Search Results (156)

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

Background/Objectives: Magnetic iron oxide nanoparticles (IONPs), human serum albumin (HSA) and folic acid (FA) are prospective components for hybrid nanosystems for various biomedical applications. The magnetic nanosystems FA-HSA@IONPs (FAMs) containing IONPs, HSA, and FA residue are engineered in the study. Methods: Composition, stability and integrity of the coating, and peroxidase-like activity of FAMs are characterized using UV/Vis spectrophotometry (colorimetric test using o-phenylenediamine (OPD), Bradford protein assay, etc.), spectrofluorimetry, dynamic light scattering (DLS) and electron magnetic resonance (EMR). The selectivity of the FAMs accumulation in cancer cells is analyzed using flow cytometry and confocal laser scanning microscopy. Results: FAMs (d_N~55 nm by DLS) as a drug delivery platform have been administered to cancer cells (human breast adenocarcinoma MCF-7 and MDA-MB-231 cell lines) in vitro. Methylene blue, as a model photosensitizer, has been non-covalently bound to FAMs. An increase in photoinduced cytotoxicity has been found upon excitation of the photosensitizer bound to the coating of FAMs compared to the single photosensitizer at equivalent concentrations. The suitability of the nanosystems for photodynamic therapy has been confirmed. Conclusions: FAMs are able to effectively enter cells with increased folate receptor expression and thus allow antitumor photosensitizers to be delivered to cells without any loss of their in vitro photodynamic efficiency. Therapeutic and diagnostic applications of FAMs in oncology are discussed. Full article

Folic acid (FA) is used as a targeting ligand for targeted drug delivery to tumor cells, some types of which overexpress folate receptors on their surface. However, while the preparation of conjugates containing FA may comprise a multi-step process, FA presents low photostability under UV irradiation. In addition, FA undergoes radiolysis under the action of ionizing radiation, which is utilized for drug sterilization. In this study, we investigate the stability of FA in a conjugate (FA-PVP-C₆₀) with fullerene C₆₀ and polyvinylpyrrolidone under the action of UV (205–400 nm) and electron irradiation (doses from 2 to 8 kGy) at different pH (4.5, 7.2, 10.7). The degradation of FA is studied using fluorescence and UV–Vis spectroscopy. It is found that the fullerene C₆₀ in the FA-PVP-C₆₀ conjugate suppresses the degradation of FA during both photolysis and radiolysis, which is confirmed by the decrease in the quantum yield of fluorescence and the radiation chemical yield of FA destruction accompanied by increasing fullerene content in the conjugate (from 2.8 to 10 wt.%). Full article

In this study, we developed a multifunctional graphene oxide (GO)-based nanoprobe co-loaded with antisense peptide nucleic acid (PNA) and the chemotherapeutic agent doxorubicin (DOX). The nanoplatform was strategically functionalized with folic acid ligands to enable folate receptor-mediated tumor targeting. Upon cellular internalization, the antisense PNA component selectively hybridized with human telomerase reverse transcriptase (hTERT) mRNA through sequence-specific recognition, inducing structural detachment from the GO surface. This displacement restored the fluorescence signal of previously quenched fluorophores conjugated to the PNA strand, thereby enabling the real-time in situ detection and quantitative fluorescence imaging of intracellular hTERT mRNA dynamics. The antisense PNA component effectively reduced the hTERT mRNA level and downregulated telomerase activity via an antisense gene regulation pathway, while the pH-responsive release of DOX induced potent cancer cell apoptosis through chemotherapeutic action. This combinatorial therapeutic strategy demonstrated enhanced anticancer efficacy compared to single-modality treatments, achieving a 60% apoptosis induction in HeLa cells through coordinated gene silencing and chemotherapy. This study establishes GO as a promising dual-drug nanocarrier platform for developing next-generation theranostic systems that integrate molecular diagnostics with multimodal cancer therapy. Full article

