rheumatoid arthritis (RA). The aim of the current study was the fabrication of FR-targeted nanocarrier loaded with methotrexate (MTX) to magnify its therapeutic efficacy and limit its toxicity.&#x0D; Methodology: Folic acid-chitosan (FA-CS) conjugate was synthesized and characterized. MTX loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were prepared, optimized and coated with different concentrations of FA-CS conjugate. The selected FA-CS coated MTX NPs formulation (F10) was evaluated via in vitro and in vivo studies.&#x0D; Results: F10 had satisfactory encapsulation efficiency (76.2%), homogenous particle size (278.6 nm) and positive zeta potential (34.0 mV) and displayed biphasic drug release pattern in different pH media. Further characterization of F10 cinched MTX incorporation in the polymeric matrix of the targeted nanocarrier. In vitro cytotoxicity assay to FR-positive and FR-negative cancer cells revealed the improved anticancer effect of F10 to FR-positive cancer cells, which was absent in FR-negative cells, compared to free MTX or uncoated MTX NPs (F2). F10 showed appropriate storage stability at refrigerated temperature up to 3 months. Moreover, oral administration of F10 in the treatment of complete Freund’s adjuvant (CFA)-induced RA in BALB/c mice conferred prodigious therapeutic outcomes and declined systemic toxicity compared to oral treatment with conventional pure MTX or commercial MTX tablets.&#x0D; Conclusion: The fabricated targeted nanocarrier could enhance the anticancer activity of MTX to FR-overexpressing cancer cells and could be a promising novel approach for oral administration of MTX in the treatment of RA or other inflammatory conditions associated with FR-overexpressing activated macrophages.

Lawsone encapsulated polylactic-co-glycolic acid nanoparticles modified with chitosan-folic acid successfully inhibited cell growth and triggered apoptosis in Panc-1 cancer cells.

The present research aims to encapsulate lawsone in polylactic-co-glycolic acid (PLGA) nanoparticles modified with folic acid (FA) and chitosan (CS) to study its anticancer effects against Panc-1 cells. The nanoparticles were analysed in means of shape/size and zeta potential index using scanning electron microscope and dynamic light scattering. High-performance liquid chromatography was applied to evaluate the lawsone entrapment efficacy. The authors performed acridine orange/propidium iodide staining and flow cytometry to monitor apoptosis induction and cell cycle arrest. The expressions of apoptosis-related genes (BAX and BCL-2) were assessed by real time PCR. Nanoparticle antioxidative and antibacterial activities were examined by DPPH/ABTS scavenging assay, disk diffusion method, and minimum inhibitory concentration and minimum bactericidal concentration evaluation. The NPs were 229.65nm, the encapsulation efficiency was 81%. The concentration of lawsone that exerts 50% cell growth inhibition (IC50 ) against Panc-1 cells was calculated 118.4μL. Apoptosis induction was evidenced by the increased number of orange cells and increased proportion of cells in G1-Sub phase respectively. Moreover, lawsone-loaded nanoparticle upregulated BAX gene expression, while downregulated BCL2expression, suggesting the activation of apoptotic pathway. The observed cytotoxic/apoptotic properties suggest that Lawson-loaded PLGA-FA-CS-NPs hold a great potential in pancreatic cancer treatment.

Folic Acid–Chitosan Oligosaccharide Conjugates Decorated Nanodiamond as Potential Carriers for the Oral Delivery of Doxorubicin

