Optimally biosynthesized, PEGylated gold nanoparticles functionalized with quercetin and camptothecin enhance potential anti-inflammatory, anti-cancer and anti-angiogenic activities

Priyadarshani S Sadalage,Ana Cláudia Santos,Kiran D Pawar,Shruti S Gavade,Reshma V Patil,Darshana V Havaldar

doi:10.1186/s12951-021-00836-1

Abstract

BackgroundThe development of nano delivery systems is rapidly emerging area of nanotechnology applications where nanomaterials (NMs) are employed to deliver therapeutic agents to specific site in a controlled manner. To accomplish this, green synthesis of NMs is widely explored as an eco-friendly method for the development of smart drug delivery system. In the recent times, use of green synthesized NMs, especially metallic NMs have fascinated the scientific community as they are excellent carriers for drugs. This work demonstrates optimized green, biogenic synthesis of gold nanoparticles (AuNPs) for functionalization with quercetin (QT) and camptothecin (CPT) to enhance potential anti-inflammatory, anti-cancer and anti-angiogenic activities of these drugs.ResultsGold nanoparticles were optimally synthesized in 8 min of reaction at 90 °C, pH 6, using 4 mM of HAuCl4 and 4:1 ratio of extract: HAuCl4. Among different capping agents tested, capping of AuNPs with polyethylene glycol 9000 (PG9) was found best suited prior to functionalization. PG9 capped AuNPs were optimally functionalized with QT in 1 h reaction at 70 °C, pH 7, using 1200 ppm of QT and 1:4 ratio of AuNPs-PG9:QT whereas, CPT was best functionalized at RT in 1 h, pH 12, AuNPs-PG9:CPT ratio of 1:1, and 0.5 mM of CPT. QT functionalized AuNPs showed good anti-cancer activity (IC50 687.44 µg/mL) against MCF-7 cell line whereas test of anti-inflammatory activity also showed excellent activity (IC50 287.177 mg/L). The CAM based assessment of anti-angiogenic activity of CPT functionalized AuNPs demonstrated the inhibition of blood vessel branching confirming the anti-angiogenic effect.ConclusionsThus, present study demonstrates that optimally synthesized biogenic AuNPs are best suited for the functionalization with drugs such as QT and CPT. The functionalization of these drugs with biogenic AuNPs enhances the potential anti-inflammatory, anti-cancer and anti-angiogenic activities of these drugs, therefore can be used in biomedical application.

Highlights

The development of nano delivery systems is rapidly emerging area of nanotechnology applications where nanomaterials (NMs) are employed to deliver therapeutic agents to specific site in a controlled manner
Since plants are available, safe to handle and consist of broad range of metabolites, they are preferred as sources of capping and reducing agents for biogenic synthesis [28]
The initial reaction between almond seed coat extract (ASCE) and HAuCl4 precursor solution at 90 °C for 10 min turned the reaction color from pale yellow to light purple and dark ruby red indicating the synthesis of AuNPs due to reduction of Elemental Gold (Au)+3 to Auo (Fig. 1a)

Summary

Introduction

The development of nano delivery systems is rapidly emerging area of nanotechnology applications where nanomaterials (NMs) are employed to deliver therapeutic agents to specific site in a controlled manner. Use of green synthesized NMs, especially metallic NMs have fascinated the scientific community as they are excellent carriers for drugs. This work demonstrates optimized green, biogenic synthesis of gold nanoparticles (AuNPs) for functionalization with quercetin (QT) and camptothecin (CPT) to enhance potential anti-inflammatory, anti-cancer and anti-angiogenic activities of these drugs. The synthesis and use of NMs, especially metallic NMs have fascinated the scientific community as they are an excellent carriers for drugs [8], and can be modified in various ways for the controlled release of therapeutic payload into the cells for targeted delivery [9, 10]. Properties of AuNPs such as biocompatibility and ease of surface functionalization make them suitable for biomedical imaging [14] and as carrier in targeted drug delivery systems [15]. The variety of organic ligands can be functionalized on the surface of AuNPs to enhance their properties [13]

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