Cancer Cells Overexpressing Folate Receptors Research Articles

Potential applications of Folate-conjugated Chitosan Nanoparticles for Targeted delivery of Anticancer drugs

Folate-conjugated chitosan nanoparticles represent a promising nanoplatform for targeted delivery of anticancer drugs. The nanoparticle carrier can protect the therapeutic agents from degradation and offer the ability to target cancer cells overexpressing folate receptors. This review summarizes recent research progress in synthesizing folate-conjugated chitosan nanoparticles as well as evaluating their potential as targeted drug delivery systems. The chemical conjugation of folic acid to chitosan is first discussed followed by an overview of different techniques for preparation of stable folate-conjugated chitosan nanoparticles less than 200 nm in size. Recent studies loading various anticancer drugs into these nanoparticles and investigating their in vitro cytotoxicity against multiple cancer cell lines are then summarized. The results indicate that folate-conjugated nanoparticles exhibit higher cytotoxicity and targeting efficiency compared to non-conjugated nanoparticles due to receptor-mediated endocytosis. Lastly, future challenges and opportunities are outlined including in vivo investigations to determine the effectiveness, toxicity, and pharmacokinetics of folate-conjugated chitosan nanoparticle systems as well as their potential clinical translation as targeted drug carriers for cancer chemotherapy.

Magnetic mesoporous silica nanoparticles mediated redox and pH dual-responsive target drug delivery for combined magnetothermal therapy and chemotherapy

A combination of multiple therapies is conducive to the treatment efficacy of cancer. Chemotherapy combined with magnetothermal therapy provides an outstanding synergy for cancer treatment. In this study, magnetic mesoporous silica nanoparticles (MMSN) were developed as a multipurpose nanoplatform for doxorubicin (DOX) delivery and magnetothermal treatment of cancer simultaneously. The MMSN were composed of Fe3O4 and mesoporous silica as core and shell. The folic acid (FA) linked chitosan (CS) was conjugated at the outlets of MMSN (MMSN-SS-FA) using disulfide bonds to avert the premature release of the drug in mesopores of MMSN, target folate receptor-overexpressed cancer cells and increase the safety and physiological stability of MMSN. The temperature of the MMSN suspension could be elevated from 37 °C to 45 °C at the concentration of 1 mg/mL under an alternating magnetic field (AMF), which exceeded the tumor ablating temperature. The in vitro drug release proved that the DOX/MMSN-SS-FA displayed the redox/pH/AMF multiple-responsive release. The cellular uptake results indicated that the MMSN-SS-FA could target folate receptor-overexpressed HeLa cells. The DOX/MSNS-SS-FA with AMF had the highest cytotoxicity at the equivalent drug concentration towards HeLa cells with a combination index (CI) of 0.276, demonstrating the synergistic treatment effect of chemotherapy and magnetic-thermal therapy. Meanwhile, the DOX/MMSN-SS-FA+AMF showed the strongest tumor inhibitory effect of 84 % on tumor growth. Therefore, the constructed MMSN-SS-FA with good biocompatibility and biosafety can act as multifunctional nano-platforms for tumor treatment.

One-pot preparation of biocompatible folate-functionalized graphitic carbon nitride quantum dots for targeted bioimaging

Graphitic carbon nitride quantum dots (CNQDs) have been widely used in bioimaging due to the unique structure and optical properties, but only a few works demonstrate targeted imaging. Herein, we report a universal one-pot strategy for preparation of targeting agent functionalized CNQDs by taking folate (FA) as an example through hot-fluid annealing of triazine tectons and derived FA. The FA-CNQDs with size of 3 ∼ 8 nm exhibit bright fluorescence, favorable colloidal stability, and well cytocompatibility and in vivo biocompatibility. The remarkable performance of FA-CNQDs in targeted imaging is demonstrated by incubation study with folate receptor overexpressed cancer cells and the cell derived multicellular spheroids. This convenient strategy would open a new avenue for synthesis of various functionalized CNQDs.

