Folate Nanoparticles Research Articles

CO-delivery of paclitaxel and indocyanine green with Koliphore-elp35/folic acid nanoparticles for NIR-triggered chemo/photodynamic therapy in MCF-7 and MCF-10 cells

Drug delivery with photodynamic therapy may improve breast cancer treatment. Drug delivery based polymeric nanoparticles, especially those made from natural polysaccharides, are promising cancer treatment carriers due to their biocompatibility and potential. This study involved the synthesis of Koliphore-elp35/Folic Acid-conjugated (KoliFA) nanoparticles for the concurrent delivery of paclitaxel and the photosensitizer indocyanine green (ICG) to breast cancer cells, aiming to improve the effectiveness of combined chemotherapy and PDT by using near-infrared (NIR) laser to activate the treatment. The cancer MCF-7 and normal MCF-10 breast cell lines were exposed to the nanoparticle formulation. The MTT assay evaluated the cytotoxic effects and established the IC50 values. The result showed that KoliFA is a near sphere-shaped particle with the average size of core KoliFA 390 nm and a layer of FA on the outer side of the nanoparticles its size increased to 1372 nm after loading PTX, and the zeta potential of KoliFA −12.5 mV decreased to −11mV after loading. The cytotoxicity of the KoliFA-PTX-ICG in MCF-7 cells increased, and reducing IC50 to 9.360 μg/ml compared to MCF-10 cells, this decrease suggests that PDT effect of ICG is a key factor in improving treatment efficacy by increasing ROS generation and increased sensitivity to treatment. Flow cytometry indicated increased apoptosis in MCF-7 cells after treatment with KoliFA-PTX-ICG + NIR laser. This study demonstrated that the KoliFA-PTX-ICG could be a promising platform for combination chemo-photodynamic therapy for breast cancer treatment.

Exploration of polydopamine capped bimetallic oxide (CuO-NiO) nanoparticles inspired by mussels for enhanced and targeted paclitaxel delivery for synergistic breast cancer therapy

Integration of antitumor drug and metallic nanoparticles in a polymeric nanosystem with effective properties is an emerging and promising tool to improve tumor treatment. Nevertheless, there is still a clinical need for multifunctional nanoparticles (NPs) to be developed for an “all-in-one” platform with specific targeting, less side effects and high therapeutic efficacy. In this research, pH-responsive bimetallic oxide-multifunctional NPs wrapped by polydopamine polymer for simultaneous cancer cell targeting and drug delivery were synthesized based on simple metal nanoparticle-ligand interactions. We explored a unique nanosystem of mussel inspired, polydopamine complexed with copper/nickel oxide NPs (CuO-NiO@PDA NPs). CuO-NiO@PDA NPs were then loaded with anticancer drug paclitaxel (PTX) via electrostatic or π-π stacking interaction and functionalized with folic acid (FA), a tumor-targeting ligand, to form CuO-NiO@PDA-PTX/FA NPs. Results highlight therapeutic potential of CuO-NiO@PDA/FA NPs as paclitaxel delivery nanocarrier in breast cancer therapy with sustained drug release pattern due to their increased stability, biocompatibility and antitumor efficacy. Cell viability was demonstrated in vitro using AO/EB dual staining, and its anticancer potential was confirmed by a reactive oxygen species (ROS) assay and mitochondrial membrane potential staining experiments. Consequently, our designed CuO-NiO@PDA-PTX/FA NPs appear to be promising multipurpose nanocarriers with therapeutic potential for MCF-7 tumor targeting and penetration.

