Folic Acid Molecules Research Articles

Novel Difolate Targeting Nano-Level Ultrasound Contrast Agent for Therapy of Breast Cancer Tumor Cells

ABSTRACTA new type of difolate targeting nano-level ultrasound contrast agent ((folate molecule, FOL)2-TUAs) was prepared, so as to investigate its targeted binding effect with human breast cancer mammary carcinoma cells (MCF-7) in vitro. L-2-aminoadipic acid (L-2-AD) as a branch unit was inserted at the hydroxyl end of distearoyl phosphatidylethanolamine (DISP)-PEG2000-COOH to construct a tree structure. At this time, the free hydroxyl group in the distearoyl phosphatidylethanolamine (DISP)-PEG2000-COOH structure modified the FOL with the help of N-Hydroxysuccinimide/N,N'-dicyclohexylcarbodiimide (NHS/DCC). Each 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DISP-PEG2000) connected two FOLs to generate difolate targeted nanomaterials. Nano laser particle size (PS) and Zeta potential analyzer (ZPA) were applied to analyze the physical characteristics of the material such as PS and dispersion, and the enhanced development effect in vitro was detected by the ultrasonic diagnostic instrument. Besides, the targeted binding ability of the contrast agent based on this material to folate receptor (FR) overexpressing MCF-7 cells was analyzed by flow cytometry (FCM) and fluorescence microscope. In the experiment, hydrogen-1 nuclear magnetic resonance (1H NMR) demonstrated that (FOL)2-TUAs was successfully synthesized. The surface of this material was round and uniformly distributed without aggregation. According to the relative number of FOL molecules, non-targeted nano-agent (U-TUA), monofolate targeted nano-agent (FOL-TUA), and difolate targeted nano-agent ((FOL)2-TUA) were obtained. The in vitro imaging showed that different materials exhibited enhanced imaging effects in ultrasonic diagnostic equipment. FCM and fluorescence microscopy both indicated that the difolate TUA could achieve a good binding to MCF-7 cells. Most of the nano-agents were attached to the cell membrane, surrounded by red fluorophore, namely increasing the FOL content of DISP-PEG2000 chain could enhance the targeted binding ability of tumor cells.

Breast Cancer Targeting of a Drug Delivery System through Postsynthetic Modification of Curcumin@N3-bio-MOF-100 via Click Chemistry.

Metal-organic frameworks (MOFs) offer many opportunities for applications across biology and medicine. Their wide range of chemical composition makes toxicologically acceptable formulation possible, and their high level of functionality enables possible applications as delivery systems for therapeutics agents. Surface modifications have been used in drug delivery systems to minimize their interaction with the bulk, improving their specificity as targeted carriers. Herein, we discuss a strategy to achieve a tumor-targeting drug-loaded MOF using "click" chemistry to anchor functional folic acid (FA) molecules on the surface of N3-bio-MOF-100. Using curcumin (CCM) as an anticancer drug, we observed drug loading encapsulation efficiencies (DLEs) of 24.02 and 25.64% after soaking N3-bio-MOF-100 in CCM solutions for 1 day and 3 days, respectively. The success of postsynthetic modification of FA was confirmed by 1H NMR spectroscopy, Fourier transform infrared spectroscopy (FTIR), and liquid chromatography-mass spectrometry (LC-MS). The stimuli-responsive drug release studies demonstrated an increase of CCM released under acidic microenvironments. Moreover, the cell viability assay was performed on the 4T1 (breast cancer) cell line in the presence of CCM@N3-bio-MOF-100 and CCM@N3-bio-MOF-100/FA carriers to confirm its biological compatibility. In addition, a cellular uptake study was conducted to evaluate the targeting of tumor cells.

Ultradense Erythrocyte Bionic Layer Used to Capture Circulating Tumor Cells and Plasma-Assisted High-Purity Release.