Detection of folic acid and imaging of folate receptor overexpressed cancer cells via a far-red silver nanoclusters with Baseline Resolved Between Excitation and Emission

In this work, we designed and synthesized a novel chemically stable fluorescent sensor of far-red emitting silver nanoclusters (PEI-AgNCs) by chemical reduction synthesis and ultrasonic resonance, in which polyethylenimine (PEI) was used as the synthetic template and 2-mercaptobenzothiazole (MBT) and sodium citrate (SC) were used as reducing agents. Due to the high electronegativity of benzothiazole, the antioxidant capacity of PEI-AgNCs was ensured. The PEI-AgNCs were found to be spherical with an average diameter of 2.1 nm, as observed by transmission electron microscopy (TEM). In addition, with a laser excitation of 348 nm, PEI-AgNCs showed the maximum emission intensity at 631 nm with a Stokes shift of 283 nm. Therefore, the use of the nanomaterial for bioimaging not only prevented the interference of biological background fluorescence, but also eliminated the crosstalk between excitation and emission light and the influence of light scattering on experimental results. Fluorescence titration experiment revealed that the fluorescence emission of PEI-AgNCs prepared in this work could be quenched by folic acid (FA) through electron transfer, and the FA in the range of 0.06–1.7 μM and 1.7–20 μM showed an excellent linear response with a detection limit of 12 nM (Sb/K = 3). Moreover, the test probe was successfully applied to the detection of FA in real samples with an average recovery of 98.6–102.3%. Finally, based on different expression levels of folate receptors (FRs) on the surface of different cells, HeLa cells were used as a model to evaluate the feasibility of FRs as fluorescent turn-on nanoprobes for tumor cell-targeted imaging. The results showed that the fluorescence intensity of HeLa cells was consistent with their FRs expression levels, demonstrating their potentiality for tumor cell-targeted imaging.

Folic acid-conjugated pH-responsive poly(methacrylic acid) nanospheres for targeted delivery of anticancer drugs to breast cancer cells

Folic acid (FA)-conjugated poly(methacrylic acid) nanospheres were synthesized as a pH-responsive nanocarrier for entrapping doxorubicin (DOX) to target folate-receptors-overexpressing breast cancer cells. To this end, poly(methacrylic acid) nanospheres were first prepared by precipitation polymerization, and then, the FA was conjugated to the pendent hydroxyl groups on the surface of nanospheres via the Stiglich esterification method. The chemical structure of the desired product was evaluated by Fourier transform infrared (FTIR) and hydrogen-nuclear magnetic resonance (1H NMR) techniques. The optimized product had a spherical shape with an average diameter of 149.2 nm and narrow particle size distribution (PDI = 0.268). Also, the surface charge of the prepared nanospheres was measured to be −41.3 mV, indicating a high colloidal stability in physiological media. The prepared nanocarrier displayed a good entrapment efficiency for DOX (86.5%), along with a high drug loading capacity (17.3%). The drug release experiments showed that, by decreasing the pH of the release medium from 7.4 to 5.5, the cumulative release of the DOX from the nanospheres increased from 22 to 32%, indicating the pH-responsivity of the prepared nanocarrier. Moreover, FA-conjugated poly(methacrylic acid) (FA-PMAA) nanospheres showed a higher anticancer efficacy against folate receptor-breast cancer cells (MCF-7 cancer cells) compared to the bare nanospheres and free DOX. The half-maximal inhibitory concentrations (IC50) of free DOX, PMAA, and FA-PMAA nanospheres were 12.8, 11.0, and 2.7 µg/mL, respectively. The obtained results suggest that the FA-PMAA nanospheres could be a promising pH-responsive nanocarrier for the targeted delivery of anticancer drugs to folate-receptor overexpressing cancer cells.

Evaluation of the Biological Activity of Folic Acid-Modified Paclitaxel-Loaded Gold Nanoparticles.