Calcium Folate Nanoparticles as Dual‐Functional Neural Inducing Factors to Promote the Differentiation of Neural Stem Cells into Cholinergic Neurons

AbstractAlzheimer's disease (AD) features the loss of cholinergic neurons in the mesopontine area. There is no available approach to repair the damaged cholinergic neurons. Neural stem cell (NSC)‐based therapy is a promising strategy for the treatment of AD. However, it is a challenge to direct the NSCs to specifically differentiate into cholinergic neurons. Herein, calcium folate (CaFO) nanoparticles are synthesized through a facile nanoprecipitation approach for promoting the differentiation of NSCs into functional cholinergic neurons. After uptake by NSCs, the CaFO nanoparticles are distributed in the lysosomes (pH< 5.5) and can be decomposed into Ca2+ and folic acid in the acidic environment. The Ca2+ can accelerate the differentiation rate of NSCs while the folic acid can direct the NSCs to differentiate into cholinergic neurons. The in vitro experiments demonstrate that under the stimulation of CaFO nanoparticles, the NSCs differentiate into functional cholinergic neurons within 5 d. Animal experiments prove that the CaFO nanoparticles also promote the neuronal differentiation of NSCs in vivo, leading to the improvement in the cognitive memory ability of AD mice. This study provides a new strategy to induce the quick differentiation of NSCs into functional cholinergic neurons, which is promising for the treatment of AD.

Toxicity of Cisplatin and Herbal Medicine Complexed with Bovine Serum Albumin (BSA) and Folic Acid Nanoparticles as Anticancer Candidates

The prevalence of cancer in Indonesia has increased by 8.8 percent in the last two years (2018 and 2020) in terms of adding new cases and mortality. Because of therefor cancer treatment becomes important in reducing the high number of additional new cases and mortality due to cancer patients. Intensive cancer treatment is by surgery, chemotherapy, radiotherapy and immunotherapy. Chemotherapy drugs used for cancer treatment include herbal plant-based cancer drugs (Cancer Fit) and cisplatin its buy from online shop. This study aims to compare the toxicity of herbal drugs (Cancer fit) with cisplatin, a combination of BSA nanoparticles and folic acid as anticancer candidates. The research method is through the synthesis of nanoparticles with the desolvation method, then characterization is carried out using XRD and FT-IR tests. After that proceed to the toxicity test with the BSLT method. The results obtained from XRD analysis on BSA and folic acid nanoparticles from cisplatin (As-NP-BSA-CP) showed a peak of 34.45 while BSA and folic acid nanoparticles from herbal medicine (As-NP-BSA-Oh) obtained a peak of 22.77. The purpose of XRD analysis was to determine the crystalline characteristics of the synthesized nanoparticles and to analyze the crystalline index. FT-IR analysis on (As-NP-BSA-CP) showed that there are functional groups O-H alcohol, C-H, C-C, NO2 that play a role in the synthesis of nanoparticles. Meanwhile, (As-NP-BSA-Oh) showed that the functional groups were C-H alkene, C-O alcohol, and C-N amine/amide. The toxicity level of As-NP-BSA-CP LC50 is 69.14 ppm while the toxicity level of As-NP-BSA-Oh LC50 is 44.14 ppm. Nanoparticles consisting of a combination of bovine serum albumin (BSA), folic acid and cisplatin drugs or herbal drugs can be used as candidates for anticancer drugs.

Toxicity of Cisplatin and Herbal Medicine Complexed with Bovine Serum Albumin (BSA) and Folic Acid Nanoparticles as Anticancer Candidates