The isolation and detection of rare circulating tumor cells (CTCs) from patient peripheral blood can help early diagnosis of cancer and evaluation of therapeutic outcomes. At present, most of the available strategies for enriching CTCs face serious problems with purity due to the nonspecific interactions between the capture medium and leukocytes. Inspired by the immune evasion ability of homologous red blood cells (RBCs), we modified the tumor-targeting molecule folic acid (FA) on the surface of RBCs by hydrophobic interactions. Under the treatment of polybrene, the charges on the surface of RBCs are neutralized, which reduces the mutual repulsion force. Furthermore, RBCs treated with polyethylene also have excellent deformability, thereby enabling engineered RBCs to form a dense bionic layer on the adhesive glass slide, which can greatly inhibit the nonspecific adhesion of leukocytes. The bionic layer can achieve high-purity enrichment of tumor cells in phosphate-buffered saline (PBS), and we can achieve high-activity release in plasma. The cell count showed over 80% capture efficiency and over 70% release rate, and the purity of CTCs obtained in the artificial blood sample after release was higher than 90%. The RBC bionic surface coating is notably cost-effective and highly applicable for CTC isolation in clinic practice, and thus provides new prospects for designing cell-material interfaces for advanced cell-based biomedical studies in the future.

A suicide diiron oxygenase in p ‐aminobenzoate biosynthesis in Chlamydia trachomatis

Folate is an essential cofactor required for several processes including DNA and amino acid biosynthesis. Folate molecules are made up of three parts: a pteridine ring, p-aminobenzoate (pABA), and a variable number of glutamate residues. Chlamydia trachomatis synthesizes folate de novo; however, several genes encoding enzymes required for the canonical folate biosynthesis pathway are missing, including PabA/B and PabC, which are normally required for pABA biosynthesis from chorismate. Previous studies have found that a single gene in C. trachomatis, CT610, functionally replaces the canonical pABA biosynthesis genes. Interestingly, CT610 does not use chorismate as a substrate. Instead, the CT610-route for pABA biosynthesis incorporates isotopically-labeled tyrosine into the synthesized pABA molecule. However, in vitro experiments revealed that CT610 produces pABA without any added substrates (including tyrosine) in the presence of a reducing agent and molecular oxygen. CT610 shares low sequence similarity to non-heme diiron oxygenases and the previously solved crystal structure revealed a diiron active site. Taken together, CT610 is proposed to be a self-sacrificing “suicide” enzyme that uses one of its active site tyrosine residues as a precursor to pABA in a reaction that requires O2 and a reduced diiron cofactor. Here, we discuss our recent progress towards uncovering the mechanism of CT610-catalyed pABA synthesis.

Encapsulating Single Atom Nanozyme in Extracellular Vesicles for Cancer Theranostics

Introduction Cancer is listed by the National Cancer Institute-National Institutes of Health (NIH NCI) in the US as a major disease which requires new therapeutic strategies to reduce its current high mortality. Glioblastoma (GBM) and pancreatic ductal adenocarcinoma (PDAC) are two highly aggressive cancer types originated from organs that are difficult to diagnose and trace in vivo. Experimental design To evaluate the feasibility of using single atom nanozyme (SAN) containing extracellular vesicles (EVs) to treat GBM and PDAC mouse models, we first mixed SAN particulates with HEK293T cells and collected cell-released exosomes in culture medium. We then purified SAN@EVs and added folic acid molecules on the surface of EVs to generate the tumor targeting function. The functionalized EVs were tested inn vitro for the photodynamic treatment of GBM and PDAC cell lines, and then in vivo using xenograft mouse models. Results We have demonstrated that electrical stimulation led to a short-term leakage of cell membrane for facilitated SAN uptake and increased EV production. Our preliminary data showed that many released EVs carry the payload of SAN. High quality SAN@EVs are enriched and purified using ultracentrifuge and sucrose gradient. After modifying the EV surface by folic acid-targeted monoclonal antibodies, SAN@EV-FA could be uptaken efficiently by cancer cells to greatly suppress the growth of cancer cells in vitro and could accumulate well in tumor and slow down tumor growth in vivo. Conclusions In animal biodistribution experiments, our results show that SAN@EV-FA particulates were mainly accumulated in the GBM and PDAC tumor. Moreover, the SAN@EV-FA particulates showed a good photodynamic therapeutic effect for the GBM and PDAC treatment. This novel theranostic nanoplatform has potential for cancer treatment in human in the future.