To develop an efficient drug delivery system, we co-entrapped superparamagnetic Fe₃O₄ and the chemotherapeutic drug doxorubicin (DOX) in oleoyl-chitosan (OC) to prepare DOX-entrapped magnetic OC (DOX-MOC) nanoparticles (NPs) through ionic gelation of OC with sodium tripolyphosphate (TPP). The NPs provide magnetically targeted delivery of DOX in cancer therapy. Using folic acid (FA)-grafted OC, FA-conjugated DOX-entrapped magnetic OC (FA-DOX-MOC) NPs were prepared similarly for FA-mediated active targeting of cancer cells with overexpressed folate receptors. Considering DOX loading and release, the best conditions for preparing DOX-MOC NPs were an OC:TPP mass ratio = 1:4 and OC concentration = 0.2%. These spherical NPs had a particle size of ~250 nm, 87.9% Fe₃O₄ content, 53.1 emu/g saturation magnetization, 83.1% drug encapsulation efficacy, and 2.81% drug loading efficiency. FA did not significantly change the physico-chemical characteristics of FA-DOX-MOC compared to DOX-MOC, and both NPs showed pH-dependent drug release behaviors, with much faster release of DOX at acidic pH values found in endosomes. However, FA could enhance the intracellular uptake of the NPs and DOX accumulation in the nucleus. This active targeting effect led to significantly higher cytotoxicity towards U87 cancer cells. These results suggest that FA-DOX-MOC NPs can efficiently deliver DOX for controlled drug release in cancer therapy. Full article

Transition-metal ion copper(II) (Cu(II)) has drawn increasing attention as a small-molecular cancer theranostic agent. However, delivering a sufficient dosage of Cu(II) to the tumor site and integrating multiple imaging modalities to achieve precise and effective cancer theranostics remains a critical challenge. Herein, an emerging Cu(II)-based nanocomposite has been synthesized for targeted tumor computed tomography (CT)/magnetic resonance (MR) dual-mode imaging and chemodynamic therapy (CDT). Briefly, 2-picolinic acid (PA-COOH), polyethylene glycol (PEG)-linked folic acid (FA), and fluorescein isothiocyanate (FI) were sequentially conjugated with polyethylenimine (PEI.NH₂) and then in situ fabrication of gold nanoparticles (Au NPs) occurred within the PEI.NH₂ internal cavity. After acetylation of PEI.NH₂ terminal amines and Cu(II) complexation, the Cu(II)-based nanocomposites FA-Au/Cu(II) PENPs with a mean diameter of 2.87 nm were generated. The synthesized FA-Au/Cu(II) PENPs showed favorable stability of colloidal dispersion, sustainable Cu(II) release properties in a pH-dependent manner, and Fenton-like catalytic activity specifically. With the FA-mediated targeting pathway, FA-Au/Cu(II) PENPs can specifically accumulate in cancer cells with high expression of FA receptors. Meanwhile, the complementary CT/MR dual-mode imaging in vitro and in vivo can be afforded by FA-Au/Cu(II) PENPs based on the excellent X-ray attenuation properties of Au NPs and the applicable r₁ relaxivity (0.7378 mM⁻¹s⁻¹) of Cu(II). Notably, the Cu(II)-mediated CDT mechanism enables FA-Au/Cu(II) PENPs to elicit the generation of toxic hydroxyl radicals (·OH), depletion of glutathione (GSH), promotion of lipid peroxidation (LPO), and induction of cancer cell apoptosis in vitro, and further demonstrates remarkable anti-tumor efficacy in a xenograft tumor model. With the illustrated targeted theranostic capacity of FA-Au/Cu(II) PENPs towards tumors, this Cu(II)-based nanocomposite paradigm inspires the construction of advanced theranostic nanoplatforms incorporating alternative transition metal ions. Full article

