Translational screening platform to evaluate chemotherapy in combination with focal therapy for retinoblastoma

Retinoblastoma is the most common pediatric eye cancer. It is currently treated with a limited number of drugs, adapted from other pediatric cancer treatments. Drug toxicity and relapse of the disease warrant new therapeutic strategies for these young patients. In this study, we developed a robust tumoroid-based platform to test chemotherapeutic agents in combination with focal therapy (thermotherapy) – a treatment option widely used in clinical practice – in accordance with clinically relevant trial protocols. The model consists of matrix-embedded tumoroids that retain retinoblastoma features and respond to repeated chemotherapeutic drug exposure similarly to advanced clinical cases. Moreover, the screening platform includes a diode laser (810 nm, 0.3 W) to selectively heat the tumoroids, combined with an on-line system to monitor the intratumoral and surrounding temperatures. This allows the reproduction of the clinical settings of thermotherapy and combined chemothermotherapy treatments. When testing the two main drugs currently used in clinics to treat retinoblastoma in our model, we observed results similar to those clinically obtained, validating the utility of the model. This screening platform is the first system to accurately reproduce clinically relevant treatment methods and should lead to the identification of more efficient drugs to treat retinoblastoma.     

Magnetic chitosan oligomer-sulfonate-stearic acid triple combination as cisplatin carrier for site-specific targeted on MCF-7 cancer cells: Preparation,characterization and in vitro experiments

In this study, a new amphiphilic target-specific adsorbent, chitosan oligomer-sulfonate-stearic acid triple combination (S-Cho-SA), and magnetic chitosan oligomer-sulfonate-stearic acid triple combination (M-S-Cho-SA) by oleic acid (OA)-modified Fe₃O₄ via hydrophobic interaction are fabricated. By modifying the nanoparticle surfaces and having the ability to magnetically allow the target region, these particles attract attention as important particles used in targeting mechanisms in cancer therapy. With magnetic nanoparticles and an external magnetic field, it is possible to transport therapeutic agents to the target site and keep them in the desired effect zone for a longer period of time. These new adsorbents are characterized by scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy, nuclear magnetic resonance (NMR), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), and thermogravimetric analysis (TG/DTA). After chemical characterization, it is complexed with cisplatin (CDDP). The magnetic adsorbents were loaded with high efficiency (>50%), and the release experiments exhibited that cisplatin is released more at pH 4.5 compared with pH 7.4 at 37°C. It showed better drug release results under a magnetic field for magnetic adsorbents (36% for pH 4.5 and 3.6% for pH 7.4). The biocompatibility of the prepared adsorbents was demonstrated via the XTT assay in MCF-7 cell lines. The results also exhibited that S-Cho-SA and M-S-Cho-SA were biocompatible, and free cisplatin and cisplatin-complexed adsorbents showed an antiproliferative effect. The results showed that these new cisplatin-loaded (M-S-Cho-SA) nanoparticles are good candidates for thermotherapy in cancer treatment in the future, as they can provide selectivity by site-specific targeting and hold onto an alternative magnetic field due to the magnetic nature of the nanoparticles.