Building Block Symmetry Relegation Induces Mesopore and Abundant Open-Metal Sites in Metal–Organic Frameworks for Cancer Therapy

Building Block Symmetry Relegation Induces Mesopore and Abundant Open-Metal Sites in Metal–Organic Frameworks for Cancer Therapy

Folic acid-hydrophilic polymer coated mesoporous silica nanoparticles target doxorubicin delivery

Mesoporous silica nanoparticles (MSNs) gained significant attention, particularly in the pharmaceutical field. Folic acid (FA) shows marked promise as a targeting agent for its specific interaction with the folate receptor. This receptor is over-expressed on the cell surface of several cancerous cells like breast cancer. Polyethylene glycol (PE), as well as polypropylene glycol (PEG), is used to decorate nanoparticles to improve their biodistribution. Moreover, carboxymethyl beta-cyclodextrin (CM-β-CD), is used as a complexation molecule. In this study, we described the chemical synthesis, in vitro drug release and antiproliferative activity of doxorubicin-loaded/decorated MSNs further coupled with FA in two conditions: chemically bound or as a complex with CM-β-CD. Fourier Transform Infrared Spectroscopy with Transmission Electron Microscopy confirmed the successful surface change. Dynamic Light Scattering confirmed the change in surface characters like zeta potential, polydispersity index (PI), and size. PI improved from 0.58 to 0.23 while the size enlarged from 200 to 348 and 532 nm. Functionalized nanoparticles demonstrated more significant drug entrapment with (97%) while undecorated MSNs only showed (63%). Accordingly, we effectively synthesized FA-PEG2000-MSNs with IC50: 0.015 mg/mL targeting HeLa cells. This approach may allow potential applications as a drug delivery system in cancer chemotherapy. Highlights Mesoporous silica nanoparticles (MSNs) with a carboxylic acid or amine surface group can be successfully decorated with long-chain hydrophilic polymer via an amide bond. Carboxymethyl-β-cyclodextrin coupled with long-chain polymer as host to form a complex with targeting molecule folic acid. Folic acid can be anchored directly to a polymer coat. TEM; DLS and FTIR confirmed the surface modification. The drug encapsulation efficiency; cytotoxicity and selectivity of functionalized nanoparticles with PEG and conjugated with FA were the best. Chemical modification has improved cytotoxicity of doxorubicin and selectivity against Hela cells.

Loading harmine on nanographene changes the inhibitory effects of free harmine against MCF-7 and fibroblast cells

Today cancer is one of the main causes of death all over the world. Chemotherapy, which is one of the main therapies in the treatment of cancer, causes several side effects by damaging healthy cells. Therefore, carbon nanomaterial systems have been developed to optimize therapeutics procedures with the least negative consequences. Targeting nanographene oxide (NGO) with folic acid (FA) molecules allows the recognition of MCF-7 cells, which are folic acid receptor (FR) positive. Harmine is a pharmacologically active secondary metabolite that is produced by Peganum harmala. It is found that this metabolite induces apoptosis to human breast cancer cell lines by intercalating DNA molecules. In this study, harmine was loaded on FA-NGO (FA-NGO/harmine) via π–π stacking and hydrophobic interactions and the cytotoxicity against MCF-7, as FR positive cancerous cell, and fibroblast cells, as normal FR negative cell, were investigated. The in vitro studies illustrated that FA-NGO/harmine have remarkably higher cytotoxicity against MCF-7 cells, about 60% cell loss, in comparison with free harmine with 40% cell loss (in the concentration of 40 μg mL−1). However, the released amount of harmine into normal fibroblast cells was considerably low, only 28% cell loss in dose of 40 μg mL−1. Our results suggest that the controlled release of harmine into FR positive cancerous cells might have a substantially high cytotoxicity effect.

