Naslov
Computational and experimental therapeutic efficacy analysis of andrographolide phospholipid complex self-assembled nanoparticles against Neuro2a cells

Autori
Mourya, Atul ; Pingle, Purva ; Babu, Chanti Katta ; Hartisree, Veerabroma ; Sainaga Jyothi, Vaskuri G.S. ; Novak, Jurica ; Pathak, Prateek ; Grishina, Maria ; Verma, Amita ; Kumar, Rahul ; Singh, Pankaj Kumar ; Khatri, Dharmendra Kumar ; Singh, Shashi Bala ; Madan, Jitender

Izvornik
Biochimica et Biophysica Acta (BBA) - General Subjects (0304-4165) 1867 (2023), 2; 130283, 12

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Andrographolide ; Neuroblastoma ; Complexation ; Molecular simulation ; Self-assembled nanoparticles

Sažetak
Background Neuroblastoma is one of the most common malignancies in childhood, accounts for approximately 7% of all malignancies. Andrographolide (AN) inhibits cancer cells progression via multiple pathways like cell cycle arrest, mitochondrial apoptosis, NF-κβ inhibition, and antiangiogenesis mechanism. Despite multiple advantages, application of AN is very limited due to its low aqueous solubility (6.39 ± 0.47 μg/mL), high lipophilicity (log P ~ 2.632 ± 0.135), and reduced stability owing to pH sensitive lactone ring. Objectives and results In present investigation, a molecular complex of AN with soya-L-α-phosphatidyl choline (SPC) was synthesized as ANSPC and characterized by FT-IR and1H NMR spectroscopy. Spectral and molecular simulation techniques confirmed the intermolecular interactions between the 14-OH group of AN and the N+(CH3)3part of SPC. In addition, molecular dynamics (MD) simulation was used to determine the degree of interaction between various proteins such as TNF-α, caspase-3, and Bcl-2. Later, ANSPC complex was transformed in to self-assembled soft nanoparticles of size 201.8 ± 1.48 nm with PDI of 0.092 ± 0.004 and zeta potential of −21.7 ± 0.85 mV. The IC50 offree AN (8.319 μg/mL) and the self-assembled soft ANSPC nanoparticles (3.406 μg/mL ~ 1.2 μg of AN) against Neuro2a cells was estimated with significant (P < 0.05) difference. Interestingly, the self-assembled soft ANSPC nanoparticles showed better endocytosis compared to free AN in Neuro2a cells. In-vitrobiological assays confirmed that self-assembled soft ANSPC nanoparticles induces apoptosis in Neuro2a cells by declining the MMP (Δψm) and increasing the ROS generation. Conclusion Self-assembled soft ANSPC nanoparticles warrant further in-depth antitumor study in xenograft model of neuroblastoma to establish the anticancer potential.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

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