The prevalence of cancer in Indonesia has increased by 8.8 percent in the last two years (2018 and 2020) in terms of adding new cases and mortality. Because of therefor cancer treatment becomes important in reducing the high number of additional new cases and mortality due to cancer patients. Intensive cancer treatment is by surgery, chemotherapy, radiotherapy and immunotherapy. Chemotherapy drugs used for cancer treatment include herbal plant-based cancer drugs (Cancer Fit) and cisplatin its buy from online shop. This study aims to compare the toxicity of herbal drugs (Cancer fit) with cisplatin, a combination of BSA nanoparticles and folic acid as anticancer candidates. The research method is through the synthesis of nanoparticles with the desolvation method, then characterization is carried out using XRD and FT-IR tests. After that proceed to the toxicity test with the BSLT method. The results obtained from XRD analysis on BSA and folic acid nanoparticles from cisplatin (As-NP-BSA-CP) showed a peak of 34.45 while BSA and folic acid nanoparticles from herbal medicine (As-NP-BSA-Oh) obtained a peak of 22.77. The purpose of XRD analysis was to determine the crystalline characteristics of the synthesized nanoparticles and to analyze the crystalline index. FT-IR analysis on (As-NP-BSA-CP) showed that there are functional groups O-H alcohol, C-H, C-C, NO2 that play a role in the synthesis of nanoparticles. Meanwhile, (As-NP-BSA-Oh) showed that the functional groups were C-H alkene, C-O alcohol, and C-N amine/amide. The toxicity level of As-NP-BSA-CP LC50 is 69.14 ppm while the toxicity level of As-NP-BSA-Oh LC50 is 44.14 ppm. Nanoparticles consisting of a combination of bovine serum albumin (BSA), folic acid and cisplatin drugs or herbal drugs can be used as candidates for anticancer drugs.

Organometallic Folate Gold Nanoparticles Ameliorate Lipopolysaccharide-Induced Oxidative Damage and Inflammation in Zebrafish Brain.

Synthesized organometallic gold-based folate nanoparticles (FAuNPs) were characterized, and its defense against lipopolysaccharide (LPS)-induced brain inflammation in Zebra fish was proven. Vitamin entrapment efficiency of these particles was found to be nearly 70%. The in vitro pH-dependent drug release dialysis study of FAuNPs confirmed a slow, sustained, and gradual release of folate for a period of 24 h. Both AuNPs and FAuNPs did not cause any marked changes in food intake, body weight, color, behavioral pattern, blood parameters, and hepatotoxicity. Histology of liver showed no changes between treated and control groups of fishes. The ex vivo study showed significant uptake of FAuNPs to free folate in folate receptor negative Hek293 cells, confirming a strategy to overcome folate deficiency in the brain. Antioxidant status and activities of few crucial brain enzymes were also measured to assess the brain function and found to be returned to the basal level, following FAuNP treatment. The transcription factor NRF2-Keap 1 expression pattern was also noted, and a prominent modulation was observed in the LPS-treated and FAuNP-administered group. Decisive brain enzymes like AChE and Na+K+ATPase were decreased significantly after LPS treatment, which is restored with FAuNP treatment. Caspases increased sharply after LPS treatment and diminished following FAuNP treatment. We conclude that FAuNP due to its high physical stability and uptake could be utilized against severe brain inflammation, leading to brain injury and neurodegeneration.

Theranostic Effect of Folic Acid Functionalized MIL‐100(Fe) for Delivery of Prodigiosin and Simultaneous Tracking‐Combating Breast Cancer

The metal organic framework (MOF) member, MIL‐100(Fe), is considered as attractive drug nanocarrier that may be due to the great porosity, colloidal stability, and biocompatibility. In the present study, the new electrochemical synthesis procedure was presented for MIL‐100(Fe) building block, and secondly, folic acid (FA) was introduced to the structure for assessing its potential targeted ability to be entrapped by folic acid‐positive breast cancer cells, MCF‐7. Several techniques such as SEM, XRD, and FT‐IR were used to characterize synthesized nanostructures. Both MIL‐100(Fe) and MIL‐100(Fe)/FA nanoparticles were between 50 to 200 nm with a slightly positive net charge with an area of 1350 and 831.84 m2/g, respectively. The prodigiosin (PG) is selected as a model drug for MIL‐100(Fe) and MIL‐100(Fe)/FA‐targeted delivery owing to its natural fluorescence and cancer cell selectiveness. The loading capacity of both nanocarrier was around 40% with 93‐97% loading efficacy. Moreover, the pH‐sensitive prodigiosin release rate of MIL‐100(Fe)@PG and MIL‐100(Fe)/FA@PG showed that 69 to 73% of the drug was released after 24 hours in an acidic environment with around 20% unwanted leakage. The anticancer potential MIL‐100(Fe)/FA cells showed the improvement of selective index (SI) from 3.21 to 12.48 which means that folic acid acts as an effective ligand. The study of cells treated with fluorescence microscopy and flow cytometry analysis reveals the dependence of the receptor on the nanoparticle through endocytosis. Considering the effects of nanoparticles on healthy cells, MIL‐100(Fe) and MIL‐100(Fe)/FA nanoparticles can be introduced as targeted drug delivery systems for smart targeting breast cancer cells with minimal side effects.

