Nanosonotechnology: the next challenge in cancer sonodynamic therapy

AbstractSonodynamic therapy (SDT) is a newly developed anticancer treatment where ultrasound is used to trigger the cytotoxic effect of chemical compounds, known as sonosensitizers. Although SDT is similar to photodynamic therapy (PDT), SDT activates the chemical compounds through energy transfer using ultrasound rather than light. Moreover, SDT can focus the ultrasound energy onto malignant sites situa\xadted deeply within tissues, thus overcoming the main drawback linked to the use of PDT. Several physical and chemical mechanisms underlying ultrasound bioeffects and anticancer SDT take advantage of the non-thermal effect of acoustic cavitation generated by selected pulsed or continuous ultrasound. As the physical-chemical structure of the sonosentizer is essential for the success of SDT, we believe that the different aspects related to nanotechnology in medicine might well be able to improve the triggering effect ultrasound has on sonosensitizing agents. Therefore, the aim of this review is to focus on how nanotechnology might improve this innovative anticancer therapeutic approach.</jats:p

Biomedical Applications of Reactive Oxygen Species Generation by Metal Nanoparticles

The design, synthesis and characterization of new nanomaterials represents one of the most dynamic and transversal aspects of nanotechnology applications in the biomedical field. New synthetic and engineering improvements allow the design of a wide range of biocompatible nanostructured materials (NSMs) and nanoparticles (NPs) which, with or without additional chemical and/or biomolecular surface modifications, are more frequently employed in applications for successful diagnostic, drug delivery and therapeutic procedures. Metal-based nanoparticles (MNPs) including metal NPs, metal oxide NPs, quantum dots (QDs) and magnetic NPs, thanks to their physical and chemical properties have gained much traction for their functional use in biomedicine. In this review it is highlighted how the generation of reactive oxygen species (ROS), which in many respects could be considered a negative aspect of the interaction of MNPs with biological matter, may be a surprising nanotechnology weapon. From the exchange of knowledge between branches such as materials science, nanotechnology, engineering, biochemistry and medicine, researchers and clinicians are setting and standardizing treatments by tuning ROS production to induce cancer or microbial cell death

Targeted treatment of folate receptor-positive platinum-resistant ovarian cancer and companion diagnostics, with specific focus on vintafolide and etarfolatide

Among the gynecological malignancies, ovarian cancer is the leading cause of mortality in developed countries. Treatment of ovarian cancer is based on surgery integrated with chemotherapy. Platinum-based drugs (cisplatin and carboplatin) comprise the core of first-line chemotherapy for patients with advanced ovarian cancer. Platinum-resistant ovarian cancer can be treated with cytotoxic chemotherapeutics such as paclitaxel, topotecan, PEGylated liposomal doxorubicin, or gemcitabine, but many patients eventually relapse on treatment. Targeted therapies based on agents specifically directed to overexpressed receptors, or to selected molecular targets, may be the future of clinical treatment. In this regard, overexpression of folate receptor-α on the surface of almost all epithelial ovarian cancers makes this receptor an excellent “tumor-associated antigen”. With appropriate use of spacers/linkers, folate-targeted drugs can be distributed within the body, where they preferentially bind to ovarian cancer cells and are released inside their target cells. Here they can exert their desired cytotoxic function. Based on this strategy, 12 years after it was first described, a folate-targeted vinblastine derivative has now reached Phase III clinical trials in ovarian cancer. This review examines the importance of folate targeting, the state of the art of a vinblastine folate-targeted agent (vintafolide) for treating platinum-resistant ovarian cancer, and its diagnostic companion (etarfolatide) as a prognostic agent. Etarfolatide is a valuable noninvasive diagnostic imaging agent with which to select ovarian cancer patient populations that may benefit from this specific targeted therapy

High energy shock waves and 5-aminolevulinic for sonodynamic therapy: effects in a syngeneic model of colon cancer

The cytotoxic effect of the natural porphyrin precursor 5-aminolevulinic acid (ALA) exposed to high energy shock waves (HESW) was investigated in vitro on DHD/K12/TRb rat colon cancer cells and in vivo on a syngeneic colon cancer model. In vitro, viable cell growth was determined by trypan blue exclusion assay and cell death was investigated by flow cytometry. ALA (50 μg/ml) and HESW (E1, EFD = 0.22 mJ/mm2, 1000 shots or E2, EFD = 0.88 mJ/mm2, 500 shots) showed a significant reduction of cancer cell proliferation at day 3 compared to cells exposed to ALA (p &lt; 0.01) or HESW (p &lt; 0.001) alone. An enhancement of necrotic and apoptotic cells was observed after combined treatment at day 1 with ALA and HESW E1 (a 3.1 and 6.4 fold increase vs ALA alone) or E2 (a 3.4 and 5.3 fold increase vs ALA alone). In vivo, apoptosis detection was carried out by TUNEL assay, the pro-apoptotic gene Bad and Bcl-2 mRNA expression was evaluated by quantitative SYBR Green real time RT-PCR and cleavage of poly(ADP-ribose)-polymerase (PARP) was investigated by Western Blotting. An enhancement of apoptosis was observed in tumour tissues after the combined treatment at day 1 with ALA (375 mg/kg i.v.) and HESW (E2) compared to that of ALA exposure alone with improved apoptotic index (a 2.0 fold increase), Bad enhanced mRNA expression (p &lt; 0.01), Bcl-2 decreased mRNA expression (p &lt; 0.05) and increased PARP cleavage. The interaction between HESW and ALA is then effective in inducing apoptosis on a syngeneic colon cancer model. </jats:p

Validation of the CAchexia SCOre (CASCO). Staging cancer patients: The use of miniCASCO as a simplified tool

The CAchexia SCOre (CASCO) was described as a tool for the staging of cachectic cancer patients. The aim of this study is to show the metric properties of CASCO in order to classify cachectic cancer patients into three different groups, which are associated with a numerical scoring. The final aim was to clinically validate CASCO for its use in the classification of cachectic cancer patients in clinical practice. We carried out a case -control study that enrolled prospectively 186 cancer patients and 95 age-matched controls. The score includes five components: (1) body weight loss and composition, (2) inflammation/metabolic disturbances/immunosuppression, (3) physical performance, (4) anorexia, and (5) quality of life. The present study provides clinical validation for the use of the score. In order to show the metric properties of CASCO, three different groups of cachectic cancer patients were established according to the results obtained with the statistical approach used: mild cachexia (15 â\u89¤ Ã\u97 â\u89¤ 28), moderate cachexia (29 â\u89¤ Ã\u97 â\u89¤ 46), and severe cachexia (47 â\u89¤ Ã\u97 â\u89¤ 100). In addition, a simplified version of CASCO, MiniCASCO (MCASCO), was also presented and it contributes as a valid and easy-to-use tool for cachexia staging. Significant statistically correlations were found between CASCO and other validated indexes such as Eastern Cooperative Oncology Group (ECOG) and the subjective diagnosis of cachexia by specialized oncologists. A very significant estimated correlation between CASCO and MCASCO was found that suggests that MCASCO might constitute an easy and valid tool for the staging of the cachectic cancer patients. CASCO and MCASCO provide a new tool for the quantitative staging of cachectic cancer patients with a clear advantage over previous classifications