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- Microneedle-based delivery devices for cancer therapy: a reviewPublication . Moreira, André; Rodrigues, Ana Carolina Félix; Jacinto, Telma A.; Miguel, Sónia; Costa, Elisabete; Correia, I.J.Macroscale delivery systems that can be locally implanted on the tumor tissue as well as avoid all the complications associated to the systemic delivery of therapeutics have captured researchers' attention, in recent years. Particularly, the microneedle-based devices can be used to efficiently deliver both small and macro-molecules, like chemotherapeutics, proteins, and genetic material, along with nanoparticle-based anticancer therapies. Such capacity prompted the application of microneedle devices for the development of new anticancer vaccines that can permeate the tumor tissue and simultaneously improve the effectiveness of therapeutic agents. Based on the promising results demonstrated by the microneedle systems in the local administration of anticancer therapeutics, this review summarizes the different microneedle formulations developed up to now aimed for application on cancer therapy (mphasizing those produced with polymers). Additionally, the microneedles' general properties, type of therapeutic approach and its main advantages are also highlighted.
- Desenvolvimento e Funcionalização de Nanopartículas de Ouro com Revestimento de Sílica para Aplicação na Terapia do CancroPublication . Jacinto, Telma Maria Andrade; Correia, Ilídio Joaquim Sobreira; Moreira, André Ferreira; Rodrigues, Ana Carolina FélixCancer is one of the leading causes of death in the worldwide population and recent data indicates that its incidence will continue to increase in the next years. On the other hand, the traditional treatments such as surgery, radiotherapy, and chemotherapy have low therapeutic efficacies and induce systemic toxicity. Such have prompted the development of new therapeutic approaches for cancer. In this area, the application of nanomaterials to mediate a photothermal effect (i.e. heat generation upon light irradiation) and consequently induce the death of cancer cells has gained a considerable recognition by researchers and health professionals. Among the various types of nanoparticles developed until now, gold coremesoporous silica coated nanoparticles (AuMSS) have excellent physicochemical and biological properties, which allow their application as photothermal agents and drug carriers. However, the application of these nanoparticles in cancer therapy is hindered by their reduced blood circulation time and poor specificity to the tumor tissue. Thus, the present dissertation aimed to develop a new surface functionalization for the rodshaped AuMSS nanoparticles based on biofunctional polymers, in order to increase its blood circulation time, internalization by the cancer cells, and ultimately increase the therapeutic effect. For this purpose, the rod-shaped AuMSS were chemically modified with different ratios (1:1 and 4:1) of D-a-Tocopherol polyethylene glycol 1000 succinate (TPGS) and Hyaluronic Acid (HA). HA was selected due to its specificity towards the CD44 receptors that are overexpressed in the cancer cells’ membrane. On the other hand, TPGS owing to its amphiphilic nature is able to increase the nanomaterials solubility, and consequently its colloidal stability that enhances the blood circulation time. The obtained results showed that the rod-shaped AuMSS’ functionalization neutralized the nanoparticles’ surface charge, from -28 ± 10 mV to -3 ± 5 mV and 11 ± 2 mV for AuMSS-TPGSHA (1:1) and (4:1), respectively, without compromising the nanomaterials’ size distribution or photothermal capacity. Moreover, the success of the polymers grafting to the nanoparticles was confirmed by Fourier Transform Infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). In vitro assays demonstrated the biocompatibility of all formulations at concentrations up to 200 µg / mL in both healthy (fibroblast) and cancerous (cervical cancer) cells. However, the functionalization with TPGS and HA has improved the nanomaterials’ hemocompatibility as well as their selectivity towards cervical cancer cells. Finally, the photothermal effect mediated by the rod-shaped AuMSS effectively induced the death of the cancer cells In summary, the results presented in this dissertation confirm the successful functionalization of the AuMSS with the TPGS and HA. Additionally, the AuMSSs’ potential to be applied in cancer photothermal therapy was also demonstrated.
- Development of gold-core silica shell nanospheres coated with poly-2-ethyl-oxazoline and β-cyclodextrin aimed for cancer therapyPublication . Reis, Ana Catarina Almeida; Rodrigues, Ana Carolina Félix; Moreira, André; Jacinto, Telma A.; Ferreira, Paula; Correia, I.J.Cancer is one of the major world public health problems and the currently available treatments are nonspecific and ineffective. This reality highlights the importance of developing novel therapeutic approaches. In this field, multifunctional nanomedicines have the potential to revolutionize the currently available treatments. These unique nanodevices can simultaneously act as therapeutic and imaging agents allowing the real-time monitoring of the nanoparticles biodistribution and the treatment outcome. Among the different nanoparticles, the gold-core silica shell (AuMSS) nanoparticles advantageous physicochemical and biological properties make them promising nanoplatforms for cancer therapy. Nevertheless, their successful application as an effective cancer nanomedicine is limited by the unfavorable pharmacokinetics and uncontrolled release of the therapeutic payloads. Herein, a new polymeric coating for AuMSS nanospheres was developed by combining different ratios (25/75, 50/50 and 75/25) of two materials, Poly-2-ethyl-2-oxazoline (PEOZ) and β-cyclodextrin (β-CD). The surface functionalization of AuMSS nanospheres led to a size increase and to the neutralization of the surface charge. On the other side, the nanoparticles biological performance was improved. The coated AuMSS nanospheres showed an increased cytocompatibility and internalization rate by the HeLa cancer cells. Overall, the obtained data confirm the successful modification of the AuMSS nanospheres with PEOZ and β-CD as well as their promising properties for being applied in cancer therapy.