Functionalized Folic Acid with Chitosan and PAMAM Dendrimers for Delivery of DNA and RNA

In this review, we explore the potential applications of functionalized folic acid-polymer nanoparticles in nucleic acids delivery. Folic acid-chitosan (carbohydrates) and folic acid-PAMAM (dendrimers) of different polymer sizes were used to conjugate with DNA and tRNA in vitro. Thermodynamic analysis showed that conjugation of DNA and tRNA to nanoparticles occurred via hydrophilic, hydrophobic, H-bonding and van der Waals contacts. Major alterations of DNA and RNA morphology occurred by nanocarrier interaction. These results indicate that functionalized folic acid-nanoparticles can deliver DNA and RNA to target sites.

Functionalization of Magnetic Nanoparticles by Folate as Potential MRI Contrast Agent for Breast Cancer Diagnostics.

In recent years, the intrinsic magnetic properties of magnetic nanoparticles (MNPs) have made them one of the most promising candidates for magnetic resonance imaging (MRI). This study aims to evaluate the effect of different coating agents (with and without targeting agents) on the magnetic property of MNPs. In detail, iron oxide nanoparticles (IONPs) were prepared by the polyol method. The nanoparticles were then divided into two groups, one of which was coated with silica (SiO2) and hyperbranched polyglycerol (HPG) (SPION@SiO2@HPG); the other was covered by HPG alone (SPION@HPG). In the following section, folic acid (FA), as a targeting agent, was attached on the surface of nanoparticles. Physicochemical properties of nanostructures were characterized using Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and a vibrating sample magnetometer (VSM). TEM results showed that SPION@HPG was monodispersed with the average size of about 20 nm, while SPION@SiO2@HPG had a size of about 25 nm. Moreover, HPG coated nanoparticles had much lower magnetic saturation than the silica coated ones. The MR signal intensity of the nanostructures showed a relation between increasing the nanoparticle concentrations inside the MCF-7 cells and decreasing the signal related to the T2 relaxation time. The comparison of coating showed that SPION@SiO2@HPG (with/without a targeting agent) had significantly higher r2 value in comparison to Fe3O4@HPG. Based on the results of this study, the Fe3O4@SiO2@HPG-FA nanoparticles have shown the best magnetic properties, and can be considered promising contrast agents for magnetic resonance imaging applications.

Preparation and characterization of lutein loaded folate conjugated polymeric nanoparticles

Aim To prepare and characterise lutein-loaded polylactide-co-glycolide–polyethylene glycol–folate (PLGA-PEG-FOLATE) nanoparticles and evaluate enhanced uptake in SK-N-BE(2) cells. Methods Nanoparticles were prepared using O/W emulsion solvent evaporation and characterised using DLS, SEM, DSC, FTIR and in-vitro release. Lutein-uptake in SK-N-BE(2) cells was determined using flow-cytometry, confocal-microscopy and HPLC. Control was lutein PLGA nanoparticles. Results The size of lutein-loaded PLGA and PLGA-PEG-FOLATE nanoparticles were 189.6 ± 18.79 nm and 188.0 ± 4.06 nm, respectively. Lutein entrapment was ∼61%(w/w) and ∼73%(w/w) for PLGA and PLGA-PEG-FOLATE nanoparticles, respectively. DSC and FTIR confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies showed ∼1.6 and ∼2-fold enhanced uptake of lutein from PLGA-PEG-FOLATE nanoparticles compared to PLGA nanoparticles and lutein, respectively. Cumulative release of lutein was higher in PLGA nanoparticles (100% (w/w) within 24 h) compared to PLGA-PEG-FOLATE nanoparticles (∼80% (w/w) in 48 h). Conclusion Lutein-loaded PLGA-PEG-FOLATE nanoparticles could be a potential treatment for hypoxic ischaemic encephalopathy.

