<p>Nanotechnology-Based Cisplatin Intracellular Delivery to Enhance Chemo-Sensitivity of Ovarian Cancer</p>

Abstract

Background: Platinum resistance is a major challenge in the management of ovarian cancer. Even low levels of acquired resistance at the cellular level lead to impaired response to cisplatin. In ovarian cancer intraperitoneal therapy, nanoparticle formulation can improve the cisplatin's pharmacokinetics and safety profile. Purpose: This work aimed to investigate the chemo-sensitivity of ovarian cancer SKOV3 cells upon short-term (72h) single treatment of cisplatin and cisplatin-loaded biodegradable nanoparticles (Cis-NP). The aim was then to determine the therapeutic properties of Cis-NP in vivo using a SKOV3-luc cells' xenograft model in mice. Methods: Cell cytotoxicity was assessed after the exposure of the cell culture to cisplatin or Cis-NP. The effect of treatments on EMT and CSC-like phenotype was studied by analyzing a panel of markers by flow cytometry. Intracellular platinum concentration was determined by inductively coupled plasma mass spectrometry (ICS-MS), and gene expression was evaluated by RNAseq analysis. The efficacy of intraperitoneal chemotherapy was evaluated in a SKOV3-luc cells' xenograft model in mice, through a combination of bioluminescence imaging, histological, and immunohistochemical analyses. Results: We observed in vitro that short-term treatment of cisplatin has a critical role in determining the potential induction of chemoresistance, and a nanotechnology-based drug delivery system can modulate it. The RNAseq analysis underlines a protective effect of nanoparticle system according to their ability to down-regulate several genes involved in chemoresistance, cell proliferation, and apoptosis. The highest intracellular platinum concentration obtained with Cis-NP treatment significantly improved the efficacy. Consistent with in vitro results, we found that Cis-NP treatment in vivo can significantly reduce tumor burden and aggressiveness compared to the free drug. Conclusion: Nanoparticle-mediated cisplatin delivery may serve as an intracellular depot impacting the cisplatin pharmacodynamic performance at cellular levels. These features may contribute to improving the drawbacks of conventional intraperitoneal therapy, and therefore will require further investigations in vivo.

Characterization of cisplatin-loaded chitosan nanoparticles and rituximab-linked surfaces as target-specific injectable nano-formulations for combating cancer

“…12 J). Recently, cisplatin and cisplatin-loaded NP were recently evaluated at 10.00 and 30.00 µM concentrations 49 . In their study, the morphology of cells treated with free cisplatin differed significantly from that of cells treated with cisplatin-loaded nanoparticles, with irregular forms, shrinkage, rounding, and detachment in the cisplatin-treated samples.…”

Cisplatin and Nano-particle Formulations of Cisplatin for Cancer Therapy: A Review

“…During his research, he found that microscopic images of dividing cells resembled the pattern of iron shavings exposed to a magnetic field and implied that an electrical area might also influence cell division. However, the studies reports had declared that platinum has no biological records, so they used platinum electrodes in a solution containing the standard laboratory bacteria "E. coil" in their experiment [25]. Further, the bacterial cells were immobile and did not divide as soon as the current was turned on, yet they continued to grow to 300 times their average length and began to separate again after the power was turned off.…”

Myocardial Cell Preservation from Potential Cardiotoxic Drugs: The Role of Nanotechnologies

“…Nanoliposomal formulations of cisplatin (termed lipoplatin) are part of standard oncological care, having passed the clinical trial phase, showing high dose accumulation in tumor sites, where they are thought to act as both chemotherapeutic and antiangiogenic agents [ 74 ]. Other strategies include gold nanocarriers and physical force methods such as magnetism, ultrasound, and heat [ 75 , 76 ]. Several studies were conducted for the development of cisplatin-loaded chitosan nanoparticles with successful results in terms of in vitro cytotoxicity and kinetics [ 77 , 78 , 79 ].…”