Preparation, characterization, and in vitro targeted delivery of folate-decorated paclitaxel-loaded bovine serum albumin nanoparticles.
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ABSTRACT:
SUBMITTER: Zhao D
PROVIDER: S-EPMC2948946 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundTo prepare sorafenib-loaded folate-decorated bovine serum nanoparticles (FA-SRF-BSANPs) and investigate their effect on the tumor targeting.MethodsThe nanoparticles were characterized and evaluated by in vivo and in vitro experiments.ResultsSRF-loaded BSA nanoparticles (SRF-BSANPs) was first prepared and modified with folic acid by chemical coupling to obtain FA-SRF-BSANPs. The average particle size, zeta potential, entrapment efficiency, and drug loading of the optimized FA-SRF-BSANPs were 158.00 nm, -16.27 mV, 77.25%, and 7.73%, respectively. The stability test showed that FA-SRF-BSANPs remained stable for more than 1 month at room temperature. The TEM analysis showed that the surface of FA-SRF-BSANPs was nearly spherical. XRD analysis showed that the drug existed in. the nanoparticles in an amorphous state. FA-SRF-BSANPs can promote the intracellular uptake of hepatoma cells (SMMC-7721) with the strongest inhibitory effect compared with SRF-BSANPs and sorafenib solution. Furthermore, the tumor targeting of FA-SRF-BSANPs (Ctumor/Cblood, 0.666 ± 0.053) was significantly higher than those of SRF-BSANPs (Ctumor/Cblood, 0.560 ± 0.083) and sorafenib-solution (Ctumor/Cblood, 0.410 ± 0.038) in nude mice with liver cancer.ConclusionFA-modified albumin nanoparticles are good carriers for delivering SRF to the tumor tissue, which can improve the therapeutic effect and reduce the side effects of the drug.
| S-EPMC6374969 | biostudies-literature
Project description:Among the different ways to reduce the secondary effects of antineoplastic drugs in cancer treatment, the use of nanoparticles has demonstrated good results due to the protection of the drug and the possibility of releasing compounds to a specific therapeutic target. The α-isoform of the folate receptor (FR) is overexpressed on a significant number of human cancers; therefore, folate-targeted crosslinked nanoparticles based on BSA and alginate mixtures and loaded with paclitaxel (PTX) have been prepared to maximize the proven antineoplastic activity of the drug against solid tumors. Nanometric-range-sized particles (169 ± 28 nm-296 ± 57 nm), with negative Z-potential values (between -0.12 ± 0.04 and -94.1± 0.4), were synthesized, and the loaded PTX (2.63 ± 0.19-3.56 ±0.13 µg PTX/mg Np) was sustainably released for 23 and 27 h. Three cell lines (MCF-7, MDA-MB-231 and HeLa) were selected to test the efficacy of the folate-targeted PTX-loaded BSA/ALG nanocarriers. The presence of FR on the cell membrane led to a significantly larger uptake of BSA/ALG-Fol nanoparticles compared with the equivalent nanoparticles without folic acid on their surface. The cell viability results demonstrated a cytocompatibility of unloaded nanoparticle-Fol and a gradual decrease in cell viability after treatment with PTX-loaded nanoparticle-Fol due to the sustainable PTX release.
| S-EPMC8272094 | biostudies-literature
Project description:PurposeKRAS is the most frequently mutated gene in human cancers. Despite its direct involvement in malignancy and intensive effort, direct inhibition of KRAS via pharmacological inhibitors has been challenging. RNAi induced knockdown using siRNAs against mutant KRAS alleles offers a promising tool for selective therapeutic silencing in KRAS-mutant lung cancers. However, the major bottleneck for clinical translation is the lack of efficient biocompatible siRNA carrier systems.MethodsBovine serum albumin (BSA) nanoparticles were prepared by desolvation method to deliver siRNA targeting the KRAS G12S mutation. The BSA nanoparticles were characterized with respect to their size, zeta potential, encapsulation efficiency and nucleic acid release. Nanoparticle uptake, cellular distribution of nucleic acids, cytotoxicity and gene knock down to interfere with cancer hallmarks, uncontrolled proliferation and migration, were evaluated in KRAS G12S mutant A459 cells, a lung adenocarcinoma cell line.ResultsBSA nanoparticles loaded with siRNA resulted in nanoparticles smaller than 200 nm in diameter and negative zeta potentials, displaying optimal characteristics for in vivo application. Encapsulating and protecting the siRNA payload well, the nanoparticles enabled transport to A549 cells in vitro, could evade endosomal entrapment and mediated significant sequence-specific KRAS knockdown, resulting in reduced cell growth of siRNA transfected lung cancer cells.ConclusionsBSA nanoparticles loaded with mutant specific siRNA are a promising therapeutic approach for KRAS-mutant cancers.
| S-EPMC7611029 | biostudies-literature
Project description:The blood-brain barrier (BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme (GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel (PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles (NPs). Here we characterize PTX-loaded human serum albumin (HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P (SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content (7.89%) and entrapment efficiency (85.7%) with a spherical structure (about 150 nm) and zeta potential of -12.0 mV. The in vitro drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells (BCECs) and U87 cells was greatly improved. The low IC50, prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment.
