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Background: Photodynamic therapy (PDT) is a therapeutic intervention that can be applied to cancer treatment. The interaction between a photosensitizer (PS), ideal wavelength radiation, and tissue molecular oxygen triggers a series of photochemical reactions responsible for producing reactive oxygen species. These highly reactive species can decrease proliferation and induce tumor cell death. The search for PS of natural origin extracted from plants becomes relevant, as they have photoactivation capacity, preferentially targeting tumor cells and because they do not present any or little toxicity to healthy cells. Objective: Our work aimed to carry out a qualitative systematic review to investigate the effects of curcumin (CUR), a molecule considered as PS of natural origin, on PDT, using red light or near-infrared radiation in tumor models. Methods: A systematic search was performed in three databases (PubMed, Scopus, and Web of Science) using the PICOT method, retrieving a total of 1,373 occurrences. At the end of the peer screening, 25 eligible articles were included in this systematic review using inclusion, exclusion, and eligibility criteria. Results: CUR, whether in its free state, associated with metal complexes or other PS and in a nanocarrier system, was considered a relevant PS for PDT using red light or near-infrared against tumoral models in vitro and in vivo, acting by increasing cytotoxicity, inhibiting proliferation, inducing cell death mainly by apoptosis, and changing oxidative parameters. Conclusion: The results found in this systematic review suggest the potential use of CUR as a PS of natural origin to be applied in PDT against many neoplasms, encouraging further search in PDT against cancer and serving as an investigative basis for upcoming pre-clinical and clinical applications.

Photodynamic therapy (PDT) is a potential therapeutic modality against cancer, resulting from the interaction of a photosensitizer (PS) and radiation that generates damage to tumor cells. The use of near-infrared radiation (IR-A) is relevant because presents recognized biological effects, such as antioxidant, neuroprotective and antitumor effects. Glioblastoma is the most aggressive central nervous system (CNS) neoplasm with high proliferation and tissue invasion capacity and is resistant to radio and chemotherapy. Here, we evaluated in vitro the possible interaction of temozolomide (TMZ) with IR-A in a glioblastoma cell line (C6) and in a human keratinocyte cell line (HaCat) how non-tumor cell model, in an attempt to search for a new treatment strategy. The effects of TMZ, IR-A and the interaction between TMZ and IR-A was evaluated by viability exclusion with trypan blue. To perform the interaction experiments, we have chosen 10 μM TMZ and 4.5 J/cm2 of IR-A. From this, we evaluated cytotoxicity, cell proliferation, intracellular reactive oxygen species levels (ROS), as well as the process of cell migration and the P-gp and MRP-1 activity. Cell death mainly due to apoptosis, followed by necrosis, decreased cell proliferation, increased ROS levels, decreased cell migration and decreased P-gp and MRP1 activity were observed only when there was interaction between TMZ and IR-A in the C6 cell line. The interaction between TMZ and IR-A was not able to affect cell proliferation in the HaCat non-tumor cell line. Our results suggest that this interaction could be a promising approach and that in the future may serve as an antitumor strategy for PDT application.

Cerebrovascular diseases are currently a major global health problem. Considering the limitations of current therapy, the search for new alternatives for the treatment of these diseases is necessary and, in this context, curcumin, a molecule that has neuroprotective properties already described in the literature. A limiting factor when considering therapies for the nervous tissue is the presence of the blood–brain barrier which stimulates the search for new drug delivery strategies. In this context, nanoencapsulation seems to be a promising alternative. In this work, we compared the protective effects of free and nanoemulsified curcumin after intracerebral haemorrhage induced by collagenase (ICH) in Wistar rats. Injury area, motor activity, oxidative stress in the brain and serum biochemical parameters were investigated. Two hours after surgery, the first dose was injected intraperitoneally, followed by 24 and 48 h administration. Behavioural analysis was performed through 3 different tests: open field, beam walking and foot fault (24, 48 and 72 h respectively). At the end of the recovering time (3 days after injury), the animals were euthanized and the brain (for analysis of injury area and oxidative stress), blood (for biochemical parameters), kidney and liver (for histopathological examination) were investigated. Curcumin nanoemulsion 30 mg/kg was able to improve behavioural recovery, reduce the size of the haematoma and attenuate the weight loss caused by ICH. In terms of oxidative parameters, we observed that curcumin nanoemulsion modulated antioxidant responses with therapeutic potential against ICH. Only discrete results in few parameters were found with free-curcumin in the same dose.