PurposeGold nanoparticles (AuNPs) with good physical and biological properties are often used in medicine, diagnostics, food, and similar industries. This paper explored an AuNPs drug delivery system that had good target selectivity for folate-receptor overexpressing cells to induce apoptosis.MethodsA novel drug delivery system, Au@MPA-PEG-FA-PTX, was developed carrying paclitaxel (PTX) on folic acid (FA) and polyethylene glycol (PEG)-modified AuNPs. The nanomaterial was characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and ultraviolet-visible spectroscopy (UV-Vis). Also, the biological activity of the AuNPs drug delivery system was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HL-7702, Hela, SMMC-7721, and HCT-116 cells. Furthermore, apoptotic activity using annexin V-FITC, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels was estimated by flow cytometry and fluorescence microscopy.ResultsAu@MPA-PEG-FA-PTX exhibited a distinct core-shell structure with a controllable size of 28±1 nm. Also, the AuNPs maintained good dispersion and spherical shape uniformity before and after modification. The MTT assay revealed good antitumor activity of the Au@MPA-PEG-FA-PTX against the Hela, SMMC-7721, and HCT-116 cells, while Au@MPA-PEG-FA-PTX produced better pharmacological effects than PTX in isolation. Further mechanistic investigation revealed that effective internalization of AuNPs by folate-receptor overexpressing cancer cells induced cell apoptosis through excessive production of intracellular ROS.ConclusionThe AuNPs drug delivery system showed good target selectivity for folate-receptor overexpressing cancer cells to induce target cell-specific apoptosis. These AuNPs may have great potential as theranostic agents such as in cancer.

Targeting Cancer Cells Overexpressing Folate Receptors with New Terpolymer-Based Nanocapsules: Toward a Novel Targeted DNA Delivery System for Cancer Therapy.

Chemotherapeutics represent the standard treatment for a wide range of cancers. However, these agents also affect healthy cells, thus leading to severe off-target effects. Given the non-selectivity of the commonly used drugs, any increase in the selective tumor tissue uptake would represent a significant improvement in cancer therapy. Recently, the use of gene therapy to completely remove the lesion and avoid the toxicity of chemotherapeutics has become a tendency in oncotherapy. Ideally, the genetic material must be safely transferred from the site of administration to the target cells, without involving healthy tissues. This can be achieved by encapsulating genes into non-viral carriers and modifying their surface with ligands with high selectivity and affinity for a relevant receptor on the target cells. Hence, in this work we evaluate the use of terpolymer-based nanocapsules for the targeted delivery of DNA toward cancer cells. The surface of the nanocapsules is decorated with folic acid to actively target the folate receptors overexpressed on a variety of cancer cells. The nanocapsules demonstrate a good ability of encapsulating and releasing DNA. Moreover, the presence of the targeting moieties on the surface of the nanocapsules favors cell uptake, opening up the possibility of more effective therapies.

CYTOTOXIC EVALUATION OF ANTICANCER FOLATE DECORATED CARBOPLATIN LOADED ALBUMIN NANOPARTICLES USING FOLATE RECEPTOR OVEREXPRESSING CELL LINES

Lack of selectivity, toxic side effects and multidrug resistance represent major limitations for chemotherapy treatment against cancer. The non-specific targeting of the chemotherapeutic agents leads to the rapid damage of normal cells. This could be significantly reduced through folate mediated nano-therapeutics which aimed to target cancerous cells. In this study, a folate decorated carboplatin loaded albumin nanoparticles was prepared aiming to successful active targeting of folate receptor overexpressing cancer cells which inconsequence decrease side effects and increase efficacy of carboplatin. The formulation was prepared using desolvation technique, glutaraldehyde as a cross linker, bovine serum albumin as a nanocarrier and folic acid as a targeting ligand. Physical characterization of the formulation was carried out as per of particle size, zeta potential and poly dispersity index (PDI). Results showed (267.29 nm) particles with (- 30.4 mV) potential and (0.069) PDI which confirmed a successful preparation of the formulation. For evaluation of the cytotoxic effect of the suggested formulation against the free form of the Carboplatin, an MTT cytotoxic assay was performed on folate receptor overexpressing cell lines (Caco2, PC3) a human colon cancer cell line and a prostate cancer cell line respectively. Results revealed higher significant efficacy represented by lower the half maximal Inhibitory concentration (IC50) values which gives a new hope for using carboplatin in a more effective and safe way in treatment after further clinical investigations.