Oral administration of doxorubicin (DOX) is preferred but challenged owing to poor permeability in the gastrointestinal tract (GIT), efflux of P-glycoprotein, short residence time in the intestine, and rapid hydrolysis. Herein, folic acid-chitosan oligosaccharide conjugate (FA-COS)-modified hydroxylated nanodiamond (ND-OH) was designed to enhance the oral bioavailability of DOX. The carboxyl surface of ND was modified into hydroxyl terminal group to increase the colloidal stability of the system under different pH conditions in GIT. FA-COS modification could prolong retention time, endow the drug with sustained release properties, and actively target intestinal FA receptors. In contrast to DOX/ND-OH, the particle size of DOX/ND-OH/FA-COS increased from 189.5 ± 2.8 to 224.5 ± 1.4nm, and the zeta potential reversed from - 9.1 ± 0.2 to 14.8 ± 0.4mV. At 48h, DOX/ND-OH and DOX/ND-OH/FA-COS released 69.07 ± 5.70% and 35.87 ± 5.64%, respectively. FA-COS modification effectively enhanced the cytotoxicity and intracellular uptake of ND-OH/DOX by Caco-2 cells and prolonged intestinal retention in rats. The internalization of DOX/ND-OH and DOX/ND-OH/FA-COS was mainly mediated by energy-dependent clathrin- and caveolae-mediated endocytosis pathways. Pharmacokinetic study demonstrated that the AUC0-t of DOX/ND-OH and DOX/ND-OH/FA-COS was enhanced by 3.94- and 6.08-fold compared to DOX solution, respectively. These results illustrated that DOX/ND-OH/FA-COS could be an effective strategy to enhance the oral bioavailability of DOX.

Fabrication of biocompatible magnetic maltose/MIL-88 metal–organic frameworks decorated with folic acid-chitosan for targeted and pH-responsive controlled release of doxorubicin

Recently, metal–organic frameworks (MOFs) have attracted tremendous attention as promising porous drug delivery systems for cancer treatment. In this work, for the first time, a novel magnetic maltose disaccharide molecule modified with MIL-88 metal–organic framework (Fe3O4@C@MIL-88) was prepared, and then this targeted system was used for the delivery of the doxorubicin (DOX) drug. Eventually, Fe3O4@C@MIL-88-DOX were successfully decorated with folic acid conjugated chitosan (Fe3O4@C@MIL-88-DOX-FC) as a new targeted and controlled release drug system for treatment of MCF-7 breast cancer. The encapsulation efficiency of the DOX in the Fe3O4@C@MIL-88 was obtained at ∼83.6%. The in vitro drug release profiles showed a pH-responsive controlled release of DOX in acidic pH confirming the performance of the systems in the cancerous environment. The DOX release mechanism from systems at pH 5 also showed that the kinetic data well fitted to the Korsmeyer-Peppas and Fickian diffusion. Furthermore, in vitro cytotoxicity and DAPI staining study clearly illustrated that the synthesized Fe3O4@C@MIL-88 system had low cytotoxicity and good biocompatibility against MCF-7 cancer cells and MCF-10A normal cells. Whereas, Fe3O4@C@MIL-88-DOX and Fe3O4@C@MIL-88-DOX-FC exhibited good antitumor activity as a result of targeted delivery of DOX, which indicated the MCF-7 cell death with apoptotic effects. Based on these findings, the resulting carriers could be used as promising targeted drug delivery systems for cancer therapy.

Immunomodulation of MiRNA-223-based nanoplatform for targeted therapy in retinopathy of prematurity.

Retinopathy of prematurity (ROP) is characterized by pathological angiogenesis and associated inflammation in the retina and is the leading cause of childhood blindness. MiRNA-223 (miR-223) drives microglial polarization toward the anti-inflammatory phenotype and offers a therapeutic approach to suppress inflammation and consequently pathological neovascularization. However, miRNA-based therapy is hindered by the low stability and non-specific cell-targeting ability of delivery systems. In the present study, we developed folic acid-chitosan (FA-CS)-modified mesoporous silica nanoparticles (PMSN) loaded with miR-223 to regulate retinal microglial polarization. The FA-CS/PMSN/miR-223 nanoparticles exhibited high stability and loading efficiency, achieved targeted delivery, and successfully escaped from lysosomes. In cultured microglial cells, treatment with FA-CS/PMSN/miR-223 nanoparticles upregulated the anti-inflammatory gene YM1/2 and IL-4RA, and downregulated the proinflammatory genes iNOS, IL-1β, and IL-6. Notably, in a mouse oxygen-induced retinopathy model of ROP, intravitreally injected FA-CS/PMSN/miR-223 nanoparticles (1μg) decreased the retinal neovascular area by 52.6%. This protective effect was associated with the reduced and increased levels of pro-inflammatory (M1) and anti-inflammatory (M2) cytokines, respectively. Collectively, these findings demonstrate that FA-CS/PMSN/miR-223 nanoparticles provide an effective therapeutic strategy for the treatment of ROP by modulating the miR-223-mediated microglial polarization to the M2 phenotype.

