Bioconjugation of trypsin onto gold nanoparticles: Effect of surface chemistry on bioactivity

In this content, a small molecular ligand of prostate specific membrane antigen (SMLP) conjugated poly (caprolactone) (PCL)-b-poly (ethylene glycol) (PEG) copolymers with different block lengths were synthesized to construct a satisfactory drug delivery system. Four different docetaxel-loaded polymeric micelles (DTX-PMs) were prepared by dialysis with particle sizes less than 60 nm as characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Optimization of the prepared micelles was conducted based on short-term stability and drug-loading content. The results showed that optimized systems were able to remain stable over 7 days. Compared with Taxotere, DTX-PMs with the same ratio of hydrophilic/hydrophobic chain length displayed similar sustained release behaviors. The cytotoxicity of the optimized targeted DTX-PCL12K-PEG5K-SMLP micelles (DTX-PMs2) and non-targeted DTX-PCL12K-mPEG5K micelles (DTX-PMs1) were evaluated by MTT assays using prostate specific membrane antigen (PSMA) positive prostate adenocarcinoma cells (LNCaP). The results showed that the targeted micelles had a much lower IC50 than their non-targeted counterparts (48 h: 0.87±0.27 vs 13.48±1.03 µg/ml; 72 h: 0.02±0.008 vs 1.35±0.54 µg/ml). In vitro cellular uptake of PMs2 showed 5-fold higher fluorescence intensity than that of PMs1 after 4 h incubation. According to these results, the novel nano-sized drug delivery system based on DTX-PCL-PEG-SMLP offers great promise for the treatment of prostatic cancer.

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“…The coupling efficiency with amine nucleophiles can be increased by the formation of an NHS ester intermediate [29].…”

Section: Resultsmentioning

confidence: 99%

PSMA Ligand Conjugated PCL-PEG Polymeric Micelles Targeted to Prostate Cancer Cells

et al. 2014

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“…In addition, other biomolecules such as proteins, peptides, polysaccharides, and nucleic acids, have been used to stabilize AuNPs using similar strategies with different linkers [79][80][81]. For example, Helmut et al conjugated AuNPs to trypsin-NH 2 via immobilization through 1-ethyl-3-(3-dimethylaminopropylcarbodiimide/N-hydroxysuccinimide (EDC/NHS) bioconjugation onto functional carboxylic AuNPs (AuNP-S-Spacer-COO -) to generate AuNPs-trypsin with an amide linkage [82]. In addition, Tao et al synthesized M2e-conjugated AuNPs via thiol-gold interactions, which could be lyophilized and stably re-suspended in water [83].…”

Section: Surface Chemistrymentioning

confidence: 99%

Biomimetic gold nanocomplexes for gene knockdown: Will gold deliver dividends for small interfering RNA nanomedicines?

et al. 2015

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KEYWORDS siRNA delivery, RNA interference (RNAi)-based therapeutics, multifunctional nanoparticles, nanotoxicity of gold nanoparticles ABSTRACT RNA interference (RNAi) effectors such as small interfering RNA (siRNA) and micro RNA (miRNA) can selectively downregulate any gene implicated in the pathology of a disease. Therefore, RNAi-based therapies have immense potential for the treatment of a wide range of diseases. However, pharmacokinetic and pharmacodynamic studies have revealed that these therapeutic agents have poor bioactivity due to a number of factors, including insufficient plasma drug levels, short plasma half-lives, renal clearance, and hepatic metabolism. Non-viral delivery may facilitate the clinical application of siRNA-based therapeutics by helping to overcome these barriers. Recently, the potential of gold nanoparticles (AuNPs) as multifunctional carriers for transporting drugs, proteins, and genetic materials has been demonstrated. In this review, some of the key properties of AuNPs relevant to siRNA delivery, such as physical properties and surface chemistry have been described. In addition, the ability of AuNP-based formulation strategies to successfully overcome delivery barriers associated with siRNA, and the potential for this material to translate into safe and effective nanomedicines are critically discussed.

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“…In addition, its relatively small size and well-characterized A c c e p t e d M a n u s c r i p t 4 three-dimensional structure make it a good candidate for an analysis of the interaction with Au NPs. Previous studies on the conjugation of trypsin with Au NPs have already presented some useful information about the binding mechanism, surface chemistry of nanoparticles and enzymatic activity [12][13][14]. We have previously reported a method of accurately determining the concentration of glutathione-stabilized Au NPs colloidal suspension [15], which enables us to obtain quantitative information on the interaction between Au NPs and trypsin.…”

Section: Introductionmentioning

confidence: 97%

Probing the binding of trypsin to glutathione-stabilized gold nanoparticles in aqueous solution

Wang

Liu

Yan

et al. 2015

Colloids and Surfaces B: Biointerfaces

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Bioconjugation of trypsin onto gold nanoparticles: Effect of surface chemistry on bioactivity

Cited by 68 publications

References 45 publications

PSMA Ligand Conjugated PCL-PEG Polymeric Micelles Targeted to Prostate Cancer Cells

PSMA Ligand Conjugated PCL-PEG Polymeric Micelles Targeted to Prostate Cancer Cells

Biomimetic gold nanocomplexes for gene knockdown: Will gold deliver dividends for small interfering RNA nanomedicines?

Probing the binding of trypsin to glutathione-stabilized gold nanoparticles in aqueous solution

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