Ru(II) Polypyridine Complex-Functionalized Mesoporous Silica Nanoparticles as Photosensitizers for Cancer Targeted Photodynamic Therapy

Cancer is the leading cause of death in the developed world. In the last few decades, photodynamic therapy (PDT) has augmented the number of medical techniques to treat this disease in the clinics. As the pharmacological active species to kill cancer cells are only generated upon light irradiation, PDT is associated with an intrinsic first level of selectivity. However, since PDT agents also accumulate in the surrounding, healthy tissue and since it is practically very challenging to only expose the tumor site to light, some side effects can be observed. Consequently, there is a need for a selective drug delivery system, which would give a second level of selectivity. In this work, a dual tumor targeting approach is presented based on mesoporous silica nanoparticles, which act by the enhanced permeability and retention effect, and the conjugation to folic acid, which acts as a targeting moiety for folate receptor-overexpressed cancer cells. The conjugates were found to be nontoxic in noncancerous human normal lung fibroblast cells while showing a phototoxic effect upon irradiation at 480 or 540 nm in the low nanomolar range in folate receptor overexpressing cancerous human ovarian carcinoma cells, demonstrating their potential for cancer targeted treatment.

Supramolecular imaging of spermine in cancer cells.

As an important biomarker, the overexpressed spermine has been widely investigated for cancer diagnosis and treatment. However, bioimaging of spermine in living cells is still a formidable challenge. Herein, we design a supramolecular imaging ensemble for spermine by the host-guest complexation of amphiphilic sulfonatocalix[5]arene (SC5A12C) assembly with lucigenin (LCG). Strong binding ability and complexation-induced fluorescence quenching properties enable SC5A12C to quench the fluorescence of LCG dramatically and to recover it completely due to the competition of overexpressed spermine in cancer cells. SC5A12C also exhibits excellent biocompatibility and promotes cellular uptake due to its ability to form ultra-stable assembly. Co-assembling folate further promotes the cellular uptake of folate receptor overexpressed cancer cells, contributing to enhanced bioimaging.

MgZnO Dual Gate Thin Film Transistor for the Sensitive Determination of Modified Folic Acid

Folate receptor (FR) is a typical tumor-associated antigen that has been widely used as a biomarker for the determination of cancer. A biosensing platform functionalized with folic acid (FA) is essential to FR detection because FA specifically binds FR. We demonstrate an MgZnO dual-gate thin-film transistor (MZO DGTFT) based biosensor for the sensitive determination of FA derivative, hexadecyl alkynated folic acid (HAFA). The receptor is an MZO nanostructure (MZO $_{\mathrm {nano}}$ ) modified sensing pad which electrically connects to the top gate of DGTFT. The bottom gate of DGTFT is used to bias the device to its optimum operation point, enabling high sensitivity. First, 11-azidoundecanoic acid (AA) was bond onto the MZO $_{\mathrm {nano}}$ surface as the linker layer, resulting in negative charges to MZO $_{\mathrm {nano}}$ due to carboxylic acid binding chemistry. HAFA was then immobilized on MZO $_{\mathrm {nano}}$ via click reaction with AA. HAFA is a polar molecule with the positive end adjacent to AA/MZO $_{\mathrm {nano}}$ , and therefore, the electrostatic condition of MZO $_{\mathrm {nano}}$ is impacted again. Such changes were detected by DGTFT that displayed significant drain current variations. Fourier-transform infrared spectroscopy (FTIR) imaging confirms such successful chemical processes. This MZO DGTFT biosensor with HAFA is promising for potential applications in the detection of FR overexpressed cancer cells.