Highly sensitive folic acid colorimetric sensor enabled by free-standing molecularly imprinted photonic hydrogels

Folic acid is an important biological compound for human disease diagnosis. Traditional detection methods of folic acid are mostly time-consuming or dependent on analytical equipment. Here we demonstrate the rapid and colorimetric detection of folic acid using a novel colorimetric sensor enabled by molecularly imprinted photonic hydrogels, which are prepared by the polymerization of precursor solution in the interstitial voids of the polystyrene colloidal crystal and subsequent removal of colloidal crystal and folic acid molecules. As folic acid is instable under the preparation process of molecularly imprinted photonic hydrogels, we introduce folic acid (imprinted molecule) in the form of supramolecular complex with β-CD units to improve its stability and further create stable molecular recognition sites. The folic acid recognition can be directly transferred into a visually perceptible color change due to the highly ordered macroporous structure. With this novel sensory system, the highly selective, high sensitive (as low as 10–12 M), and rapid response (< 60 s) to folic acid is achieved without the use of instruments. A novel folic acid colorimetric sensor enabled by molecularly imprinted photonic hydrogels is successfully prepared.

High Hydrostatic Pressure Modulates the Folate and Ascorbic Acid Accumulation in Papaya (Carica papaya cv. Maradol) Fruit

High hydrostatic pressure (HHP) has previously induced de novo carotenoid (provitamin A) biosynthesis in papaya fruit tissue, possibly as a response to the oxidative stress. Papaya is also an excellent source of other vitamins, such as tetrahydrofolate (THF), its derivatives (folates, vitamin B9), and ascorbic acid (vitamin C). This work evaluated the immediate effects of HHP treatments (50–400 MPa for 3–60 min) on folate and ascorbic acid contents of fresh-cut papaya fruit. Folates and ascorbic acid were characterized by high-performance-liquid-chromatography with electrochemical and diode-array detections (HPLC-EC and DAD, respectively). Ascorbic acid levels increased in all conditions (4–28%) when compared with non-treated controls. 5-Methyl-THF (5-CH3-THF) (73%) and THF (22%) were the main folate species present in papaya fruit. HHP treatments increased 5-CH3-THF and total folate contents by 35% and 25%, at lower (50–100 MPa) and higher (400 MPa) pressures for 30 min, respectively. Folate molecule contains a glutamyl tail, involved in its function as a cofactor, tissue localization, and stability. 5-CH3-THF from papaya fruit exists with a very long polyglutamyl tail (Glu1–17). Both pressure and time increased concentrations of 5-CH3-THF Glu1 species (up to 250%), mainly at the 100 and 400 MPa/30 min conditions, whereas the polyglutamyl forms (Glu2–17) were not affected. Results documented, for the first time, that specific HHP treatments can positively modulate accumulation of vitamins B9 and C in papaya fruit.

Synthesis of Some New Folic Acid-Based Heterocycles of Anticipated Biological Activity

To date, no fused heterocycles have been formed on folic acid molecules; for this reason, and others, our target is to synthesize new derivatives of folic acid as isolated or fused systems. Folic acid 1 reacted with ethyl pyruvate, triethyl orthoformate, ethyl chloroformate, thioformic acid hydrazide, and aldehydes to give new derivatives of folic acid 2–6a,b. Moreover, It reacted with benzylidene malononitrile, acetylacetone, ninhydrin, ethyl acetoacetate, ethyl cyanoacetate, and ethyl chloroacetate to give the pteridine fused systems 10–15, respectively. Ethoxycarbonylamino derivate 5 reacted with some nucleophiles containing the NH2 group, such as aminoguanidinium hydrocarbonate, hydrazine hydrate, glycine, thioformic acid hydrazide, and sulfa drugs in different conditions to give the urea derivatives 16–20a,b. Compound 4 reacted with the same nucleophiles to give the methylidene amino derivatives 21–24a,b. The fused compound 10 reacted with thioglycolic acid carbon disulfide, malononitrile, and formamide to give the four cyclic fused systems 25–30, respectively. The biological activity of some synthesized showed moderate effect against bacteria, but no effect shown towards fungi.

