Bombesin Peptide Conjugated Water-Soluble Chitosan Gallate—A New Nanopharmaceutical Architecture for the Rapid One-Pot Synthesis of Prostate Tumor Targeted Gold Nanoparticles

Abstract

Purpose:We report herein bombesin peptide conjugated water-soluble chitosan gallate as a template for rapid one-pot synthesis of gold nanoparticles (AuNPs) with capabilities to target receptors on prostate cancer cells. Methods: Water-soluble chitosan (WCS), anchored with gallic acid (GA) and LyslLys3 (1,4,7,10-tetraazacyclo dodecane-1,4,7,10-tetraacetic acid) bombesin 1-14 (DBBN) peptide, provides a tumor targeting nanomedicine agent. WCS nanoplatforms provide attractive strategies with built-in capabilities to reduce gold (III) to gold nanoparticles with stabilizing and tumor-targeting capabilities. WCS-GA-DBBN encapsulation around gold nanoparticles affords optimum in vitro stability. Results:The DBBN content in the WCS-GA-DBBN sample was ~27%w/w. The antioxidant activities of WCS-GA and WCS-GA-DBBN nanocolloids were enhanced by 12 times as compared to the nascent WCS. AuNPs with a desirable hydrodynamic diameter range of 40-60 nm have been efficiently synthesized using WCS-GA and WCS-GA-DBBN platforms. The AuNPs were stable over 4 days after preparation and ~3 days after subjecting to all relevant biological fluids. The AuNPs capped with WCS-GA-DBBN peptide exhibited superior cellular internalization into prostate tumor (PC-3) cells with evidence of receptor mediated endocytosis. Conclusion:The AuNPs capped with WCS-GA-DBBN exhibited selective affinity toward prostate cancer cells. AuNPs conjugated with WCS-GA-DBBN serve as a new generation of theranostic agents for treating various neoplastic diseases, thus opening-up new applications in oncology.

Nanostrategies for Therapeutic and Diagnostic Targeting of Gastrin-Releasing Peptide Receptor

“…However, the reaction, for instance, in tetrahydrofuran (THF) or dimethylformamide (DMF) is also possible as shown by Du and Li [17] and Mansour et al [46], respectively. Nevertheless, with no carboxylic groups available on the surface of the nanoparticle, nanoparticle's surface, or no amine group available in the ligand, the other way around can be equally efficient [16,47]. Poly(amidoamine) (PAMAM) dendrimers were conjugated with DOTA-modified BBN using the amine group on the dendrimer and carboxylic group of the DOTA moiety [48,49].…”

“…This approach led to the successful targeting of GRPR-positive breast cancer and Ehrlich tumor cells [71][72][73]. [35] polymeric micelles glioma Coumarin-6 Camptothecin (CPT) [61] prostate cancer Monomethyl auristatin F (MMAF) [65] elastin-like micelles prostate cancer - [63] Docetaxel (DTX) [74] nanostructured lipid carriers lung cancer Doxorubicin (DOX) [17] solid lipid nanoparticles breast cancer Doxorubicin (DOX) [59] PLGA nanoparticles breast cancer Docetaxel (DTX) [14] prostate cancer Docetaxel (DTX) [75] gold nanoparticles cervical cancer RAF peptide analog (Ac-Cys-Ahx-RAF) [69] prostate cancer 99m Tc [24] 99m Tc, 177 Lu [31] - [76] Gallic acid (GA) [47] prostate cancer, colon cancer 68 Ga [25] gold nanorods breast cancer Photothermal therapy -use of NIR laser irradiation [39] prostate cancer Heat-labile cytotoxic free radical donor -AIPH [77] graphene oxide glioblastoma Magnetic targeting, doxorubicin (DOX), NIR laser irradiation…”

“…Upon 48 h incubation, the examined AuNPs-WSCS-DOTA-BBN particles showed half maximal inhibitory concentration (IC50) values of 65.89 and 60.73 μg/mL, respectively, against PC-3 and LNCaP cells (compared to IC50 for AuNPs-WSCS being over 100 μg/mL) without any drug loaded; they also remained stable in biological media and proved safe for healthy HAEC aortic endothelial cells. Follow-up studies by the same team explored AuNPs reduced in situ within WSCS anchored with gallic acid (GA) and conjugated with DOTA-BBN [47]. The AuNPs-WCS-GA-DOTA-BBN exhibited an increased internalization into PC-3 cells when compared with the GA-free (previous study) or BBNfree conjugates as well as 2.4-fold lower IC50 values (5.94 μg/mL vs 12.05 μg/mL) after 48 h in comparison to AuNPs-WCS-GA.…”

Nanostrategies for Therapeutic and Diagnostic Targeting of Gastrin-Releasing Peptide Receptor

“…Nevertheless, with no carboxylic groups available on the surface of the nanoparticle, or no amine group available in the ligand, the other way around can be equally efficient [ 20 , 51 ]. Poly(amidoamine) (PAMAM) dendrimers were conjugated with DOTA-modified BBN using the amine group on the dendrimer and carboxylic group of the DOTA moiety [ 52 , 53 ].…”

Synthesis of Copper Nanoparticles-polyvinylpyrrolidone Composite Materials Using Simultaneous Irradiation Process

“…Polymers containing reactive functions for providing strong complexation or coordination and electrostatic interaction with the metallic ions precursor and their nanoparticles have been considered as stabilizers for metallic nanoparticle synthesis. Chitosan and its derivatives (Tangthong et al, 2021a(Tangthong et al, , 2021b, silk fibroin peptide (Wongkrongsak, Tangthong, & Pasanphan, 2016), ascorbic acid (Ismail et al, 2019), polyvinyl alcohol (PVA) (Zhou et al, 2008) and polyvinyl pyrrolidone (PVP) (Misra, Biswal, Gupta, Sainis, & Sabharwal, 2012) have been used as polymer stabilizer for metallic NPs synthesis. PVP is an amorphous, hygroscopic synthetic polymer composed of linear 1-vinyl-2-pyrrolidinone function (Hiremath, Nuguru, & Agrahari, 2019).…”