Preparation and Characterization of Folate Decorated 5-Fluro Uracil Loaded Albumin Nanoparticles and In vitro Evaluation of its Cytotoxic Effect

In this study, a trial aims to decrease side effects and increase the efficacy of 5FU was established through active targeting of folate receptor overexpressing cancer cells using bovine serum albumin as a nanocarrier and folic acid as a targeting ligand. Physical characterization of size, potential, and polydispersity index (PDI) was performed, and (265.45 nm) particles with (- 31.1 mV) potential and (0.072) PDI were produced. For evaluation of the efficacy of the suggested formulation against the free form of the 5FU, a cytotoxic assay was performed on (Caco2, MCF7), a human colon cancer cell line, and a human breast cancer cell line, respectively, with different folate receptor-expressing features. MTT, NR & ATP assays were used, and all showed higher significant efficacy and a lower side effect of the formulation. Biochemical analysis of oxidative stress biomarker {Malonaldehyde (MDA)}, antioxidants biomarkers {Glutathione reductase (GR), Glutathione peroxidase (GPx)}, and a detoxifying enzyme {Glutathione transferase (GST)} was carried out along with quantitative real-time polymerase chain reaction (PCR) analysis of B cell lymphoma 2 (Bcl-2) gene. The results confirmed the cytotoxicity assay results. These results give new hope for using 5FU in a more effective and safe way in treatment.

An optimized mesoporous silica nanosphere-based carrier system with chemically removable Au nanoparticle caps for redox-stimulated and targeted drug delivery

To date, numerous drug delivery systems based on mesoporous silica nanoparticles (MSNs) have been explored, but little has been done on optimizing the structure and composition of MSNs to achieve effective drug delivery for cancer cells. Ideal mesoporous drug carriers should incorporate drugs in a way that prevents pre-release in biological surroundings before reaching the targeted area, which usually requires the capping of the open ends on the surface and the incorporation of targeting ligands on the exterior of nanocarriers. In this study, an MSN-based drug carrier system was synthesized with biocompatible Au nanoparticles (NPs) as the ‘hard caps’, and folic acid conjugated to the surface for targeting folate receptor-overexpressed cancer cells. Disulfide bonds linking Au and MSN NPs were introduced to the MSN surface as the redox-sensitive and chemically removable components. To study the effect of structures of MSNs in drug release, three types of MSNs were compared, including hollow mesoporous silica NPs, large-pore hollow mesoporous silica NPs and typical nano-sized pores on the surface (MSN). To achieve optimal coverage of thiol groups, two methods of functionalization were compared in effecting drug loading and release in vitro. Finally, the effect of residual surfactant was also discussed in anticancer studies. Therefore, the appropriate MSN nanostructure for redox-sensitive and targeted drug delivery was optimized.

Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds Against Different Cancer Cell Lines.

The synthesis, characterization and cytotoxic activity against different cancer cell lines of various mesoporous silica-based materials containing folate targeting moieties and a cytotoxic fragment based on a triphenyltin(IV) derivative have been studied. Two different mesoporous nanostructured silica systems have been used: firstly, micronic silica particles of the MSU-2 type and, secondly, mesoporous silica nanoparticles (MSNs) of about 80 nm. Both series of materials have been characterized by different methods, such as powder X-ray diffraction, X-ray fluorescence, absorption spectroscopy and microscopy. In addition, these systems have been tested against four different cancer cell lines, namely, OVCAR-3, DLD-1, A2780 and A431, in order to observe if the size of the silica-based systems and the quantity of incorporated folic acid influence their cytotoxic action. The results show that the materials are more active when the quantity of folic acid is higher, especially in those cells that overexpress folate receptors such as OVCAR-3 and DLD-1. In addition, the study of the potential modulation of the soluble folate receptor alpha (FOLR1) by treatment with the synthesized materials has been carried out using OVCAR-3, DLD-1, A2780 and A431 tumour cell lines. The results show that a relatively high concentration of folic acid functionalization of the nanostructured silica together with the incorporation of the cytotoxic tin fragment leads to an increase in the quantity of the soluble FOLR1 secreted by the tumour cells. In addition, the studies reported here show that this increase of the soluble FOLR1 occurs presumably by cutting the glycosyl-phosphatidylinositol anchor of membrane FR-α and by the release of intracellular FR-α. This study validates the potential use of a combination of mesoporous silica materials co-functionalized with folate targeting molecules and an organotin(IV) drug as a strategy for the therapeutic treatment of several cancer cells overexpressing folate receptors.