Combined and selective miR-21 silencing and doxorubicin delivery in cancer cells using tailored DNA nanostructures

MicroRNAs play an important role in tumorigenesis and, among them, miR-21 is found to be aberrantly up-regulated in various tumors. The tumor-associated antigen, folate receptor alpha is a GPI-membrane protein overexpressed in many malignant tumors of epithelial origin, including ovarian and cervical cancers. Covalently bound octahedral DNA nanocages were functionalized with folate molecules and utilized as scaffolds to engineer four sequestering units with a miR-21 complementary sequence for obtaining biocompatible Fol-miR21-NC non-toxic nanostructures, to be able to selectively recognize folate receptor alpha-overexpressing cancer cells and sequester the oncogenic miR-21. qPCR assays showed that Fol-miR21-NCs reduce the miR-21 expression up to 80% in cancer cells in the first 2 days of treatment. Functional assays demonstrated that miR-21 sequestering leads to up-regulation of miR-21 tumor suppressor targets (i.e., PTEN and Pdcd4), reduction in cancer cell migration, reduction in proliferation, and increase in cell death. Fol-miR21-NCs can be efficiently loaded with the chemotherapeutic agent doxorubicin. Co-delivery of anti-miR-21 and doxorubicin showed additive cytotoxic effects on tumor cells, paving the way for their use as selective nucleic acid drugs.

Fluorescence Interaction Between Folate Molecules and CdTe and CdTe/CdS Quantum Dots

Fluorescence Interaction Between Folate Molecules and CdTe and CdTe/CdS Quantum Dots

Photothermal effect and cytotoxicity of CuS nanoflowers deposited over folic acid conjugated nanographene oxide.

Herein, we present the rational synthesis of a multimode photothermal agent, NGO-FA-CuS, for the advancement of photothermal therapy of cancer. The hierarchical architecture created in NGO-FA-CuS was attained by the covalent conjugation of folic acid (FA) to nanographene oxide (NGO) through amide bonding, followed by the hydrothermal deposition of CuS nanoflowers. In this approach, instead of mere mixing or deposition, FA was covalently bonded to NGO, which helped in retaining their intrinsic properties after binding and allowed to access them in the resulting hybrid nanostructure. In this specifically designed photothermal agent, NGO-FA-CuS, each component has an explicit task, i.e., NGO, FA and CuS act as the quencher, cancer cell-targeting moiety and photothermal transduction agent, respectively. Prior to the grafting of FA molecules and the deposition of CuS nanoflowers, sulfonic acid groups were introduced into NGO to provide stability under physiological conditions. Under irradiation using a 980 nm laser, NGO-FA-CuS was able to attain a temperature of 63.1 °C within 5 min, which is far beyond the survival temperature for cancer cells. Therefore, the resulting temperature recorded for NGO-FA-CuS was sufficient to induce hyperthermia in cancer cells to cause their death. When coming into contact with cancer cells, NGO-FA-CuS can cause a rapid increase in the temperature of their nucleus, destroy the genetic substances, and ultimately lead to exhaustive apoptosis under illumination using a near-infrared (NIR) laser. An excellent photothermal efficiency of 46.2% under illumination using a 980 nm laser and outstanding cytotoxicity against HeLa, SKOV3 and KB cells were attained with NGO-FA-CuS. Moreover, NGO-FA-CuS displays exceptional persistent photo-stability without photo-corrosiveness. The photothermal effect of NGO-FA-CuS was found to be dependent on its concentration and the power density of the laser source. It was found that its cytotoxicity toward cancer cells was enhanced with an increase in the concentration of NGO-FA-CuS and the incubation period.

