Bioactive Glasses as Carriers of Cancer-Targeted Drugs: Challenges and Opportunities in Bone Cancer Treatment.

The treatment of bone cancer involves tumor resection followed by bone reconstruction of the defect caused by the tumor using biomaterials. Additionally, post-surgery protocols cover chemotherapy, radiotherapy, or drug administration, which are employed as adjuvant treatments to prevent tumor recurrence. In this work, we reviewed new strategies for bone cancer treatment based on bioactive glasses as carriers of cancer-targeted and other drugs that are intended for bone regeneration in conjunction with adjuvant treatments. Drugs used in combination with bioactive glasses can be classified into cancer-target, osteoclast-target, and new therapies (such as gene delivery and bioinorganic). Microparticulated, nanoparticulated, or mesoporous bioactive glasses have been used as drug-delivery systems. Additionally, surface modification through functionalization or the production of composites based on polymers and hydrogels has been employed to improve drug-release kinetics. Overall, although different drugs and drug delivery systems have been developed, there is still room for new studies involving kinase inhibitors or antibody-conjugated drugs, as these drugs have been poorly explored in combination with bioactive glasses.

Strategies for Cancer Treatment Based on Photonic Nanomedicine.

Traditional cancer treatments, such as surgery, radiotherapy, and chemotherapy, are still the most effective clinical practice options. However, these treatments may display moderate to severe side effects caused by their low temporal or spatial resolution. In this sense, photonic nanomedicine therapies have been arising as an alternative to traditional cancer treatments since they display more control of temporal and spatial resolution, thereby yielding fewer side effects. In this work, we reviewed the challenge of current cancer treatments, using the PubMed and Web of Science database, focusing on the advances of three prominent therapies approached by photonic nanomedicine: (i) photothermal therapy; (ii) photodynamic therapy; (iii) photoresponsive drug delivery systems. These photonic nanomedicines act on the cancer cells through different mechanisms, such as hyperthermic effect and delivery of chemotherapeutics and species that cause oxidative stress. Furthermore, we covered the recent advances in materials science applied in photonic nanomedicine, highlighting the main classes of materials used in each therapy, their applications in the context of cancer treatment, as well as their advantages, limitations, and future perspectives. Finally, although some photonic nanomedicines are undergoing clinical trials, their effectiveness in cancer treatment have already been highlighted by pre-clinical studies.

Sol-gel-derived 58S bioactive glass containing holmium aiming brachytherapy applications: A dissolution, bioactivity, and cytotoxicity study.

Bioactive glasses containing rare earth elements have been proposed as promising candidates for applications in brachytherapy of bone cancer. However, their safety relies on a proper dissolution to avoid radioactive materials in the human body, and desirable bioactive properties to regenerate the bone defect caused by the tumor. In this work, we proposed a new series of sol-gel-derived bioactive glasses containing holmium oxide, based on the system (100-x)(58SiO2-33CaO-9P2O5)-xHo2O3 (x = 1.25, 2.5 and 5 wt%). The glasses were characterized regarding their dissolution behavior, bioactivity, and cytotoxicity with pre-osteoblastic cells. Also, in the dissolution experiments, the Arrhenius and Eyring equations were used to obtain some thermodynamic properties of glass dissolution. The results evidenced that the addition of holmium ions in the glass structure decreased the energy barrier of hydrolysis reactions, which favors glass dissolution in an early-stage. However, in the long-term, the strength of Si-O-Ho bonds may be the cause of more stable dissolution. Besides, glasses containing holmium were as bioactive as the 58S bioactive glasses, a highly bioactive composition. Cytotoxicity results showed that all glasses were not cytotoxic, and the composition containing 5 wt.% of Ho2O3 enhanced cell viability. Finally, these results suggest that these glasses are suitable materials for brachytherapy applications due to their proper dissolution behavior, high bioactivity, and high cell viability.

Defining the molecular basis of tumor metabolism: a continuing challenge since Warburg's discovery.

Cancer cells are the product of genetic disorders that alter crucial intracellular signaling pathways associated with the regulation of cell survival, proliferation, differentiation and death mechanisms. The role of oncogene activation and tumor suppressor inhibition in the onset of cancer is well established. Traditional antitumor therapies target specific molecules, the action/expression of which is altered in cancer cells. However, since the physiology of normal cells involves the same signaling pathways that are disturbed in cancer cells, targeted therapies have to deal with side effects and multidrug resistance, the main causes of therapy failure. Since the pioneering work of Otto Warburg, over 80 years ago, the subversion of normal metabolism displayed by cancer cells has been highlighted by many studies. Recently, the study of tumor metabolism has received much attention because metabolic transformation is a crucial cancer hallmark and a direct consequence of disturbances in the activities of oncogenes and tumor suppressors. In this review we discuss tumor metabolism from the molecular perspective of oncogenes, tumor suppressors and protein signaling pathways relevant to metabolic transformation and tumorigenesis. We also identify the principal unanswered questions surrounding this issue and the attempts to relate these to their potential for future cancer treatment. As will be made clear, tumor metabolism is still only partly understood and the metabolic aspects of transformation constitute a major challenge for science. Nevertheless, cancer metabolism can be exploited to devise novel avenues for the rational treatment of this disease.

A promising action of riboflavin as a mediator of leukaemia cell death.

Besides having a pivotal biological function as a component of coenzymes, riboflavin appears a promissing antitumoral agent, but the underlying molecular mechanism remains unclear. In this work, we demonstrate that irradiated riboflavin, when applied at microM concentrations, induces an orderly sequence of signaling events finally leading to leukemia cell death. The molecular mechanism involved is dependent on the activation of caspase 8 caused by overexpression of Fas and FasL and also on mitochondrial amplification mechanisms, involving the stimulation of ceramide production by sphingomyelinase and ceramide synthase. The activation of this cascade led to an inhibition of mitogen activated protein kinases: JNK, MEK and ERK and survival mediators (PKB and IAP1), upregulation of the proapoptotic Bcl2 member Bax and downregulation of cell cycle progression regulators. Importantly, induction of apoptosis by irradiated riboflavin was leukaemia cell specific, as normal human lymphocytes did not respond to the compound with cell death. Our data indicate that riboflavin selectively activates Fas cascade and also constitutes a death receptor-engaged drug without harmful side effects in normal cells, bolstering the case for using this compound as a novel avenue for combating cancerous disease.