PH-Sensitive Folic Acid Conjugated Alginate Nanoparticle for Induction of Cancer-Specific Fluorescence Imaging.

In cancer nanomedicine, numerous studies have been conducted on the surface modification and transport capacity of nanoparticles (NPs); however, biological barriers, such as enzymatic degradation or non-specific delivery during circulation, remain to be cleared. Herein, we developed pH-sensitive NPs that degrade in an acidic environment and release 5-aminolevulinic acid (5ALA) to the target site. NPs were prepared by conjugating alginate with folic acid, followed by encapsulation of 5ALA through a water-in-oil (W/O) emulsion method. The alginate-conjugated folic acid nanoparticles (AF NPs) were homogeneous in size, stable for a long time in aqueous suspension without aggregation, and non-toxic. AF NPs were small enough to efficiently infiltrate tumors (<50 nm) and were specifically internalized by cancer cells through receptor-mediated endocytosis. After the intracellular absorption of NPs, alginate was deprotonated in the lysosomes and released 5ALA, which was converted to protoporphyrin IX (PpIX) through mitochondrial heme synthesis. Our study outcomes demonstrated that AF NPs were not degraded by enzymes or other external factors before reaching cancer cells, and fluorescent precursors were specifically and accurately delivered to cancer cells to generate fluorescence.

Comparative study for optimization of folic acid nanoparticles

The present comparative study aims at studying the effect of several adjuvents on enhancing the stability and sustainability of FA NLCs which previously showed very promising results. The problem was encountered in the high drug release, high skin permeation, low deposition and low stability. In the present study, propylene glycol was added to all preparations as a stabilizer and coemulsifier. Plurol® stearique was utilized as solid lipid and stabilizer instead of apifil®. Soft paraffin was used as a softening additional lipid to Plurol® stearique to ensure the amorphous structure of NLCs. Liquid paraffin was used for its emollient effect instead of capryol ™ 90 with Apifil®. The in vitro drug release, ex vivo drug permeation and skin deposition were analyzed. Selection of the most optimum formulation is achieved to investigate its photostability, long term stability. Also, it was photographed under TEM. The selected formulation was stable after six hours of irradiation. The optimized selected formulation was successfully stable in refrigerator temperature throughout 9 months of the study. The TEM photograph reveals the formation of rounded nano vesicles. The present study was successful in development of more stable, more sustained means for topical delivery of FA for future cosmoceutical benefits.

Light-Addressable Nanoclusters of Ultrasmall Iron Oxide Nanoparticles for Enhanced and Dynamic Magnetic Resonance Imaging of Arthritis.