Graphene oxide and its derivatives as promising In-vitro bio-imaging platforms

Intrinsic fluorescence and versatile optical properties of Graphene Oxide (GO) in visible and near-infrared range introduce this nanomaterial as a promising candidate for numerous clinical applications for early-diagnose of diseases. Despite recent progresses in the impact of major features of GO on the photoluminescence properties of GO, their modifications have not yet systematically understood. Here, to study the modification effects on the fluorescence behavior, poly ethylene glycol (PEG) polymer, metal nanoparticles (Au and Fe3O4) and folic acid (FA) molecules were used to functionalize the GO surface. The fluorescence performances in different environments (water, DMEM cell media and phosphate buffer with two different pH values) were assessed through fluorescence spectroscopy and fluorescent microscopy, while Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) and Scanning electron microscopy (SEM) were utilized to evaluate the modifications of chemical structures. The modification of GO with desired molecules improved the photoluminescence property. The synthesized platforms of GO-PEG, GO-PEG-Au, GO-PEG-Fe3O4 and GO-PEG-FA illustrated emissions in three main fluorescence regions (blue, green and red), suitable for tracing and bio-imaging purposes. Considering MTT results, these platforms potentially positioned themselves as non-invasive optical sensors for the diagnosis alternatives of traditional imaging agents.

Construction of biomimetic silver nanoparticles in the treatment of lymphoma

Lymphoma is a well-known malignant tumor in the human body. Although many anticancer drugs have been developed to improve the survival rate of patients, about 40% of patients continue to be recurrent or refractory, a key issue needing remedy. Therefore, it is necessary to identify alternative treatments to reduce the disease's mortality. To this effect, a new type of anti-lymphoma nanocomplex FA@RBCm-AgNPs was prepared using AgNPs as the core of nanoparticles along with the targeting molecule folic acid inserted erythrocyte membrane as the shell. The biomimetic properties of red blood cell membrane (RBCm) endow F-RAN with good biocompatibility as well as the ability to evade clearance of the reticuloendothelial system. In addition, F-RAN was modified with folic acid to actively and selectively identify tumor cells. In vivo and in vitro experiments demonstrate that F-RAN can inhibit lymphoma cells and induce apoptosis of stem cells while promoting apoptosis of lymphoma with no obvious side effects. Hence, F-RAN may serve as a new treatment for lymphoma.

Fabrication of Folic Acid-Decorated Hollow ZIF-8/Au/CuS Nanocomposites for Enhanced and Selective Anticancer Therapy.

Hollow nanomaterials have been used as an attractive platform for the integration of multiple bioactive components for effective anticancer therapy. Herein, we report a novel and facile strategy for the fabrication of hollow and monodispersed zeolitic imidazolate framework-8 (ZIF-8) by the self-template method with folic acid (FA) as a bioetcher. Gold nanocluster and folic acid were critical for the formation of the hollow ZIF-8 (thickness of 38 nm) during solvothermal synthesis. By integrating CuS nanoparticles (size of 4.9 nm), the resultant quadruple ZIF-8/Au/CuS/FA nanocomposites (denoted as FACZ) exhibited effective anticancer activities on FA receptor-positive MCF-7 and HepG-2 tumor cells but a weak killing effect on HCMEC/D3 cells. Folic acid molecules were conjugated to the external surface of FACZ, which simultaneously offered an excellent tumor-targeting ability and fluorescence imaging property. Although the photothermal therapy caused by CuS was not so obvious due to partial reduction, the nanosized FACZ after cellular uptake was able to release Cu(I) to enable chemodynamic therapy. This catalytically decomposed H2O2 to produce highly reactive oxygen species via the Fenton-like reaction as determined by the extracellular and intracellular hydroxyl radical. Our work offers a simple route for the fabrication of hollow ZIF-8 nanocomposite with active and selective anticancer activity. This is envisaged to have great potentials in biomedical applications.

Ultrasmall Ternary FePtMn Nanocrystals with Acidity-Triggered Dual-Ions Release and Hypoxia Relief for Multimodal Synergistic Chemodynamic/Photodynamic/Photothermal Cancer Therapy.

