IR780 loaded gelatin-PEG coated gold core silica shell nanorods for cancer-targeted photothermal/photodynamic therapy.

Gold core silica shell (AuMSS) nanorods present excellent physicochemical properties that allow their application as photothermal and drug delivery agents. Herein, AuMSS nanorods were dual-functionalized with Polyethylene glycol methyl ether (PEG-CH3 ) and Gelatin (GEL) to enhance both the colloidal stability and uptake by HeLa cancer cells. Additionally, the AuMSS nanorods were combined for the first time with IR780 (a heptamethine cyanine molecule) and its photothermal and photodynamic capacities were determined. The obtained results reveal that the encapsulation of IR780 (65 µg per AuMSS mg) increases the photothermal conversion efficiency of AuMSS nanorods by 10%, and this enhanced heat generation was maintained even after three irradiation cycles with a NIR (808 nm) laser. Moreover, the IR780-loaded AuMSS/T-PEG-CH3 /T-GEL presented ≈2-times higher uptake in HeLa cells, when compared to the non-coated counterparts, and successfully mediated the light-triggered generation of reactive oxygen species. Overall, the combination of photodynamic and photothermal therapy mediated by IR780-loaded AuMSS/T-PEG-CH3 /T-GEL nanorods effectively promoted the ablation of HeLa cancer cells.

In situ formation of alginic acid-gold nanohybrids for application in cancer photothermal therapy.

Gold-based nanoparticles present excellent optical properties that propelled their widespread application in biomedicine, from bioimaging to photothermal applications. Nevertheless, commonly employed manufacturing methods for gold-based nanoparticles require long periods and laborious protocols that reduce cost-effectiveness and scalability. Herein, a novel methodology was used for producing gold-alginic acid nanohybrids (Au-Alg-NH) with photothermal capabilities. This was accomplished by promoting the in situ reduction and nucleation of gold ions throughout a matrix of alginic acid by using ascorbic acid. The results obtained reveal that the Au-Alg-NHs present a uniform size distribution and a spike-like shape. Moreover, the nanomaterials were capable to mediate a temperature increase of ≈11°C in response to the irradiation with a near-infrared region (NIR) laser (808 nm, 1.7 W cm-2 ). The in vitro assays showed that Au-Alg-NHs were able to perform a NIR light-triggered ablation of cancer cells (MCF-7), being observed a reduction in the cell viability to ≈27%. Therefore, the results demonstrate that this novel methodology holds the potential for producing Au-Alg-NH with photothermal capacity and higher translatability to the clinical practice, namely for cancer therapy.

TCP Doped with Metal Ions Reinforced with Tetragonal and Cubic Zirconia.

Ceramic biocomposites based on bioactive tricalcium phosphate doped with metal ions are a strategy for obtaining good biomimetics for human bone composition. Manufacturing with PMMA porogen also induces bone-like porosity morphology. The poor strength of tricalcium phosphate can be overcomed by designing ceramic composites reinforced with tetragonal and cubic zirconia. In this work, five different bioceramic composites were manufactured without and with induced porosity and their physical, mechanical, microstructural, and biological properties were studied. With the addition of tetragonal and cubic zirconia, an improvement in strength of 22% and 55%, respectively, was obtained, corresponding to up to 20.7 MPa. PMMA was suitable for adding porosity, up to 30%, with interconnectivity while an excellent hOB cellular viability was achieved for all biocomposites.

Cell-Derived Vesicles for Nanoparticles' Coating: Biomimetic Approaches for Enhanced Blood Circulation and Cancer Therapy.

Cancer nanomedicines are designed to encapsulate different therapeutic agents, prevent their premature release, and deliver them specifically to cancer cells, due to their ability to preferentially accumulate in tumor tissue. However, after intravenous administration, nanoparticles immediately interact with biological components that facilitate their recognition by the immune system, being rapidly removed from circulation. Reports show that less than 1% of the administered nanoparticles effectively reach the tumor site. This suboptimal pharmacokinetic profile is pointed out as one of the main factors for the nanoparticles' suboptimal therapeutic effectiveness and poor translation to the clinic. Therefore, an extended blood circulation time may be crucial to increase the nanoparticles' chances of being accumulated in the tumor and promote a site-specific delivery of therapeutic agents. For that purpose, the understanding of the forces that govern the nanoparticles' interaction with biological components and the impact of the physicochemical properties on the in vivo fate will allow the development of novel and more effective nanomedicines. Therefore, in this review, the nano-bio interactions are summarized. Moreover, the application of cell-derived vesicles for extending the blood circulation time and tumor accumulation is reviewed, focusing on the advantages and shortcomings of each cell source.

Metal-Polymer Nanoconjugates Application in Cancer Imaging and Therapy.

Metallic-based nanoparticles present a unique set of physicochemical properties that support their application in different fields, such as electronics, medical diagnostics, and therapeutics. Particularly, in cancer therapy, the plasmonic resonance, magnetic behavior, X-ray attenuation, and radical oxygen species generation capacity displayed by metallic nanoparticles make them highly promising theragnostic solutions. Nevertheless, metallic-based nanoparticles are often associated with some toxicological issues, lack of colloidal stability, and establishment of off-target interactions. Therefore, researchers have been exploiting the combination of metallic nanoparticles with other materials, inorganic (e.g., silica) and/or organic (e.g., polymers). In terms of biological performance, metal-polymer conjugation can be advantageous for improving biocompatibility, colloidal stability, and tumor specificity. In this review, the application of metallic-polymer nanoconjugates/nanohybrids as a multifunctional all-in-one solution for cancer therapy will be summarized, focusing on the physicochemical properties that make metallic nanomaterials capable of acting as imaging and/or therapeutic agents. Then, an overview of the main advantages of metal-polymer conjugation as well as the most common structural arrangements will be provided. Moreover, the application of metallic-polymer nanoconjugates/nanohybrids made of gold, iron, copper, and other metals in cancer therapy will be discussed, in addition to an outlook of the current solution in clinical trials.

