BSA-Encapsulated Morin Hydrate Nanoparticles Show Enhanced Anticancer Activity Against Colorectal Cancer
核心洞察
Researchers developed bovine serum albumin (搜索) (BSA (搜索))-encapsulated morin hydrate (搜索) nanoparticles (MHNPs) with 90 nm size and 71.66% drug entrapment efficiency to overcome the poor bioavailability of this natural anticancer compound.
The nanoformulation demonstrated superior antioxidant activity and enhanced cytotoxicity against HCT116 (搜索) colorectal cancer (搜索) cells compared to free morin hydrate (搜索), with IC50 values reduced from 140 μg/mL to 100 μg/mL.
Molecular docking and dynamics simulations revealed strong binding interactions between BSA (搜索) and morin hydrate (搜索) with a binding energy of -8.4 kcal/mol, supporting sustained drug release over 24 hours.
Researchers at Central University of Gujarat (搜索) have successfully developed bovine serum albumin (搜索) (BSA (搜索))-encapsulated nanoparticles containing morin hydrate (搜索), a natural flavonoid with anticancer properties, demonstrating enhanced therapeutic potential against colorectal cancer (搜索) cells. The study addresses critical limitations of morin hydrate including poor solubility, stability, and bioavailability that have hindered its clinical application.
Nanoparticle Development and Characterization
The research team employed a desolvation method to synthesize BSA (搜索)-encapsulated morin hydrate (搜索) nanoparticles (MHNPs), achieving optimal formulation parameters with 100 mg BSA, 20 mg morin hydrate, and 150 μL crosslinker at pH 9. The resulting nanoparticles exhibited a mean size of 90 nm as determined by transmission electron microscopy, with a polydispersity index of 0.224 indicating uniform distribution.
Comprehensive characterization using X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR) confirmed successful encapsulation. The drug entrapment efficiency reached 71.66 ± 1.5% with a loading capacity of 10 ± 0.5%. Notably, XRD analysis revealed a complete transition of morin hydrate (搜索) from crystalline to amorphous form upon encapsulation, which is expected to enhance solubility and bioavailability.
Molecular Interactions and Stability
Molecular docking studies revealed strong binding affinity between BSA (搜索) and morin hydrate (搜索) with a binding energy of -8.4 kcal/mol. The interaction was stabilized through hydrogen bonding with amino acid residues LEU-112, ASP-111, and ARG-196, along with hydrophobic interactions involving PRO-110, ARG-144, and ARG-458 residues.
Molecular dynamics simulations conducted over 100 nanoseconds demonstrated structural stability of the BSA (搜索)-morin hydrate (搜索) complex, with a root-mean-square deviation value of 3.4 Å. Free energy binding calculations using the MM-PB(GB)SA approach yielded a highly favorable binding affinity (ΔG = -80.18 ± 0.19 kcal/mol), confirming the stability of the drug-protein complex.
Enhanced Drug Release and Bioactivity
The nanoformulation exhibited pH-responsive drug release characteristics crucial for targeted delivery. In simulated gastric fluid (pH 1.2), approximately 35% of the drug was released within 3 hours, while increasing the pH to 7.4 resulted in 90% release of total encapsulated morin hydrate (搜索) over 15 hours, with complete release achieved by 24 hours. This release pattern followed the Higuchi model, indicating diffusion-controlled release from the nanoparticle matrix.
Antioxidant activity assessment using the DPPH assay demonstrated that MHNPs exhibited significantly higher radical scavenging efficacy compared to free morin hydrate (搜索), reaching approximately 78% at 180 μg/mL concentration. This enhanced performance was attributed to improved solubility and consistent release provided by BSA (搜索) encapsulation.
Anticancer Efficacy Against Colorectal Cancer
In vitro cytotoxicity studies using HCT116 (搜索) colorectal cancer (搜索) cells revealed superior anticancer activity of MHNPs compared to free morin hydrate (搜索). The IC50 value was reduced from 140 μg/mL for free drug to 100 μg/mL for the nanoformulation after 24 hours of treatment, and further decreased to 80 μg/mL after 48 hours.
Apoptosis assays using acridine orange-ethidium bromide staining confirmed enhanced cell death induction by MHNPs. Colony formation assays demonstrated marked suppression of colony formation in cancer cells treated with MHNPs compared to pure morin hydrate (搜索), indicating superior antiproliferative activity.
Thermal Stability and Clinical Implications
Thermal analysis revealed significant improvement in the stability profile of encapsulated morin hydrate (搜索). DSC analysis showed a shift in the degradation temperature from 292°C for pure morin hydrate to 251.2°C for the nanoformulation, accompanied by reduced crystallinity. TGA results demonstrated enhanced thermal protection of morin hydrate within the nanoparticle matrix, with degradation onset shifting to higher temperatures (250°C-350°C) compared to free drug (200°C-250°C).
The research team noted that BSA (搜索) nanoparticles maintained their form and physical state even after numerous centrifugation and reconstitution cycles, with particle size and polydispersity index remaining consistent over 30 days of monitoring.
Future Therapeutic Applications
The study highlights the potential of BSA (搜索)-based nanocarriers for improving the therapeutic efficacy of phytochemicals in cancer treatment. The enhanced solubility, sustained release profile, and improved bioavailability of morin hydrate (搜索) through nanoencapsulation address key challenges in natural product drug development.
With colorectal cancer (搜索) burden expected to rise 60% by 2030, this nanoformulation approach offers a promising strategy for developing more effective treatments. The researchers suggest that future work should focus on in vivo studies and pharmacokinetic evaluations to further assess the clinical applicability of MHNPs in targeted drug delivery and therapeutic interventions.