Targeted delivery and anticancer effects of Chrysin-loaded chitosan-folic acid coated solid lipid nanoparticles in pancreatic malignant cells

The aim of this survey was to load Chrysin (CHY) on solid lipid nanoparticles (SLNs) and decorate the nanoparticles with folate-bound chitosan to increase the effectiveness of the treatment. CHY-SCF-NPs were synthesized by homogenizing and sonication methods and characterized. FA binding and encapsulation efficiency (HPLC), antioxidant capacity (ABTS and DPPH), cell viability assay (MTT), programmed cell death analysis (fluorescence staining, flow cytometry, and qPCR), and angiogenesis (CAM and molecular analysis) assay were done for assessment of therapeutic efficiency of CHY-SCF-NPs. Increases in size and change in surface charge of CHY-SLNs (PS: 84.3 nm and ZP: −18 mV) were reported after coating with folate-bound chitosan (PS: 125 nm and ZP: +34.9 mV). CHY-SCF-NPs inhibited PANC, MCF-7, A2780, and HepG2 as malignant cells and HFF as normal cells with IC50∼53, 55, 249, and >250 µg/mL, respectively. Also, CHY-SCF-NPs scavenged ABTS (IC50: 123.73 µg/mL), and DPPH (IC50: 108.7 µg/mL) free radicals and suppressed angiogenesis in the CAM and qPCR assays. Up-regulation of Bax and caspase 9 genes as well as the fluorescence staining and cell cycle results confirmed the pro-apoptotic properties of CHY-SCF-NPs. CHY-SCF-NPs can be considered a promising anti-cancer candidate for preclinical and clinical studies of pancreatic cancer.

Green synthesized-silver nanoparticles coated with targeted chitosan nanoparticles for smart drug delivery

The ever-increasing rate of people with colon cancer due to inappropriate diet and pollution in the industrial world leads to practical attempts by scientists to arrest it. In this work, we developed folic acid (FA) functionalized chitosan (CS) nanoparticles to co-delivery of imatinib (I) and silver (Ag) nanoparticles to HCT116 colon cancer cells. After efficient synthesis of FA–CS–Ag-I nanocomposite, various analytical devices including FT-IR, XRD, DLS, TEM, and SEM were used for qualification and quantification of the nanocomposite. Drug release study was demonstrated controlled release in normal pH (less than 20% after 24 h) and fast release in pH 5.0 (about 80% release after 24 h). In biomedical tests, MTT assay indicated excellent suppression against cancer cells, about 20% cell viability after 24 h of incubation with 20 nM concentration while it was over 70% cell viability for HFF1 cell at the same conditions. The BAX, Bcl2, BECLIN1, mTORC1 and ATG5 gene expression (for instance, a 5-fold and a 3-fold increase in expression of BAX and mTORC1 after incubation with 5 nM of FA–CS–Ag-I, respectively), apoptosis (65% and 42% apoptosis for Ag and FA–CS–Ag-I samples, respectively), and cell cycle arrest (24% and 12% cell cycle arrest for Ag and FA–CS–Ag-I samples, respectively) analyses have further confirmed the apoptosis-inducing ability of FA–CS–Ag-I and even Ag nanoparticles. These data have been depicted that FA–CS–Ag-I can potentially apply for active delivery of therapeutics against colon cancer.

Poly(lactic-co-glycolic acid)(PLGA)-based nanoparticles modified with chitosan-folic acid to delivery of Artemisia vulgaris L. essential oil to HT-29 cancer cells