Kidney fibrosis is the common pathological pathway in progressive chronic kidney disease (CKD), and current treatments are largely ineffective. The C-X-C chemokine receptor 4 (CXCR4) is crucial to fibrosis development. By using neural cell adhesion molecules as scaffolds with binding loops that mimic the shape of shark antibodies, fully humanized single-domain i-bodies have been developed. The first-generation i-body, AD-114, demonstrated antifibrotic effects in a mouse model of folic acid (FA)-induced renal fibrosis. The second-generation i-body, AD-214, is an Fc-fusion protein with an extended half-life, enhanced activity, and a mutated Fc domain to prevent immune activation. To investigate the renoprotective mechanisms of AD-214, RPTEC/TERT1 cells (a human proximal tubular cell line) were incubated with TGF-b1 with/without AD-214 and the supernatant was collected to measure collagen levels by Western blot. Mice with unilateral ureteral obstruction (UUO) received AD-214 intraperitoneally (i.p.) every two days for 14 days. Kidney fibrosis markers and kidney function were then analyzed. AD-214 suppressed TGF-b1-induced collagen overexpression in RPTEC/TERT1 cells. In UUO mice, AD-214 reduced extracellular matrix (ECM) deposition, restored kidney function, and limited leukocyte infiltration. In a scratch assay, AD-214 also inhibited macrophage migration. To conclude, i-body AD-214 attenuates UUO-induced kidney fibrosis by inhibiting leukocyte infiltration and macrophage migration. Full article

The most important issues in acute myeloid leukemia are preventing relapse and treating relapse. Although the remission rate has improved to approximately 80%, the 5-year survival rate is only around 30%. The main reasons for this are the high relapse rate and the limited treatment options. In chronic myeloid leukemia patients, when a deep molecular response is achieved for a certain period of time through tyrosine kinase inhibitor treatment, about half of them will reach treatment-free remission, but relapse is still a problem. Therefore, potential therapeutic targets for myeloid leukemias are eagerly awaited. Autophagy suppresses the development of cancer by maintaining cellular homeostasis; however, it also promotes cancer progression by helping cancer cells survive under various metabolic stresses. In addition, autophagy is promoted or suppressed in cancer cells by various genetic mutations. Therefore, the development of therapies that target autophagy is also being actively researched in the field of leukemia. In this review, studies of the role of autophagy in hematopoiesis, leukemogenesis, and myeloid leukemias are presented, and the impact of autophagy regulation on leukemia treatment and the clinical trials of autophagy-related drugs to date is discussed. Full article

Folate receptor alpha (FRα) is a glycosylphosphatidylinositol (GPI) membrane-anchored protein containing three N-glycosylated residues at the N47, N139, and N179 termini. These glycosylation sites have been reported to be crucial for the receptor’s structural integrity and its ability to bind and internalize FA. Here, we investigated the role of FRα glycosylation in the binding and internalization efficacy of FA–DABA–SMA in pancreatic PANC-1 cancer cells. There is a strong association of the FA copolymer with FRα with a Pearson coefficient R-value of 0.7179. PANC-1 cancer cells were pretreated with maackia amurensis lectin II (MAL-2), sambucus Nigra lectin (SNA-1), peanut agglutinin (PNA), and wheat germ agglutinin lectin (WGA) at different doses followed by 20 kDa and 350 kDa FA–DABA–SMA loaded with coumarin 153 (C153). Increasing the dosage of MAL2, SNA-1, PNA, and WGA concomitantly and significantly increased the internalization of C153-loaded FA–DABA–SMA in the cells. The half maximal effective lectin concentrations (EC50) to induce cellular internalization into the cytoplasm of the lectins for MAL-2 were 35.88 µg/mL, 3.051 µg/mL for SNA-1, 7.883 µg/mL for PNA, and 0.898 µg/mL for WGA. Live cell imaging of the internalization of 20 kDa and 350 kDa FA copolymers indicated an aggregation of 350 kDa copolymer with FRα in the cytoplasm. In contrast, the 20 kDa FA copolymer remained in the membrane. The data indicate for the first time that the mobile positions of the glycosyl radical groups and the receptor tilt in generating steric hindrance impacted the individual FRα receptors in the binding and internalization of 350 kDa FA–DABA–SMA in cancer cells. Full article