Design of novel nanoplatforms with single imaging elements for dynamic and enhanced T 1/T 2‐weighted magnetic resonance (MR) imaging of diseases still remains significantly challenging. Here, a facile strategy to synthesize light‐addressable ultrasmall Fe3O4 nanoparticles (NPs) that can form nanoclusters (NCs) under laser irradiation for enhanced and dynamic T 1/T 2‐weighted MR imaging of inflammatory arthritis is reported. Citric acid‐stabilized ultrasmall Fe3O4 NPs synthesized via a solvothermal approach are linked with both the arthritis targeting ligand folic acid (FA) and light‐addressable unit diazirine (DA) via polyethylene glycol (PEG) spacer. The formed ultrasmall Fe3O4‐PEG‐(DA)‐FA NPs are cytocompatible, display FA‐mediated targeting specificity to arthritis‐associated macrophage cells, and can form NCs upon laser irradiation to have tunable r 1 and r 2 relaxivities by varying the laser irradiation duration. With these properties owned, the designed Fe3O4‐PEG‐(DA)‐FA NPs can be used for T 1‐weighted MR imaging of arthritis without lasers and enhanced dual‐mode T 1/T 2‐weighted MR imaging of arthritis under laser irradiation due to the formation of NCs that have extended accumulation within the arthritis region and limited intravasation back to the blood circulation. The designed light‐addressable Fe3O4‐PEG‐(DA)‐FA NPs may be used as a promising platform for dynamic and precision T 1/T 2‐weighted MR imaging of other diseases.

Improved water dispersibility and photostability in folic acid nanoparticles with transglycosylated naringin using combined processes of wet-milling and freeze-drying.

We successfully prepared folic acid (FA) nanoparticles with excellent dispersibility and photostability using a combination of bead milling and freeze-drying with transglycosylated naringin (Naringin-G), a newly developed transglycosylated food additive. Poly-vinyl pyrrolidon (PVP) was used for comparison with Naringin-G. Water dispersibility and photostability of the freeze-dried formulations were assessed. The dispersibility and physicochemical properties of nanoparticle formulations were evaluated using dynamic light scattering, powder X-ray diffraction (PXRD), and small-angle X-ray scattering (SAXS). Results indicated that the median particle size of FA in the slurry bead milled with Naringin-G decreased notably with time and fell below 100 nm after milling for 300 min. Further, FA nanoparticles with Naringin-G were stable without aggregation following re-dispersion of freeze-dried FA formulations in water. Contrarily, the addition of PVP did not prevent the aggregation of FA nanoparticles following re-dispersion of freeze-dried FA formulations. Solid structures of freeze-dried FA formulations with Naringin-G or PVP were assessed using PXRD and SAXS. PXRD patterns of all freeze-dried formulations highlighted broadening and weakening of peaks, indicating a decrease in FA crystallinity following bead milling, regardless of the additive concentration of Naringin-G and PVP. The scattering intensity profiles of FA formulations with PVP dramatically decreased after milling, whereas FA formulations with Naringin-G did not exhibit changes in SAXS patterns. FA formulations with Naringin-G registered faster enhancement in release rate than PVP in pH 1.2 buffer solutions. The release rate of freeze-dried FA formulation with Naringin-G exhibited at least five-fold enhancement when compared to untreated FA. FA formulation with Naringin-G was stable to photodegradation under fluorescent light. Naringin-G prevented photodegradation of FA due to its antioxidant effect and scavenged radicals. These findings indicated that freeze-dried FA formulation with Naringin-G can improve its water-dispersibility and photodegradation due to the effectiveness of Naringin-G as a dispersant and cryoprotectant.

Multifunctional Dendrimer-Entrapped Gold Nanoparticles Conjugated with Doxorubicin for pH-Responsive Drug Delivery and Targeted Computed Tomography Imaging.