Rapanea ferruginea antioxidant and antitumoral properties were not explored before in literature. This study aimed to investigate these biological activities for the R. ferruginea leaf extract and correlate them with its phenolic content and influence in biological membrane dynamics. Thus, in this study, anti/pro-oxidative properties of R. ferruginea leaf extract by in vitro DPPH and TBARS assays, with respect to the free radical reducing potential and to its activity regarding membrane free radical-induced peroxidation, respectively. Furthermore, preliminary tests related to the extract effect on in vitro glioma cell viability were also performed. In parallel, the phenolic content was detected by HPLC-DAD and included syringic and trans-cinnamic acids, quercetrin, catechin, quercetin, and gallic acid. In an attempt to correlate the biological activity of R. ferruginea extract and its effect on membrane dynamics, the molecular interaction between the extract and a liposomal model with natural-sourced phospholipids was investigated. Location and changes in vibrational, rotational, and translational lipid motions, as well as in the phase state of liposomes, induced by R. ferruginea extract, were monitored by Fourier-transform infrared spectroscopy, nuclear magnetic resonance, differential scanning calorimetry, and UV-visible spectroscopy. In its free form, the extract showed promising in vitro antioxidant properties. Free-form extract (at 1000µ g/mL) exposure reduced glioma cell in vitro viability in 40%, as evidenced by MTT tests. Pro-oxidant behavior was observed when the extract was loaded into liposomes. A 70.8% cell viability reduction was achieved with 500 µg/mL of liposome-loaded extract. The compounds of R. ferruginea extract ordered liposome interface and disorder edits a polar region. Phenolic content, as well as membrane interaction and modulation may have an important role in the oxidative and antitumoral activities of the R. ferruginea leaf extract.

Monastrol is a small cell-permeable heterocyclic molecule that is recognized as an inhibitor of mitotic kinesin Eg5. Heterocyclic–fatty acid derivatives are a new class of compounds with a broad range of biological activities. This work describes a comparative study of the in vitro antitumoral activity of a series of new long-chain monastrol analogues against rat glioblastoma cells. The novel analogues C6-substituted monastrol and oxo-monastrol were synthesized via Biginelli multicomponent condensation of fatty β-ketoester in good yields using a simple approach catalyzed by nontoxic and free-metal sulfamic acid. Following synthesis, their in vitro antitumoral activities were investigated. Notably, all analogues tested were active against rat glioblastoma cells. Superior activity was observed by analogues derived from palmitic and stearic fatty acid chains; these compounds were the most potent molecules, showing 13-fold higher potency than monastrol with IC(50) values of 5.11 and 6.85 μM, respectively. These compounds could provide promising new lead derivatives for more potent antitumor drugs.

This work describes the synthesis of new long-chain fatty acid polyhydroquinoline derivatives (hybrid PHQ-fatty acids) using a Hantzsch four-component reaction without the use of metals and catalyzed by non-toxic acids. The PHQ-fatty acids were synthesized from fatty β-ketoesters in the presence of sulfamic acid (H2NSO3H) in good yields (70–81%). Following the synthesis, for the first time, the in vitro antiproliferative activity of a series of long-chain PHQ-fatty acids was investigated in a glioma cell line (C6 rat malignant GBM cell line). Notably, all of the tested compounds were active against this cell line. Superior activity was observed for PHQ with a hydroxyl group on the aromatic ring and a stearic fatty acid chain, reducing the cell viability by ca. 40% at 5 μM.

Regarding free genistein small delivery to the central nervous system, physico-chemical parameters of dimiristoylphosphatidylcholine liposome-loaded genistein were investigated, as well as its in vitro activity against the DPPH radical and glioma cells. Data obtained by UV–vis spectroscopy, Fourier Transform Infrared Spectroscopy, Nuclear Magnetic Resonance, Differential Scanning Calorimetry and Dynamic Light Scattering were used to characterize the liposomal system with respect to motion restriction, hydration degree, trans-gauche isomerization and phase state. In vitro antitumoral effects were monitored through conting and viability assays. Genistein hydroxyl group and lipid hydrogen bonds may have important role in dimiristoylphosphatidylcholine phosphate and choline motion restriction. Genistein-induced choline restriction may be also related to a decrease in the group rotation rate. Genistein: dimiristoylphosphatidylcholine system showed higher molecular package at the acyl chains region compaired to empty liposomes, and it may be related to a decrease in gauche bonds quantity and system size. Lipid acyl chain length seems to influence different genistein effects on membranes, due to the presence of gauche conformers. Genistein: dimiristoylphosphatidylcholine liposome was more efficient as DPPH reducting system than the free-Gen. Liposomal system, at genistein 100 μM, was so efficient as the correspondent free-form genistein, probably showing higher stability to cross the blood-brain barrier. Genistein and the lipid did not show an additive activity against glioma cells. Antioxidant and anti-glioma genistein-loaded liposome potential may be related to the isoflavone location and its restriction effect in the lipid molecular motion. Anti-glioma activity may also be related to a decrease of system size and trans-gauche isomerization.