Background: Preeclampsia is a leading cause of pregnancy-related maternal and fetal morbidity and mortality. Although its precise cause and prevention remain unclear, risk factors such as overweight and inadequate nutrient intake (e.g., calcium, folic acid, and vitamin D) are known to increase its incidence. Recent research has focused on the genetic predisposition to preeclampsia, identifying polymorphisms that may affect enzyme or receptor function. This study aims to review existing literature examining the relationship between genetic polymorphisms, BMI (body mass index), and nutrient levels in preeclampsia to develop more actionable therapeutic strategies. Methods: A systematic review was conducted to analyze studies on the nutrigenetic relationship between BMI, micronutrients, and preeclampsia. Results: A total of 17 studies investigating 12 genes related to BMI and 10 studies exploring 3 genes in relation to micronutrient levels were included in the analysis. Several polymorphisms associated with preeclampsia were found to be influenced by maternal BMI or serum vitamin levels. The interactions between certain gene variants and these factors suggest that both BMI and micronutrient status may modify the risk of developing preeclampsia in genetically predisposed individuals. Conclusions: Our findings emphasize the potential for reanalyzing existing data by categorizing based on genotype and nutrient levels. This approach could yield more personalized dietary and therapeutic recommendations for managing preeclampsia. In the future, genetic information may support the development of tailored nutritional counseling during pregnancy to mitigate preeclampsia risk. Full article

Folic acid (FA) and its structural analog, anticancer medicine methotrexate (MTX), are known to form host/guest complexes with native cyclodextrins, of which the most stable are formed with the medium-sized β-cyclodextrin. Based on our research, proving that simple sugars (D-glucose, D-galactose, and D-mannose) can form adducts with folic acid, we envisioned that combining these two types of molecular receptors (cyclodextrin and simple carbohydrates) into one may be beneficial for the complexation of FA and MTX. We designed and obtained host/guest inclusion complexes of FA and MTX with two monoderivatives of β-cyclodextrin—substituted at position 6 with monosaccharide (glucose, G-β-CD) and disaccharide (maltose, Ma-β-CD). The complexation was proved by experimental (NMR, UV-vis, IR, TG, DSC) and theoretical methods. We proved that derivatization of β-cyclodextrin with glucose and maltose has a significant impact on the complexation with FA and MTX, as the addition of one glucose subunit to the structure of the receptor significantly increases the value of association constant for both FA/G-β-CD and MTX/G-β-CD, while further extending a pendant chain (incorporation of maltose subunit) results in no additional changes. Full article

Cellular metabolism is crucial for various physiological processes, with folate-dependent one-carbon (1C) metabolism playing a pivotal role. Folate, a B vitamin, is a key cofactor in this pathway, supporting DNA synthesis, methylation processes, and antioxidant defenses. In dividing cells, folate facilitates nucleotide biosynthesis, ensuring genomic stability and preventing carcinogenesis. Additionally, in neurodevelopment, folate is essential for neural tube closure and central nervous system formation. Thus, dysregulation of folate metabolism can contribute to pathologies such as cancer, severe birth defects, and neurodegenerative diseases. Epidemiological evidence highlights folate’s impact on disease risk and its potential as a therapeutic target. In cancer, antifolate drugs that inhibit key enzymes of folate-dependent 1C metabolism and strategies targeting folate receptors are current therapeutic options. However, folate’s impact on cancer risk is complex, varying among cancer types and dietary contexts. In neurodegenerative conditions, including Alzheimer’s and Parkinson’s diseases, folate deficiency exacerbates cognitive decline through elevated homocysteine levels, contributing to neuronal damage. Clinical trials of folic acid supplementation show mixed outcomes, underscoring the complexities of its neuroprotective effects. This review integrates current knowledge on folate metabolism in cancer and neurodegeneration, exploring molecular mechanisms, clinical implications, and therapeutic strategies, which can provide crucial information for advancing treatments. Full article