Multimodal imaging-guided synergistic anticancer strategies have attracted increasing attention for efficient diagnosis and therapy of cancer. Herein, a multifunctional nanotheranostic agent FePtMn-Ce6/FA (FPMCF NPs) is constructed by covalently anchoring photosensitizer chlorin e6 (Ce6) and targeting molecule folic acid (FA) on ultrasmall homogeneous ternary FePtMn nanocrystals. Response to tumor microenvironment (TME), FPMCF NPs can release Fe2+ to catalyze H2 O2 into •OH by Fenton reaction and simultaneously catalyze hydrogen peroxide (H2 O2 ) into O2 to overcome the tumor hypoxia barrier. Released O2 is further catalyzed into 1 O2 under 660 nm laser irradiation with Ce6. Thus, the FPMCF NPs exhibit superior dual-ROS oxidization capability including ferroptosis chemodynamic oxidization and 1 O2 -based photodynamic oxidization. Interestingly, FPMCF NPs reveal strong photothermal conversion efficiency exposed to an 808 nm laser, which can assist dual-ROS oxidization to suppress solid tumor remarkably. Additionally, Mn2+ can be released from FPMCF NPs to enhance longitudinal relaxivity (T1 -weighted magnetic resonance (MR) imaging) and Fe-synergistic transverse relaxivity (T2 -weighted MR imaging), which is convenient for diagnosis of solid tumors. Meanwhile, the fluorescent/photothermal (FL/PT) imaging function of FPMCF NPs can also accurately monitor tumor location. Therefore, FPMCF NPs with multimodal MR/FL/PT imaging-guided synergistic chemodynamic/photodynamic/photothermal cancer therapy capability have potential bioapplication in bionanomedicine field.

One-pot synthesis of folic acid modified carbonized polymer dots with red emittision for selective imaging of cancer cells

Carbonized polymer dots (CPDs), as a novel fluorescent material, have broad application prospects in the fields of bio-imaging, bio-sensors, disease diagnosis and photovoltaic devices due to their low cost, low toxicity, easy modification and little environmental impact. In this paper, folic acid (FA) modified CPDs (FA-CPDs) are synthesized from p-Phenylenediamine (p-PD) and FA molecules using a traditional one pot hydrothermal reaction in order to detect cancer cells containing a folate receptor (FR). The synthesized FA-CPDs were characterized by transmission electron microscopy, Fourier transfrom infrared spectroscopy, x-ray photoelectron spectroscopy, x-ray diffraction, UV–vis and fluorescence techniques. The red fluorescence emission is realized by doping phosphorus atoms into the carbonized polymer. Upon excitation at 513 nm, the maximum emission wavelength of FA-CPDs aqueous solution was obtained at 613 nm. Moreover, the as-prepared FA-CPDs exhibit excellent excitation-independent behavior and good stability with high quantum yield (QY) at about 30.6%. The binding of FA-CPDs with FRs on cancer cells produces target recognition and enters the cells through endocytosis. Additionally, it is worth noting that FA-CPDs have good biocompatibility and imaging in HeLa cells has been successfully achieved. Therefore, our FA-CPDs have potential applications as biocompatibility probes for cancer diagnosis and treatment.

A dual-targeting Fe3O4@C/ZnO-DOX-FA nanoplatform with pH-responsive drug release and synergetic chemo-photothermal antitumor in vitro and in vivo

Designing a proper intelligent platform to target cancer cells accurately and reducing its toxic side effects on normal tissues remain a challenge in medicine application. Herein, a novel dual-targeted and tumor microenvironment-triggered Fe3O4@carbon(C)/ZnO-doxorubicin (DOX) -folic acid (FA) drug delivery system with porous structure was designed and fabricated for the first time. The co-presence of Fe3O4 core and FA molecules functioned successfully could successfully realize the magnetic targeting and cancer cell-specific targeting. In addition, pH-responsive ZnO and porous carbon both derived directly from zinc-2-methylimidazolate complex (Zn-ZIF) could play the roles of "gatekeeper" and photothermal agent, respectively. The former could efficiently block the drug within mesoporous in blood environment for decreasing the damage to the normal tissues and achieving the controlled DOX release in the simulated and real acidic tumor microenvironment. And the latter could exhibit the intrinsic photothermal conversion efficiency upon 638nm laser irradiation. Therefore, the Fe3O4@C/ZnO-DOX-FA nanoplatform integrated dual targeting, controlled chemotherapy with photothermal therapy (PTT) for cancer, displaying a significantly superior synergistic anticancer efficiency both in vitro and in vivo experiments to either monotherapy. Above results suggested the prepared nanoplatforms might be a promising candidate for effectively synergetic therapeutics to cancers.