Insights into Nano-Photo-Thermal Therapy of Cancer: The Kinetics of Cell Death and Effect on Cell Cycle

Despite considerable advances in nano-photo-thermal therapy (NPTT), there have been a few studies reporting in-depth kinetics of cell death triggered by such a new modality of cancer treatment. In this study, we aimed to (1) investigate the cell death pathways regulating the apoptotic responses to NPTT; and (2) ascertain the effect of NPTT on cell cycle progression. Folate conjugated gold nanoparticle (F-AuNP) was firstly synthesized, characterized and then assessed to determine its potentials in targeted NPTT. The experiments were conducted on KB nasopharyngeal cancer cells overexpressing folate receptors (FRs), as the model, and L929 normal fibroblast cells with a low level of FRs, as the control. Cytotoxicity was evaluated by MTT assay and the cell death mode (i.e., necrosis or apoptosis) was determined through AnnexinV/FITC-propidium iodide staining. Next, the gene expression profiles of some key apoptotic factors involved in the mitochondrial signaling pathway were investigated using RT-qPCR. Finally, cell cycle phase distribution was investigated at different time points post NPTT using flow cytometric analysis. The obtained results showed that KB cell death following targeted NPTT was greater than that observed for L929 cells. The majority of KB cell death following NPTT was related to apoptosis. RT-qPCR analysis indicated that the elevated expression of Bax along with the depressed expression of Bcl-xL, Survivin and XIAP may involve in the regulation of apoptosis in response to NPTT. Flow cytometric analysis manifested that 16-24 hours after NPTT, the major proportion of KB cells was in the most radiosensitive phases of the cell cycle (G2/M). This study extended the understanding of the signaling pathway involved in the apoptotic response to NPTT. Moreover, the potential effect of NPTT on sensitizing cancer cells to subsequent radiation therapy was highlighted.

Clearable Black Phosphorus Nanoconjugate for Targeted Cancer Phototheranostics.

Therapeutic efficacy of synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) is limited by complex conjugation chemistry, absorption wavelength mismatch, and inadequate biodegradability of the PDT-PTT agents. Herein, we designed biocompatible copper sulfide nanodot anchored folic acid-modified black phosphorus nanosheets (BP-CuS-FA) to overcome these limitations, consequently enhancing the therapeutic efficiency of PDT-PTT. In vitro and in vivo assays reveal good biocompatibility and commendable tumor inhibition efficacy of the BP-CuS-FA nanoconjugate because of the synergistic PTT-PDT mediated by near-infrared laser irradiation. Importantly, folic acid unit could target folate receptor overexpressed cancer cells, leading to enhanced cellular uptake of BP-CuS-FA. BP-CuS-FA also exhibits significant contrast effect for photoacoustic imaging, permitting its in vivo tracking. The photodegradable character of BP-CuS-FA is associated with better renal clearance after the antitumor therapy in vivo. The present research may facilitate further development on straightforward approaches for targeted and imaging-guided synergistic PDT-PTT of cancer.

Folic acid-modified Laponite®-stabilized Fe3O4 nanoparticles for targeted T2-weighted MR imaging of tumor

In this study, a targeted T2-weighted MR imaging agent based on laponite (LAP) was constructed for cancer cells overexpressing folate receptors. Firstly, LAP stabilized Fe3O4 NPs are synthesized by a controlled co-precipitation route, and then amphiphilic copolymer poly(lactic acid)-poly(ethylene glycol) (PLA-PEG-COOH) is assembled on the surface of LAP/Fe3O4 NPs to provide additional stability, followed by the conjugate of folic acid modified generation 2 polyamidoamine dendrimer (G2-FA) via EDC coupling chemistry. The formed LAP/Fe3O4-PLA-PEG-G2-FA NPs can display good colloidal stability and an enhanced r2 relaxivity of 327.6 mM−1 s−1. In vitro experiments demonstrate that the hybrid nanoparticles are cytocompatible in the studied concentration range, and could specific target cancer cells with FA receptors overexpression. Finally, the xenografted tumor model experiment verifies that LAP/Fe3O4-PLA-PEG-G2-FA NPs can significantly reduce the MR signal of tumor site by specific accumulation, and be metabolized from the mice within 24 h. Therefore, LAP/Fe3O4-PLA-PEG-G2-FA NPs with good biocompatibility, a high r2 relaxivity, and FA targetability show a huge potential as a targeted T2-weighted MR imaging contrast for the early diagnosis of tumors overexpressing FA receptors.

