Development of multifunctional Gold Core Silica Shell nanomedicines for the immune/chemo/photothermal therapy of breast cancer

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

Publication . Figueiredo, André Q.; Rodrigues, Ana Carolina Félix; Fernandes, Natanael; Correia, I.J.; Moreira, André F.

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.

2023-09-08Journal article

Embargoed access

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

Publication . Guimarães, Rafaela; Rodrigues, Ana Carolina Félix; Fernandes, Natanael; Diogo, Duarte de Melo; Ferreira, Paula; Correia, I.J.; Moreira, André F.

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. Otherwise, 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 AuMSSTPANIS 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.

2021-03-20Journal article

Open access

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

Publication . Rodrigues, Ana Carolina Félix; Fernandes, Natanael; Diogo, Duarte de Melo; Correia, I.J.; Moreira, André F.

Cancer nanomedicines are designed to encapsulate different therapeuticagents, prevent their premature release, and deliver them specifically tocancer cells, due to their ability to preferentially accumulate in tumor tissue.However, after intravenous administration, nanoparticles immediatelyinteract with biological components that facilitate their recognition by theimmune system, being rapidly removed from circulation. Reports show thatless than 1% of the administered nanoparticles effectively reach the tumorsite. This suboptimal pharmacokinetic profile is pointed out as one of themain factors for the nanoparticles’ suboptimal therapeutic effectiveness andpoor translation to the clinic. Therefore, an extended blood circulation timemay be crucial to increase the nanoparticles’ chances of being accumulated inthe tumor and promote a site-specific delivery of therapeutic agents. For thatpurpose, the understanding of the forces that govern the nanoparticles’interaction with biological components and the impact of the physicochemicalproperties on the in vivo fate will allow the development of novel and moreeffective nanomedicines. Therefore, in this review, the nano–bio interactionsare summarized. Moreover, the application of cell-derived vesicles forextending the blood circulation time and tumor accumulation is reviewed,focusing on the advantages and shortcomings of each cell source.

2022-10-17Journal article

Open access

Red blood cell membrane-camouflaged gold-core silica shell nanorods for cancer drug delivery and photothermal therapy

Publication . Rodrigues, Ana Carolina F.; Correia, I.J.; Moreira, André F.

Gold core mesoporous silica shell (AuMSS) nanorods are multifunctional nanomedicines that can act simultaneously as photothermal, drug delivery, and bioimaging agents. Nevertheless, it is reported that once administrated, nanoparticles can be coated with blood proteins, forming a protein corona, that directly impacts on nanomedicines’ circulation time, biodistribution, and therapeutic performance. Therefore, it become crucial to develop novel alternatives to improve nanoparticles’ half-life in the bloodstream. In this work, Polyethylenimine (PEI) and Red blood cells (RBC)-derived membranes were combined for the first time to functionalize AuMSS nanorods and simultaneously load acridine orange (AO). The obtained results revealed that the RBC 41 derived membranes promoted the neutralization of the AuMSS’ surface charge and consequently improved the colloidal stability and biocompatibility of the nanocarriers. Indeed, the in vitro data revealed that PEI/RBC-derived membranes’ functionalization also improved the nanoparticles’ cellular internalization and was capable of mitigating the hemolytic effects of AuMSS and AuMSS/PEI nanorods. In turn, the combinatorial chemo-photothermal therapy mediated by AuMSS/PEI/RBC_AO nanorods was able to completely eliminate HeLa cells, contrasting with the less efficient standalone therapies. Such data reinforce the potential of AuMSS nanomaterials to act simultaneously as photothermal and chemotherapeutic agents.

2024-03-15Journal article

Open access

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

Publication . Rodrigues, Ana Carolina Félix; Fernandes, Natanael; Diogo, Duarte de Melo; Ferreira, Paula; Correia, I.J.; Moreira, André

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.

2021-12-02Journal article

Open access