|Wednesday, July 20
Neurofilament Peptide-Biotin (NFL) gold (III)- complex bioconjugates: from Chemical Design to interaction with pancreatic (PDAC) cancer cells for Nanomedicine Applications
* Celia Arib, Laboratory CSPBAT, France
Recently Dr. Joël Eyer and his team have discovered the sequences named «Tubulin Binding Sites », TBS, located along the intermediate filaments which are able to bind with free tubulin. They have then revealed a peptid, NFL-TBS.40-63 (NeuroFilament Low subunit-Tubulin Binding Site 40-63), which can enter and interect specifically in different glioblastoma cell lines (mouse, rat, human and canine) . In this study, a new methodology was demonstrated to synthesize hybrid gold nanoparticles of interest in nanomedicine and their use against cancer cells. Gold (HAuCl4) is chelated with a peptide NFL-TBS.40-63 and stabilized with dicarboxylic acid terminated polyethylene glycol (PEG). The interactions between the peptide ions, PEG diacid (PEG) and Au (III) form a hybrid nanocarrier called NFL-BIOT IN-PEG-AuNPs . These new nano-objects were characterized by different analytical techniques : Raman, UV-visible spectroscopy, size and zeta potential measurements of the nanoparticles and transmission electron microscopy. After the development of NFL-BIOT IN-PEG-AuNPs) for cytotoxicity studies, these nanoparticles were tested on Mia PaCa-2 cell line (Pancreatic cancer cells). Studies of mitochondrial activities, cell internalization and phototherapy showed the efficiency of these nanoparticles. The results show the efficiency therapeutic of NFL-BIOT when it is complexed with Au. In vivo studies for the therapeutic efficiency of these nanoparticles were evaluated on mice induced by Mia PaCa-2. The results show that NFL-BIOT IN-PEG-AuNPs decrease the tumor growth without effects on the body weight of mice with an excellent anti-angiogenic effects. The cytokines levels were detected in order to evaluate the behaviour of serum inflammatory factors and the power of BIOT-NFL-PEG-AuNPs to boost immunitary system. The goal of this study is to develop an innovative agent to target and destroy pancreatic cancer cells which is proved by in vivo preclinical studies.
Synthesis of gold-based particles designed for combining radiosensitization and chemotherapy
* Chahrazad Benbalit, UTINAM UMR 6213 , France
Despite the emergence of new treatments, some cancers still have a poor prognosis. Nanomedicine represents a promising approach for both the early diagnosis and the therapy of cancers. Gold nanoparticles (NPs) were designed as radiosensitizing agent to enhance the safety and the efficacy of the radiotherapy. In this context, gadolinium chelate-coated gold NPs (Au@TADOTAGA(Gd)) have been developed for image-guided radiotherapy. These multifunctional NPs (core size: 2-3 nm; hydrodynamic diameter: 6-10 nm) behave both as positive contrast agents for MRI and as radiosensitizing agents for improving the effect of radiotherapy. The combination of imaging and therapy confers to Au@TADOTAGA(Gd) a high potential for image-guided radiotherapy1. But their potential is probably under exploited owing to a too rapid renal clearance. Their efficacy previously demonstrated in preclinical models is expected to be improved by increasing plasma half-life and retention time in tumor. Long-circulating properties would facilitate the accumulation in the tumor microenvironment by EPR effect. To improve the pharmacokinetic properties of gold nanoparticles, they were encapsulated using an original process in a larger biodegradable matrix of poly- (lactic-co-glycolic acid) (PLGA). This strategy was designed to postpone the renal excretion. A polycation, the polyethyleneimine (PEI), was used to electrostatically entrap gold nanoparticles in biodegradable PLGA particles. The size of nanocarriers was adjustable between 100 nm and 160 nm. The encapsulation yield ranged from 70% to 90%. After intravenous injection in healthy rat, the gold NPs concentration in the blood was tremendously increased within the first hour when encapsulated in PLGA matrix in comparison to unencapsulated NPs. The very low gold content in the kidney tissue at 24h post-injection, suggested a postponed renal clearance. T1-weighted magnetic resonance imaging showed that the PLGA shell did not alter the imaging contrast agent properties of gadolinium entrapped in the organic shell onto the gold NPs2. Moreover, the encapsulation of the gold NPs led after intratumoral injection to a better retention of the gold NPs in the solid tumor in comparison to free gold NPs. In addition to increase the vascular residence and the retention time of the gadolinium chelate-coated gold NPs, the encapsulation in PLGA exhibits another attractive asset. The interest for Au-PLGA is indeed strengthened by the possibility to co-encapsulate the gold NPs with hydrophobic anticancer agent (paclitaxel). The resulting NPs are expected to combine MRI, radiotherapy, chemotherapy, and higher circulation time for a greater efficiency in the cancer treatment. References  Laurent, G. et al. Nanoscale 8, 12054 (2016).  Laurent, G. et al. Colloids and Surfaces B Biointerfaces 205, 111875 (2021).
CTL-doxorubicin (DOX)-gold complex nanoparticles (DOX-AuGCs): from synthesis to enhancement of therapeutic effect on liver cancer model
8. Biomedical applications of gold: in vivo applications and technologies, injectable nanoparticles and pharmacology
* Qiqian Liu, CSPBAT laboratory , France
Recently, nanomedicine has led to engineered tunable devices capable to solve unsatisfied issues in the healthcare worldwide. One of the most investigated applications of nanomedicine is the treatment of cancer through the targeted destruction of cancer cells and tumors 1,2. Among tumors, hepatic cancer is one of the most commonly occurring tumors. There are approximately 800000 new cases every year worldwide. With respect to common drug therapies, target cancer approaches have recently paved the way for improved patient outcomes. This strategy is based on the principle that specific interactions occur between the tumor and anti-cancer agents 3,4. In this work, a rapid way to conceive doxorubicin (DOX) hybrid gold nanoparticles have been brought back, in which DOX and Au (III) ions were complexed with a hydrochloride-lactose-modified chitosan, named CTL and dicarboxylic acid-terminated polyethylene-glycol (PEG), leading to hybrid polymer-sugar-metal nanoparticles (DOX–AuGSs). All formulations were assessed by spectroscopic techniques (Raman and UV-Vis) and transmission electron microscopy (TEM). To estimate the therapeutic effect of DOX–AuGSs in liver cancer, murine HepG2 cells were used to induce a hepatic carcinoma model in nude mice. The survival time of the tumor-bearing mice, body weight and tumor volume were measured and recorded. The cytokines were used to detect the serum inflammatory factors, and the blood cell analyzer was used to determine the blood cell content of different groups of nude mice. The outcomes demonstrate that DOX–AuGCs significantly suppressed the tumor growth derived from human HepG2 injection and reduce the tumor index without affecting the body weight of mice. Moreover, DOX–AuGCs significantly reduced the serum levels of cytokines IL-6, TNF-α and IL-12 P70. Finally, a histological analysis of the heart tissue sections indicated that DOX–AuGCs significantly reduce the chronic myocardial toxicity of DOX during the period of treatment.