- Hyaluronic acid and vitamin E polyethylene glycol succinate functionalized gold-core silica shell nanorods for cancer targeted photothermal therapyPublication . Jacinto, Telma A.; Rodrigues, Ana Carolina Félix; Moreira, André F.; Miguel, Sónia P.; Costa, Elisabete; Ferreira, Paula; Correia, I.J.Gold-core mesoporous silica shell (AuMSS) nanorods unique physicochemical properties makes them versatile and promising nanomedicines for cancer photothermal therapy. Nevertheless, these nanomaterials present a reduced half-life in the blood and poor specificity towards the tumor tissue. Herein, d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and Hyaluronic Acid (HA) were combined for the first time to improve the AuMSS nanorods biological performance. The obtained results revealed that AuMSS surface functionalization induced the surface charge neutralization, from -28 ± 10 mV to −3 ± 5 mV and −10 ± 4 mV for AuMSS-TPGS-HA (1:1) and (4:1) formulations, without impacting on nanomaterials’ photothermal capacity. Moreover, the AuMSS functionalization improved the nanomaterials hemocompatibility and selectivity towards the cancer cells, particularly in the AuMSS-TPGS-HA (4:1) formulation. Furthermore, both formulations were able to mediate an on-demand photothermal effect, that induced the HeLa cancer cells death, confirming its potential for being applied as targeted multifunctional theragnostic nanomedicines.
- Poly (vinyl alcohol)/chitosan layer-by-layer microneedles for cancer chemo-photothermal therapyPublication . Moreira, André F.; Rodrigues, Ana Carolina Félix; Jacinto, Telma A.; Miguel, Sónia P.; Costa, Elisabete; Correia, I.J.The combination of photothermal and chemo- therapies displays a high potential to increase the efficacy of the cancer treatments or even promote their eradication. In this study, the micromoulding and electrospraying techniques were combined to produce polyvinylpyrrolidone microneedles coated with chitosan and poly (vinyl alcohol) for mediating the delivery of doxorubicin and AuMSS nanorods (Dox@MicroN) to cancer cells. The microneedles' physicochemical characterization demonstrated that the electrospraying technique can be used to produce a layer-by-layer coating consisting of layers of doxorubicin-loaded chitosan and AuMSS enriched poly (vinyl alcohol). Further, the Dox@MicroN patches presented a good photothermal capacity leading to a temperature increase of 12 °C under near-infrared irradiation (808 nm, 1.7 W/cm-2 for 5 min), which in conjugation with the chitosan' pH sensitivity could be used to control the doxorubicin release. Moreover, the microneedles were able to penetrate the tumor-mimicking agarose gel and promote a layer dependent drug release. Additionally, the Dox@MicroN patches' capacity to simultaneously mediate the chemo- and photothermal-therapies rendered a superior cytotoxic effect against the cervical cancer cells. Overall, the Dox@MicroN patches demonstrated to be a simple macroscale delivery device that can be used to mediate the local administration of new drug-photothermal combinations, avoiding all the issues related to the systemic administration of anti-cancer therapeutics.
- Functionalization of AuMSS nanorods towards more effective cancer therapiesPublication . Rodrigues, Ana Carolina Félix; Jacinto, Telma A.; Moreira, André; Costa, Elisabete C.; Miguel, Sónia P.; Correia, I.J.The application of nanoparticles as selective drug delivery platforms arises as one the most promising therapeutic strategies in the biomedical field. Such systems can encapsulate drugs, prevent its premature degradation, transport and promote the drugs specific delivery to the target site. Among the different nanostructures, gold-core mesoporous silica shell (AuMSS) nanorods have been one of the most explored due to their unique physical and chemical properties. The mesoporous silica biocompatibility, high surface area that can be easily functionalized, tubular pores that can store the drugs, conjugated with the intrinsic capacity of gold nanorod to absorb near-infrared radiation, allows the combination of hyperthermia (i.e., photothermal effect) with drug delivery, making them a nanoplatforms with a huge potential for cancer therapy. Nevertheless, the successful application of AuMSS nanoparticles as an effective cancer nanomedicine is hindered by the uncontrolled release of the therapeutic payloads, limited blood circulation time and unfavorable pharmacokinetics. In this review, an overview of the modifications performed to improve the AuMSS nanorods application in nanomedicine is provided, highlighting the practical approaches that enhanced the AuMSS nanorods targeting, responsiveness to different stimuli, and blood circulation time. Further, the basics of AuMSS nanorods synthesis procedures, general properties, and its application in cancer therapy are also described.