In the present study, preparation of poly (lactic-co-glycolic acid)(PLGA) nanoparticles coated with chitosan (CS) conjugated to folic acid (FA) was applied to load Artemisia vulgaris L. essential oil (AVEO) and evaluate its anti-cancer effects. To do so, AVEO was encapsulated in PLGA-NPs by W/O method and the surface of nanoparticles was coated with CS attached to FA (AVEO-PCF-NPs). Then, the physicochemical properties of AVEO-PCF-NPs were evaluated by dynamic light scattering (DLS), Zeta potential, Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) methods, and subsequently, HPLC technique was used to calculate the amount of AVEO encapsulation and FA binding. MTT assay, florescent staining and cell cycle analysis were used to evaluate the occurrence of apoptosis. The chorioallantoic membrane (CAM) assay was done to evaluate the effect of AVEO-PCF-NPs on angiogenesis. AVEO-PCF-NPs suppressed cancer cells with IC50 ~78 μg/ml without inhibitory effect on normal cells. Arrest of cells in the SubG1 phase and AO/PI staining results showed the pro-apoptotic effects of AVEO-PCF-NPs. Significant reduction of blood vessel in samples treated with AVEO-PCF-NPs confirmed inhibitory effects of AVEO-PCF-NPs on angiogenesis. The effect of selective toxicity and the ability to induce apoptosis and inhibit angiogenesis introduces AVEO-PCF-NPs as a suitable candidate for cancer research.

Preparation and characterization of PLA-PEG/Chitosan-FA/DNA for gene transfer to MCF-7 cells

The ability of Chitosan-Folic acid and PLA-PEG polymers for gene delivery into MCF-7 cells was evaluated. The PLA-PEG copolymer is one of the most appealing nanoparticles for gene transfer to human cells because of its biocompatibility and high blood circulation. However, one of the barriers to the use of these polymers in gene therapy has always been the low effectiveness of these nanoparticles. In this study, Chitosan and folic acid were utilized to improve gene transfer efficiency and encapsulation of PLA-PEG/Chitosan-FA/DNA nanoparticles. PLA-PEG/Chitosan-FA/DNA nanoparticles with different concentrations of Chitosan-FA were prepared using double emulsion-solvent evaporation technique. The biological properties (i.e., biocompatibility, DNA release, and gene transfer ability to MCF-7 cells in vitro) as well as the physical and chemical properties (i.e., particle size, zeta potential, and the morphology of the resultant nanoparticles) of PLA-PEG/Chitosan-FA/DNA nanoparticles were investigated. The results showed that increasing the Chitosan-FA concentration in the PLA-PEG/Chitosan-FA/DNA nanoparticles resulted in an increase in zeta potential, DNA release, encapsulation, and gene delivery efficiency. The MTT assay showed PLA-PEG/Chitosan-FA/DNA nanoparticles exhibit low cytotoxicity and good compatibility. On the other hand, fluorescence microscopy and flow cytometry were used to test the ability of PLA-PEG/Chitosan-FA/DNA nanoparticles with varied concentrations of chitosan-folic acid to transfer the gene to MCF-7 cells. Flow cytometry and fluorescence microscopy analysis showed that increasing the concentration of chitosan-folic acid in PLA-PEG/Chitosan-FA/DNA nanoparticles improved gene transfer efficiency to MCF-7 cells.

5-Fluorouracil-Loaded Folic-Acid-Fabricated Chitosan Nanoparticles for Site-Targeted Drug Delivery Cargo.

Nanoparticles play a vital role in cancer treatment to deliver or direct the drug to the malignant cell, avoiding the attacking of normal cells. The aim of the study is to formulate folic-acid-modified chitosan nanoparticles for colon cancer. Chitosan was successfully conjugated with folic acid to produce a folic acid–chitosan conjugate. The folate-modified chitosan was loaded with 5-FU using the ionic gelation method. The prepared nanoparticles were characterized for size, zeta potential, surface morphology, drug contents, entrapment efficiency, loading efficiency, and in vitro release study. The cytotoxicity study of the formulated nanoparticles was also investigated. The conjugation of folic acid with chitosan was confirmed by FTIR and NMR spectroscopy. The obtained nanoparticles were monodispersed nanoparticles with a suitable average size and a positive surface charge. The size and zeta potential and PDI of the CS-5FU-NPs were 208 ± 15, 26 ± 2, and +20 ± 2, respectively, and those of the FA-CS-5FU-NPs were 235 ± 12 and +20 ± 2, respectively, which are in the acceptable ranges. The drug contents’ % yield and the %EE of folate-decorated NPs were 53 ± 1.8% and 59 ± 2%, respectively. The in vitro release of the FA-CS-5FU-NPs and CS-5FU-NPs was in the range of 10.08 ± 0.45 to 96.57 ± 0.09% and 6 ± 0.31 to 91.44 ± 0.21, respectively. The cytotoxicity of the nanoparticles was enhanced in the presence of folic acid. The presence of folic acid in nanoparticles shows much higher cytotoxicity as compared to simple chitosan nanoparticles. The folate-modified nanoparticles provide a potential way to enhance the targeting of tumor cells.