| S-EPMC5985627 | biostudies-literature
Project description:Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a worse prognosis than other types. There are currently no specific approved treatments for TNBC. Albumin is a promising biomimetic material that may be fabricated into nanoparticles to possibly exert passive effects on targeted tumors. Irinotecan has been extensively used in clinical settings, although a high dosage is required due to its low efficiency of conversion into the active metabolite SN-38, also known as 7-ethyl-10-hydroxy-camptothecin. The aim of this work was to optimize SN-38-loaded bovine serum albumin nanoparticles (sBSANPs) and evaluate their potency against TNBC. The sBSANPs were characterized by a small size of about 134-264 nm, a negative charge of -37 to -40 mV, an entrapment efficiency of 59-71%, and a particle yield of 65-86%. The cytotoxicity assays using sBSANPs showed a higher potency specifically against both MDA-MB-468 and MDA-MB-231 cells (ER-, PR-, HER2-) compared to MCF-7 (ER+, PR+, HER2-), and exhibited an extremely low IC50 at the nanomolar levels (2.01-6.82 nM). The release profiles indicated that SN-38 presented an initial burst release within 12 h, and sBSANPs had a slow release pattern. Flow cytometry results showed that the fluorescence intensity of sBSANPs was significantly higher than that of the control group. The confocal images also confirmed that sBSANPs were taken up by MDA-MB-468 cells. Moreover, we found that a larger BSANP size resulted in an increased hemolytic effect. In vivo animal studies demonstrated that loading of SN-38 into bovine serum albumin nanoparticles could minimize the initial concentration without extending the elimination half-life, but significantly minimized the Cmax (p < 0.001) as compared with irinotecan treatment.
| S-EPMC6920977 | biostudies-literature
Project description:: Amphiphilic copolymers of stearic acid (SA)-modified Bletilla striata polysaccharides (BSPs-SA) with three different degrees of substitution (DSs) were synthesized. The effects of DS values on the properties of BSPs-SA nanoparticles were evaluated. Drug state, cytotoxicity, and histological studies were carried out. The affinity ability of bovine serum albumin (BSA) and the BSPs-SA nanoparticles was also characterized utilizing ultraviolet and fluorescence spectroscopy. Besides, the bioavailability and tissue distribution of docetaxel (DTX)-loaded BSPs-SA nanoparticles were also assessed. The results demonstrated that the DS increase of the hydrophobic stearic acid segment increased the negative charge, encapsulation efficiency, and drug-loading capacity while decreasing the critical aggregation concentration value as well as the release rate of docetaxel from the nanoparticles. Docetaxel was encapsulated in nanoparticles at the small molecules or had an amorphous status. The inhibitory capability of DTX-loaded BSPs-SA nanoparticles against 4T1 tumor cells was superior to that of Duopafei®. The ultraviolet and fluorescence results exhibited a strong binding affinity between BSPs-SA nanoparticles and bovine serum albumin, but the conformation of bovine serum albumin was not altered. Additionally, the area under the concentration⁻time curve (AUC₀⁻∞) of DTX-loaded BSPs-SA nanoparticles was about 1.42-fold higher compared with Duopafei® in tumor-bearing mice. Docetaxel levels of DTX-loaded BSPs-SA nanoparticles in some organs changed, and more docetaxel accumulated in the liver, spleen, and the tumor compared with Duopafei®. The experimental results provided a theoretical guidance for further applications of BSPs-SA conjugates as nanocarriers for delivering anticancer drugs.
| S-EPMC6358745 | biostudies-literature
Project description:Background:Melanoma is the most common symptom of aggressive skin cancer, and it has become a serious health concern worldwide in recent years. The metastasis rate of malignant melanoma remains high, and it is highly difficult to cure with the currently available treatment options. Effective yet safe therapeutic options are still lacking. Alternative treatment options are in great demand to improve the therapeutic outcome against advanced melanoma. This study aimed to develop albumin nanoparticles (ANPs) coated with macrophage plasma membranes (RANPs) loaded with paclitaxel (PTX) to achieve targeted therapy against malignant melanoma. Methods:Membrane derivations were achieved by using a combination of hypotonic lysis, mechanical membrane fragmentation, and differential centrifugation to empty the harvested cells of their intracellular contents. The collected membrane was then physically extruded through a 400 nm porous polycarbonate membrane to form macrophage cell membrane vesicles. Albumin nanoparticles were prepared through a well-studied nanoprecipitation process. At last, the two components were then coextruded through a 200 nm porous polycarbonate membrane. Results:Using paclitaxel as the model drug, PTX-loaded RANPs displayed significantly enhanced cytotoxicity and apoptosis rates compared to albumin nanoparticles without membrane coating in the murine melanoma cell line B16F10. RANPs also exhibited significantly higher internalization efficiency in B16F10 cells than albumin nanoparticles without a membrane coating. Next, a B16F10 tumor xenograft mouse model was established to explore the biodistribution profiles of RANPs, which showed prolonged blood circulation and selective accumulation at the tumor site. PTX-loaded RANPs also demonstrated greatly improved antitumor efficacy in B16F10 tumor-bearing mouse xenografts. Conclusion:Albumin-based nanoscale delivery systems coated with macrophage plasma membranes offer a highly promising approach to achieve tumor-targeted therapy following systemic administration.