Optimization of the GSH-Mediated Formation of Mesoporous Silica-Coated Gold Nanoclusters for NIR Light-Triggered Photothermal Applications.

Cancer light-triggered hyperthermia mediated by nanomaterials aims to eliminate cancer cells by inducing localized temperature increases to values superior to 42 °C, upon irradiation with a laser. Among the different nanomaterials with photothermal capacity, the gold-based nanoparticles have been widely studied due to their structural plasticity and advantageous physicochemical properties. Herein, a novel and straightforward methodology was developed to produce gold nanoclusters coated with mesoporous silica (AuMSS), using glutathione (GSH) to mediate the formation of the gold clusters. The obtained results revealed that GSH is capable of triggering and control the aggregation of gold nanospheres, which enhanced the absorption of radiation in the NIR region of the spectra. Moreover, the produced AuMSS nanoclusters mediated a maximum temperature increase of 20 °C and were able to encapsulate a drug model (acridine orange). In addition, these AuMSS nanoclusters were also biocompatible with both healthy (fibroblasts) and carcinogenic (cervical cancer) cells, at a maximum tested concentration of 200 µg/mL. Nevertheless, the AuMSS nanoclusters' NIR light-triggered heat generation successfully reduced the viability of cervical cancer cells by about 80%. This confirms the potential of the AuMSS nanoclusters to be applied in cancer therapy, namely as theragnostic agents.

HA/PEI-coated acridine orange-loaded gold-core silica shell nanorods for cancer-targeted photothermal and chemotherapy.

Aims: To develop a tumor-targeted chemo-photothermal nanomedicine through the functionalization of acridine orange (AO)-loaded gold-core mesoporous silica shell (AuMSS) nanorods with polyethylenimine (PEI) and hyaluronic acid (HA). Methods: Functionalization of the AuMSS nanorods was achieved through the chemical linkage of PEI followed by electrostatic adsorption of HA. Results: HA functionalization improved AuMSS' cytocompatibility by decreasing blood hemolysis, and PEI-HA inclusion promoted a controlled and sustained AO release. In vitro assays revealed that HA functionalization increased the internalization of nanoparticles by human negroid cervix epithelioid carcinoma cancer (HeLa) cells, and the combinatorial treatment mediated by AuMSS/PEI/HA_AO nanorods presented an enhanced effect, with >95% of cellular death. Conclusion: AuMSS/PEI/HA_AO formulations can act as tumor-targeted chemo-photothermal nanomedicines for the combinatorial therapy of cervical cancer.

Combinatorial delivery of doxorubicin and acridine orange by gold core silica shell nanospheres functionalized with poly(ethylene glycol) and 4-methoxybenzamide for cancer targeted therapy.

Combinatorial therapies based on the simultaneous administration of multiple drugs can lead to synergistic effects, increasing the efficacy of the cancer therapy. However, it is crucial to develop new delivery systems that can increase the drugs' therapeutic selectivity and efficacy. Gold core silica shell (AuMSS) nanoparticles present physicochemical properties that allow their simultaneous application as drug delivery and imaging agents. Herein, poly(ethylene glycol) was modified with 4-methoxybenzamide and 3-(triethoxysilyl)propyl isocyanate (TPANIS) to create a novel surface functionalization capable of improving the colloidal stability and specificity of AuMSS nanospheres towards cancer cells. Moreover, a dual drug combination based on Doxorubicin (DOX) and Acridine orange (AO) was characterized and administered using the AuMSS-TPANIS nanospheres. The obtained results show that the DOX:AO drug combination can mediate a synergistic therapeutic effect in both HeLa and MCF-7 cells, particularly at the 2:1, 1:1, and 1:2 ratios. Additionally, the TPANIS functionalization increased the AuMSS nanospheres colloidal stability and selectivity towards MCF-7 cancer cells (overexpressing sigma receptors). Such also resulted in an enhanced cytotoxic effect against MCF-7 cells when administering the DOX:AO drug combination with the AuMSS-TPANIS nanospheres. Overall, the obtained results confirm the therapeutic potential of the DOX:AO drug combination as well as the targeting capacity of AuMSS-TPANIS, supporting its application in the cancer-targeted combinatorial chemotherapy.

Overview of the application of inorganic nanomaterials in cancer photothermal therapy.

Cancer photothermal therapy (PTT) has captured the attention of researchers worldwide due to its localized and trigger-activated therapeutic effect. In this field, nanomaterials capable of converting the energy of the irradiation light into heat have been showing promising results in several pre-clinical and clinical assays. Such a therapeutic modality takes advantage of the innate capacity of nanomaterials to accumulate in the tumor tissue and their capacity to interact with NIR laser irradiation to exert a therapeutic effect. Therefore, several nanostructures composed of different materials and organizations for mediating a photothermal effect have been developed. In this review, the most common inorganic nanomaterials, such as gold, carbon-based materials, tungsten, copper, molybdenum, and iron oxide, which have been explored for mediating a tumor-localized photothermal effect, are summarized. Moreover, the physicochemical parameters of nanoparticles that influence the PTT effectiveness are discussed and the recent clinical advances involving inorganic nanomaterial-mediated cancer photothermal therapy are also presented.