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. 2022 Aug 19;12(36):23661-23674.
doi: 10.1039/d2ra03121c. eCollection 2022 Aug 16.

Anti-amyloidogenic property of gold nanoparticle decorated quercetin polymer nanorods in pH and temperature induced aggregation of lysozyme

Pranita Rananaware  1 , Parimal Pandit  1 , Seekha Naik  2 , Monalisa Mishra  2 , Rangappa S Keri  1 , Varsha P Brahmkhatri  1
Affiliations

Anti-amyloidogenic property of gold nanoparticle decorated quercetin polymer nanorods in pH and temperature induced aggregation of lysozyme

Pranita Rananaware et al. RSC Adv. .

Abstract

Quercetin is an abundant plant polyphenol effective against several diseases due to its antioxidant and anti-inflammatory activity. Herein, we report novel polymeric quercetin nanorods and the former decorated with gold nanoparticles for the first time. The prepared conjugates quercetin-polyvinylpyrrolidone (Q-PVP) and quercetin-polyvinylpyrrolidone-gold nanoparticles (Q-PVP-Au) were characterized by UV-visible spectroscopy, Fourier transform infrared, dynamic light scattering, and zeta potential measurements. The surface morphology of conjugates was analyzed by field emission scanning electron microscopy. These conjugates exhibit harmonized rod-like morphology with a narrow size distribution. Furthermore, the quercetin conjugates with nanorod morphology exhibited enhanced and prolonged drug release over a long period. The synthesized conjugates were investigated for lysozyme aggregation kinetics. ThT binding assay, fibril size measurement, and electron microscopy results revealed that conjugates could suppress fibrillogenesis in lysozyme. The highest amyloid aggregation inhibition activity (IC50) was obtained against Q-PVP and Q-PVP-Au at 32 μg mL-1 and 30 μg mL-1 respectively. The amyloid aggregate disintegration activity (DC50) obtained against Q-PVP and Q-PVP-Au was 27 μg mL-1 and 29 μg mL-1 respectively. The present quercetin conjugates exhibit enhanced bioavailability and stability. They were potent inhibitors of lysozyme aggregation that may find applications as a therapeutic agent in neurological diseases like Alzheimer's and Parkinson's.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Polymeric conjugates Q-PVP and Q-PVP-Au for inhibition of HEWL aggregation.
Scheme 2
Scheme 2. Schematic representation of the synthesis of Q-PVP and Q-PVP-Au conjugates.
Fig. 1
Fig. 1. (A) UV-Visible spectra of Q, AuNP, Q-PVP, and Q-PVP-Au; (B) Fourier transform infrared (FTIR) analysis for confirmation of functional groups in Q (Gray line), Q-PVP (blue line), Q-PVP-Au (green line), AuNP (pink line).
Fig. 2
Fig. 2. FE-SEM images of Q-PVP (a) After 60 min of synthesis; (b) after 90 min; (c) growth of Q-PVP nanorods was observed in 120 min; (d) Q-PVP nanorods were separated from clusters at 150 min; (e and f) the well-assembled Q-PVP nanorods formed in 180 min with the average diameter of 300–400 nm and length of 6–8 μm.
Fig. 3
Fig. 3. FE-SEM images of Q-PVP-Au (a) the big conglomerated flower like structure was observed in the presence of AuNP in 15 min; (b) growth of Q-PVP-Au nanorods was observed in 30 min. (c) After 60 min, nanorods were uniformly wrapped by AuNP; (d) well separated nanorods from clusters were observed at 90 min; (e and f) the well-assembled nanorods decorated with AuNP in Q-PVP-Au were observed at 120 min with an average diameter of 300–400 nm and length of 6–8 μm.
Fig. 4
Fig. 4. UV-visible spectra as a function of time for (A) Q-PVP; (B) Q-PVP-Au; (C) stability profiles of Q (purple) and Q-PVP (red) and Q-PVP-Au (green) monitored by UV-visible spectroscopy as a function of time; (D) controlled drug release profiles for Q-PVP and Q-PVP-Au at pH 7.4.
Fig. 5
Fig. 5. Morphological analysis of the HEWL aggregates. (a and b) FE-SEM images of HEWL aggregates with dense interlinked structure.
Fig. 6
Fig. 6. (A) Kinetic profiles of HEWL amyloid fibrils formed alone (control, black curve) and in the presence of different concentration of Q-PVP; (B) effect of Q-PVP-Au on HEWL aggregation measured using Th T assay; (C) effect of Q-PVP and (D) Q-PVP-Au on size of HEWL aggregates measured by DLS; (E) tyrosine fluorescence signal: effect of Q, PVP, AuNP, Q-PVP and Q-PNP-Au on tyrosine fluorescence signal quenching assay and (D) aggregate size measurement by DLS in presence of various nanoparticle.
Fig. 7
Fig. 7. (A) Effect of conjugates Q-PVP and Q-PVP-Au on aggregation kinetics of HEWL (B) Effect of Q-PVP and Q-PVP-Au on the amyloid aggregate dissolution kinetics of HEWL. The measurements were normalized to the intensity of untreated HEWL amyloid fibrils (taken as 100%).
Fig. 8
Fig. 8. SEM images for HEWL aggregation kinetics: (a) HEWL showing aggregation, whereas (b) HEWL with the Q-PVP and (c) Q-PVP-Au conjugates do not exhibit any aggregation upon incubation at 65 °C for 24 h. (d–f) SEM images for HEWL dissolution kinetics. (d) Already formed aggregates of HEWL were incubated with PVP-Q and PVP-Q-Au conjugates (e and f) at 65 °C for 24 h, and dissolution of the aggregates can be seen in the SEM images.
Fig. 9
Fig. 9. Morphological analysis of the HEWL aggregates. (a and b) AFM images of HEWL aggregates with dense interlinked fibrillar aggregates and (c and d) AFM images of HEWL amyloid aggregation in the presence of Q-PVP-Au. The concentration of conjugates was 22 μg mL−1.
Scheme 3
Scheme 3. Q-PVP, and Q-PVP-Au conjugates for inhibition of HEWL aggregation.
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