| S-EPMC7090179 | biostudies-literature
Project description:BackgroundTrunk-boring pests (TBPs) are an important type of forest pest, TBPs not only feed on the branches and trunks of trees, but also spread quarantine diseases in forests. However, because the larvae of TBPs live inside the trunk and are well concealed, prevention and control are difficult. The lack of effective control methods leads to the death of many trees in forests. In this study, a novel nanopesticide featuring high bioactivity and slow-release properties was developed to control TBPs. Thiacloprid (THI), which is commonly used to control Coleoptera species, was used as a model pesticide.ResultsThe oleophobic properties of bovine serum albumin (BSA) were exploited to encapsulate the hydrophobic pesticide THI by self-assembly, and the size of the obtained nanoparticles, THI@BSA·NPs, was approximately 23 nm. The loading efficiency reached 70.4%, and THI@BSA·NPs could be released continuously for over 15 days, with the cumulative release reaching 93.5%. The fluorescein isothiocyanate (FITC)-labeled nanoparticles were evenly distributed in the digestive tract and body surface of a typical TBPs, M. alternatus, and the stomach and contact toxicities increased by 33.7% and 25.9%, respectively, compared with those of free THI. Furthermore, the results showed that the transport efficiency of THI@BSA·NPs was highest at a concentration of 50 ?g/mL, and the THI@BSA·NPs content in the trunk, from to lower to higher layers, was 8.8, 8.2, 7.6, and 5.8 ?g/g. At the same time, THI@BSA·NPs also exhibited high transport efficiency in dead trees.ConclusionThe transport efficiency and toxicity of the active ingredients are the key factors for the control of TBPs. This work provided idea for the application of biological delivery system encapsulated hydrophobic pesticides. The novel self-assembled THI@BSA·NPs have promising potential for sustainable control of TBPs.
| S-EPMC7653776 | biostudies-literature
Project description:In this work, we prepared a stimuli-responsive system for drug delivery and controlled release by engineering the bovine serum albumin (BSA). The doxorubicin (DOX)-loaded BSA nanoparticles (NPs) were conveniently prepared using desolvation method, followed by crosslinking through Schiff base bonds, leading to pH-sensitive DOX-loaded system (DOXs@BSA NPs). The resulted DOXs@BSA NPs showed high drug loading capacity (21.4%), and the particle size was about 130 nm with narrow polydispersity and high negative surface charge (-20.5 mV). The pH-sensitivity of DOXs@BSA NPs was evidenced by the size changes and charge reversal after incubation at different pH values. The DOXs@BSA NPs showed high serum stability which indicated the prolonged circulation time. The in vitro drug release experiment showed that the release of DOX was obviously accelerated by acidity because of disassembly of NPs induced by cleavage of Schiff base bonds. The drug release mechanism was thoroughly studied using a semi-empirical model, further confirming the pH played an important role in drug controlled release process. The results of cytotoxicity assay revealed that DOXs@BSA NPs exhibited much higher toxic effects for tumor cells in comparison to the free DOX control. Collectively, these results demonstrated that DOXs@BSA NPs might be potential application for drug delivery and controlled release in cancer chemotherapy. Moreover, this work also showed that preparation of stimuli-responsive drug delivery system by engineering the commercial biomaterials could be a promising method to develop multi-functional nanomedicine.
| S-EPMC7470134 | biostudies-literature
Project description:In this study, we investigated the active targeted delivery of a hydrophobic drug, paclitaxel (PTX), via receptor-mediated endocytosis by folate receptors expressed on cancer cells using a protein-based nanoparticle system. PTX was loaded on zein nanoparticles and conjugated with folate (PTX/Zein-FA) to estimate its chemotherapeutic efficacy in folate receptor-expressing KB cancer cells. PTX/Zein-FA nanoparticles were successfully developed, with a nanoparticle size of ~180 nm and narrow polydispersity index (~0.22). Accelerated release of PTX in an acidic environment was observed for PTX/Zein-FA. An in vitro cellular study of PTX/Zein-FAs in KB cells suggested that PTX/Zein-FA improved the cytotoxic activity of PTX on folate receptors overexpressed in cancer cells by inducing proapoptotic proteins and inhibiting anti-apoptotic proteins. In addition, PTX/Zein-FA exhibited anti-migratory properties and could alter the cell cycle profile of KB cells. A549 cells, which are folate receptor-negative cancer cells, showed no significant enhancement in the in vitro cellular activities of PTX/Zein-FA. We describe the antitumor efficacy of PTX/Zein-FA in KB tumor-bearing mice with minimum toxicity in healthy organs, and the results were confirmed in comparison with free drug and non-targeted nanoparticles.
| S-EPMC6920870 | biostudies-literature