Synthesis and characterization of chitosan nanoparticles decorated with folate and loaded with dasatinib for targeting folate receptors in cancer cells

This study produced these Folate-Chitosan (FA-CS) conjugates by coupling a reaction with FA with CS, which resulted in better performance than previously attained due to the preservation of CS's basic chemical properties as well as the integration of the folate targeting receptor. The FA-CS conjugates were synthesised using tripolyphosphate (TPP), which is based on the chemical conjugation of the amino group of CS with the carboxylic group of FA and was validated using FTIR and 1H NMR spectroscopy, respectively. The FA-CS-NPs were shown to exhibit a unique core-shell structure under transmission electron microscopy; the encapsulation efficiency EE (percentage) and loading efficiency LE (percentage) of Dasatinib in FA-CS-DS-NPs were 50.7 ± 0.27% and 12.8 ± 0.21%, respectively. The FA-CS-DS-NPs exhibited a homogenous particle distribution of 103.17 ± 5.20 nm (PDI 0.081, zeta potential 20.2 ± 5.9 mV). As the pH of the dissolving solution lowers, the rate of DS release from the NPs increases, indicating that DS release from FA-CS-DS-NPs may be higher in a low pH environment than in a high pH environment. The MTT assay was used to examine the cell viability profile, which indicated that FA-CS-NPs did not induce significant cytotoxicity. In the cellular uptake study, for example, the intracellular concentration of DS in MCF-7 cells after exposure to FA-CS-DS-NPs was considerably higher than the concentration of DS in cells exposed to DS alone. As a result, FA-CS-DS-NPs show promise as a cancer therapeutic drug delivery mechanism. Graphical abstract representing the folate receptors targeting using folate decorated chitosan nps loaded with dasatinib.

Hybrid Theranostic Cubosomes for Efficient NIR-Induced Photodynamic Therapy.

In recent years, lipid bicontinuous cubic liquid-crystalline nanoparticles known as cubosomes have been under investigation because of their favorable properties as drug nanocarriers useful for anticancer treatments. Herein, we present organic/inorganic hybrid, theranostic cubosomes stabilized in water with a shell of alternate layers of chitosan, single strand DNA (model genetic material for potential gene therapy), and folic acid–chitosan conjugate (the outmost layer), coencapsulating up-converting Er3+ and Yb3+ codoped NaYF4 nanoparticles and daunorubicin. The latter acts as a chemotherapeutic drug of photosensitizing activity, while up-converting nanoparticles serve as energy harvester and diagnostic agent. Cellular uptake and NIR-induced photodynamic therapy were evaluated in vitro against human skin melanoma (MeWo) and ovarian (SKOV-3) cancer cells. Results evidenced the preferential uptake of the theranostic cubosomes in SKOV-3 cells in comparison to uptake in MeWo cells, and this effect was enhanced by the folic acid functionalization of the cubosomes surface. Nanocarriers coloaded with the hybrid fluorophores exhibited a superior NIR-induced photodynamic activity, also confirmed by the improved mitochondrial activity and the most affecting f-actin fibers of cytoskeleton. Similar results, but with higher photocytotoxicity, were detected when folic acid-functionalized cubosomes were incubated with SKOV-3 cells. Taken on the whole, these results prove these hybrid cubosomes are good candidates for the photodynamic treatment of tumor lesions.