In Situ Synthesis of Fluorescent Mesoporous Silica\u2013Carbon Dot Nanohybrids Featuring Folate Receptor-Overexpressing Cancer Cell Targeting and Drug Delivery

HighlightsA one-pot method was developed for the preparation of fluorescent mesoporous silica nanoparticles–carbon dots (MSNs–CDs) nanohybrid.The MSNs–CDs nanohybrid showed stable and bright yellow emission, excellent biocompatibility, and specific targeting capability toward folate receptor-overexpressing cancer cells and can be applied as fluorescence imaging-guided drug carriers for effectively delivering anticancer drugs to tumor sites.

Novel one pot synthesis and spectroscopic characterization of a folate-Mn3O4 nanohybrid for potential photodynamic therapeutic application.

Treatment of cancer using nanoparticles made of inorganic and metallic compounds has been increasingly used, owing to their novel intrinsic physical properties and their potential to interact with specific cellular sites, thereby significantly reducing severe secondary effects. In this study, we report a facile strategy for synthesis of folate capped Mn3O4 nanoparticles (FA-Mn3O4 NPs) with high colloidal stability in aqueous media using a hydrothermal method for potential application in photodynamic therapy (PDT) of cancer. The capping of FA to Mn3O4 NPs was confirmed using various spectroscopic techniques. In adenocarcinomic human alveolar basal epithelial cells (A549), the nanohybrid synthesised with a combination of FA and Mn3O4 shows remarkable PDT activity via intracellular ROS generation (singlet oxygen). As established by a DNA fragmentation assay and fluorescence studies, the nanohybrid can cause significant nuclear DNA damage by light induced enhanced ROS generation. In the assessment of Bax, Bcl2 provides strong evidence of apoptotic cellular death. Cumulatively, the outcomes of this study suggest that these newly synthesized FA-Mn3O4 NPs can specifically destroy cells with overexpressed folate receptors, thereby providing a solution in the journey of cancer eradication.

Folic Acid-Functionalized Gold Nanorods for Controlled Paclitaxel Delivery: In Vitro Evaluation and Cell Studies.

Short gold nanorods were synthesized (average length 28.08nm, average aspect ratio 3.54), which were functionalized with folic acid (FA) and 8-mercaptooctanoic acid (MOA) or 11-mercaptoundecanoic acid (MDA) and loaded with paclitaxel (PCT). FA was conjugated to the nanorods in order to render them targetable for cancer cells overexpressing folate receptors whereas MOA or MDA was attached on the nanorods in order to generate extra hydrophobic areas for entrapment of hydrophobic drugs such as PCT in the nanorods and in order to provide free carboxylic groups, which would allow for the conjugation of drug or other biofunctional molecules to the nanorods. The functionalized gold nanorods (GNRs-MOA-FA and GNRs-MDA-FA) did not exhibit any significant degree of aggregation in cell culture medium and blood plasma even after a prolonged incubation period of 7days, indicating the adequate colloidal stability of the nanorods in these media. The functionalized nanorods exhibited satisfactory entrapment efficiency (around 40%) for PCT and released less than 25% of their PCT content in phosphate buffer pH 7.4 in 48h. PCT entrapment efficiency was a little higher and PCT release rate a little lower in the GNRs-MOA-FA. Molecular analysis (qPCR) was used to find out that the MDA-MB-231 cancer cell line expresses the folate receptor (FL1R) whereas the MCF-7 cancer cell line does not. The PCT-loaded GNRs-MOA-FA were more cytotoxic than the PCT-loaded GNRs-MOA nanorods against the MDA-MB-231 cells, which probably relates to the higher uptake of the GNRs-MOA-FA nanorods by these cells. The opposite was true in the case of the MCF-7 cells.