Novel theranostic nanocarriers exhibit a desirable potential to treat diseases based on their ability to achieve targeted therapy while allowing for real-time imaging of the disease site. Development of such theranostic platforms is still quite challenging. Herein, we present the construction of multifunctional dendrimer-based theranostic nanosystem to achieve cancer cell chemotherapy and computed tomography (CT) imaging with targeting specificity. Doxorubicin (DOX), a model anticancer drug, was first covalently linked onto the partially acetylated poly(amidoamine) dendrimers of generation 5 (G5) prefunctionalized with folic acid (FA) through acid-sensitive cis-aconityl linkage to form G5·NHAc-FA-DOX conjugates, which were then entrapped with gold (Au) nanoparticles (NPs) to create dendrimer-entrapped Au NPs (Au DENPs). We demonstrate that the prepared DOX-Au DENPs possess an Au core size of 2.8 nm, have 9.0 DOX moieties conjugated onto each dendrimer, and are colloid stable under different conditions. The formed DOX-Au DENPs exhibit a pH-responsive release profile of DOX because of the cis-aconityl linkage, having a faster DOX release rate under a slightly acidic pH condition than under a physiological pH. Importantly, because of the coexistence of targeting ligand FA and Au core NPs as a CT imaging agent, the multifunctional DOX-loaded Au DENPs afford specific chemotherapy and CT imaging of FA receptor-overexpressing cancer cells. The constructed DOX-conjugated Au DENPs hold a promising potential to be utilized for simultaneous chemotherapy and CT imaging of various types of cancer cells.

Optimizing the preparation and stability of decorated antiretroviral drug nanocrystals.

Aim:While the therapeutic potential for current long-acting (LA) antiretroviral therapy (ART) is undeniable, ligand-decorated nanoformulated LA-ART could optimize drug delivery to viral reservoirs. The development of decorated ART hinges, however, on formulation processes and manufacture efficiencies. To this end, we compared manufacture and purification techniques for ligand-decorated antiretroviral drug nanocrystals.Materials & methods:Ligand-decorated nanoparticle manufacturing was tested using folic acid (FA) nanoformulated cabotegravir.Results:Direct manufacturing of FA-cabotegravir resulted in stable particles with high drug loading and monocyte–macrophage targeting. A one step ‘direct’ scheme proved superior over differential centrifugation or tangential flow filtration facilitating particle stability and preparation simplicity and efficiency.Conclusion:Direct manufacturing of FA nanoparticles provides a path toward large-scale clinical grade manufacturing of cell-targeted LA-ART.

Folate receptor-targeted lipid-albumin nanoparticles (F-LAN) for therapeutic delivery of an Akt1 antisense oligonucleotide

Background: RX-0201 is an antisense oligonucleotide (ASO) against Akt1 currently in clinical trial for metastatic renal cancer.Purpose: To improve the delivery of RX-0201 using folate receptor-targeted lipid-albumin nanoparticles (F-LAN).Methods: F-LAN were synthesized with the composition of DOTAP/soyPC/TPGS/folate-PEG-DSPE (25:70:4:1 m/m), a cationic human serum albumin-pentaethylenehexamine (HSA-PEHA) conjugate and RX-0201. The nanoparticles were evaluated in KB human carcinoma cells in vitro and in a KB murine xenograft tumour model in vivo for pharmacokinetics and antitumor activities.Results: The F-LAN-RX-0201 had a mean particle size of 108.6 ± 5.8 nm, zeta potential of 10.5 ± 3.2 mV and ASO loading efficiency of 71.5 ± 4.5%. In KB cells, uptake and Akt1 inhibition by F-LAN-RX-0201 were greater than those of non-targeted LAN-RX-0201 and could be partially blocked by excess free folate. F-LAN-RX-0201 inhibited cell growth with an IC50 of 11.9 μM. In contrast, LAN-RX-0201 showed lower cytotoxicity with an IC50 of 32.0 μM. No significant cytotoxicity was observed with up to 250 µM of free RX-0201. Pharmacokinetic studies showed that F-LAN-RX-0201 had a longer terminal half-life than free RX-0201 (442 vs. 219 min). In a KB xenograft tumour model, F-LAN-RX-0201 exhibited greater tumour inhibition than LAN-RX-0201 at 16 mg/kg. Moreover, F-LAN-RX-0201 at 16 mg/kg showed comparable tumour inhibition compared to free RX-0201 at a much higher dose of 90 mg/kg.Conclusions: F-LAN-RX-0201 showed promise as a therapeutic agent for tumours with elevated folate-receptor expression.