Surface-modified CoFe2O4 nanoparticles using Folate-Chitosan for cytotoxicity Studies, hyperthermia applications and Positive/Negative contrast of MRI

Performance evaluation was conducted for hyperthermia and positive/negative contrast agents incorporating in-vivo angiography studies in Albino Wister rats using folate-chitosan (FC) coated cobalt ferrite (CF) nanoparticles. The structural characterizations were done using X-ray diffraction (XRD), Fourier transform infrared (FTIR), Raman and Mössbauer spectroscopy. The average particle size of CF nanoparticles was found to be 8 nm in transmission electron microscopy (TEM) images. The lattice fringe in the High-resolution transmission electron microscopy (HRTEM) and discrete circular ring in the selected area electron diffraction (SEAD) pattern confirmed the high degree of crystallinity with single phase inverse spinel structure of CF nanoparticles. The TEM images of folate chitosan coated cobalt ferrite (FCCF) demonstrated that the particles were highly dispersed. Electron energy loss spectroscopy (EELS) revealed no impurity phases and thermal analysis showed two transition temperatures around 284 °C and 614 °C, indicating the burning of folate and chitosan groups. The value of hydrodynamic diameter, polydispersity index (PDI), and zeta potential of FCCF nanoparticles were satisfactory at lower concentration (0.5 mg/ml, 1 mg/ml, 2 mg/ml). The self-heating properties of FCCF revealed that the temperature increases with the increase of concentration while specific loss power (SLP) decreases. The cytotoxic effect of FCCF in HeLa cell line confirmed the survival of HeLa cells up to 80–85% for the lower concentration. Magnetic Resonance Imaging (MRI) investigation on phantom using fast spin-echo (FSE) sequence revealed fast-relaxation of 0.02 s for 0.125 mg/ml concentration. Magnetic resonance angiography (MRA) conducted on Albino Wister rats presented higher efficacy of contrast agent for FCCF administered rats than the non-administered rats.

A multiple environment-sensitive prodrug nanomicelle strategy based on chitosan graftomer for enhanced tumor therapy of gambogic acid

A novel multiple environment-sensitive polymeric prodrug of gambogic acid (GA) based on chitosan graftomer was fabricated for cancer treatment. Folic acid–chitosan conjugates was complexed with thermosensitive amine terminated poly-N-isopropylacrylamide (NH2-PNIPAM) to develop FA-CSPN. Gambogic acid was conjugated with the graftomer via esterification to achieve high drug-loading capacity and controlled drug release. The resulting amphiphilic prodrug, O-(gambogic acid)-N-(folic acid)-N′-(NH2-PNIPAM) chitosan graftomer (GFCP), could self-assemble into micelles. As expected, the micelles were stable and biocompatible, featuring pH-, esterase- and temperature-dependent manner of drug release. Moreover, the anticancer effect studies of GFCP micelles were performed using a tumor-bearing mouse model and cellular assays (tumor cell uptake assay, cytotoxicity and tumor-sphere penetration). Collectively, GFCP micelles show both potential in vivo and in vitro in improving the anticancer effectiveness of GA owing to high loading capacity, targeted tumor accumulation, and multiple tumor microenvironmental responsiveness.

Design and development of folate-chitosan/CD nanogel: An efficient fluorescent platform for Cancer-specific delivery of AntimiR-21

Advances in the field of simultaneous diagnosis and treatment of cancer have introduced “nanotheranostic” systems that enable targeted co-delivery of imaging probes and therapeutic compounds. In this study, a simply designed fluorescent construction has been developed as a novel antimiR-21 nanocarrier for targeted imaging of SKOV3 cells. Fluorescent green carbon dots (CD) were synthesized from grapefruit extract through hydrothermal reaction. Folic acid-chitosan (FA-CS) conjugate was prepared according to the covalent chemistry for simultaneous loading of CD and antimiR-21 sequence in order to design FA-CS(CD/antimiR-21) nanoparticles. The FA-CS(CD/antimiR-21) nanoparticles showed uniform size distribution of 104.9 ± 30.68 nm. Nanoparticles with negligible toxicity and good serum stability transferred antimiR-21 sequence to cancer cells with 80–90% entrapment efficiency. In vitro cellular imaging and distribution studies were investigated by fluorescence microscopy that revealed higher cellular uptake of FA-CS(CD/antimiR-21) hybrid nanogel by SKOV3 ovarian cancer cells, which highly express folate receptors compared to fibroblast folate negative (FR−) (NIH3T3) cell lines. Ultimately, this investigation demonstrates that CD-loaded FA-CS nanogels provide a unique construction for cancer-specific fluorescent imaging capable of loading therapeutic agents.