The advent of pH-sensitive liposomes (pHLips) has opened new opportunities for the improved and targeted delivery of antitumor drugs as well as gene therapeutics. Comprising fusogenic dioleylphosphatidylethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS), these nanosystems harness the acidification in the tumor microenvironment and endosomes to deliver drugs effectively. pH-responsive liposomes that are internalized through endocytosis encounter mildly acidic pH in the endosomes and thereafter fuse or destabilize the endosomal membrane, leading to subsequent cargo release into the cytoplasm. The extracellular tumor matrix also presents a slightly acidic environment that can lead to the enhanced drug release and improved targeting capabilities of the nano-delivery system. Recent studies have shown that folic acid (FA) and iRGD-coated nanocarriers, including pH-sensitive liposomes, can preferentially accumulate and deliver drugs to breast tumors that overexpress folate receptors and αvβ3 and αvβ5 integrins. This study focuses on the development and characterization of 5-Fluorouracil (5-FU)-loaded FA and iRGD surface-modified pHLips (FA-iRGD-5-FU-pHLips). The novelty of this research lies in the dual targeting mechanism utilizing FA and iRGD peptides, combined with the pH-sensitive properties of the liposomes, to enhance selective targeting and uptake by cancer cells and effective drug release in the acidic tumor environment. The prepared liposomes were small, with an average diameter of 152 ± 3.27 nm, uniform, and unilamellar, demonstrating efficient 5-FU encapsulation (93.1 ± 2.58%). Despite surface functionalization, the liposomes maintained their pH sensitivity and a neutral zeta potential, which also conferred stability and reduced aggregation. Effective pH responsiveness was demonstrated by the observation of enhanced drug release at pH 5.5 compared to physiological pH 7.4. (84.47% versus 46.41% release at pH 5.5 versus pH 7.4, respectively, in 72 h). The formulations exhibited stability for six months and were stable when subjected to simulated biological settings. Blood compatibility and cytotoxicity studies on MDA-MB-231 and SK-BR3 breast cancer cell lines revealed an enhanced cytotoxicity of the liposomal formulation that was modified with FA and iRGD compared to free 5-FU and minimal hemolysis. Collectively, these findings support the potential of FA and iRGD surface-camouflaged, pH-sensitive liposomes as a promising drug delivery strategy for breast cancer treatment. Full article

Mesoporous silica nanoparticles (MSNs) are promising drug carriers for cancer therapy. Their functionalization with ligands for specific tissue/cell targeting and stimuli-responsive cap materials for sealing drugs within the pores of MSNs is extensively studied for biomedical and pharmaceutical applications. The objective of the present work was to establish MSNs as ideal nanocarriers of anticancer drugs such as 5-FU and silymarin by exploiting characteristics such as their large surface area, pore size, and biocompatibility. Furthermore, coating with various biopolymeric materials such as carboxymethyl chitosan–dopamine and hyaluronic acid–folic acid on their surface would allow them to play the role of ligands in the process of active targeting to tumor cells in which there is an overexpression of specific receptors for them. From the results obtained, it emerged, in fact, that these hybrid nanoparticles not only inhibit the growth of glioblastoma and breast cancer cells, but also act as pH-responsive release systems potentially useful as release vectors in tumor environments. Full article

Glioblastoma (GBM) conventional treatment is not curative, and it is associated with severe toxicity. Thus, natural compounds with anti-cancer properties and lower systemic toxicity, such as gallic acid (GA), have been explored as alternatives. However, GA’s therapeutic effects are limited due to its rapid metabolism, low bioavailability, and low permeability across the blood–brain barrier (BBB). This work aimed to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with folic acid (FA), as its receptor is overexpressed in BBB and GBM cells, for GA delivery to enhance its therapeutic efficacy. The preparation of NPs was optimized by a central composite design (CCD). The obtained NPs showed physicochemical features suitable for drug internalization in BBB and tumor cells (sizes below 200 nm, monodispersity, and negative surface charge) and the ability to maintain a slow and sustained release for 40 days. In vitro studies using a human GBM cell line (U215) revealed the NPs’ ability to accumulate in the target cells, further promoting GA antiproliferative activity by inducing the production of intracellular reactive oxygen species (ROS). Furthermore, GA encapsulation in the developed nanosystems conferred higher protection to healthy cells. Full article