Developing single-entity Theranostic: drug-based Fluorescent Nanoclusters With Augmented Cytotoxicity

To develop methotrexate (MTX) templated luminescent gold nanoclusters (NCs) as a single unit nanotheranostic for cancer therapy and to assess its potential as an alternative to the parent drug, for drug delivery vehicles (DDVs). Theranostics were synthesized and extensively characterized. The stability of the theranostic and its bioimaging aptitude were evaluated. The antiproliferative propensity of the theranostic was gauged with cell viability assays and was supplemented with cytometry-based assays. Feasibility of delivering the MTX NCs instead of parent drug on a DDV was also checked. MTX NCs displayed remarkable physical characteristics and augmented cytotoxicity with a robust stability in phosphate-buffered saline and serum. MTX NCs also demonstrated their amenability to being loaded on a DDV (chitosan folic acid nanoparticles) while retaining their physical and cytotoxic profile. Generation of next level drug-based theranostics with the potential of replacing the free drug in drug delivery platforms.

Functionalized Cu3BiS3 nanoparticles for dual-modal imaging and targeted photothermal/photodynamic therapy.

Multifunctional nano-biomaterials with the integration of diagnostic and therapeutic functions have shown great promise in improving the efficacy of cancer therapy. Herein, a new nanoplatform based on functionalized Cu3BiS3 nanoparticles (NPs) is fabricated for tumour-targeted combination phototherapy. The as-synthesized hydrophobic Cu3BiS3 NPs are modified with DSPE-PEG/DSPE-PEG-NH2, followed by the conjugation of the photosensitizer chlorin e6 (Ce6) and the target ligand folic acid (FA). The introduced Ce6 can further form a chelate complex with Gd3+. The rationally designed Cu3BiS3-PEG-(Ce6-Gd3+)-FA NPs, which have high physiological stability and good biocompatibility, can specifically target FA-receptor over-expressed tumour cells. The Cu3BiS3-PEG-(Ce6-Gd3+)-FA NPs exhibit effective dual-modal CT and MR imaging in the xenografted HeLa tumours. Importantly, excellent in vivo anti-tumour effects have been achieved by synergistic photothermal/photodynamic therapy using the multifunctional NPs. We expect that this versatile nanoplatform will play a role in exploring precise cancer diagnosis and therapy.

Fabrication of folic acid magnetic nanotheranostics: An insight on the formation mechanism, physicochemical properties and stability in simulated physiological media

Nanodevices based on magnetite functionalized with folic acid (FA) with improved properties to be employed as theranostics in various types of cancer are here proposed. Two methodologies for FA incorporation were explored aiming to reach suitable loading efficiency as well as adequate stability of nanosystems in physiological media. To this end, simple adsorption and covalent binding of FA and some experimental conditions derived from both procedures were studied. A thorough physicochemical characterization was performed using all the formulations. The mechanism of the interaction between FA and magnetite nanoparticles (MNPs) was elucidated from characterization results supported by theoretical studies using spin-polarized density functional theory (DFT). Both data coincide in that the selective functional group of FA (pteridine group) remained available after FA binding MNPs. Such studies also demonstrated that any of FA carboxylate groups could be available to potentially link other molecule (i.e therapeutic agents). Besides, other issues that are not normally accomplished in reported articles were included; i.e the stability according to two different criteria: size evolution (expressed as hydrodynamic diameter) as a function of time in aqueous media; and the capacity FA retention in PBS, pH=7.4. Recovered data indicated that the samples are stable at least 15days in water and 4h in buffer without significant modifications of their properties. The feasibility of these formulations to interact with simulated physiological fluid was also assayed. The results revealed that protein corona was formed around all the tested formulations leading to more stable nanodevices in terms of their hydrodynamic sizes and size evolution along the time. To complete the theranostic characteristic, Doxorubicin was added to the MNPs@FA by physical adsorption, to provide the therapeutic function. The satisfactory incorporation was verified by FTIR spectroscopy.