João Conde

Universidade NOVA de Lisboa | NOVA · Faculty of Medical Sciences

Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential traject...

Differential expression of microRNAs (miRNAs) plays a role in many diseases, including cancer and cardio-vascular diseases. Potentially, miRNAs could be targeted with miRNA-therapeutics. Sustained delivery of these therapeutics remains challenging. This study couples miR-mimics to PEG-peptide gold nano-particles (AuNP) and loads these AuNP-miRNAs i...

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15–39 years) are lacking. To address this...

Importance: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. Objective: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic...

RNA-based therapeutics have shown tremendous promise in disease intervention at the genetic level, and some have been approved for clinical use, including the recent COVID-19 messenger RNA vaccines. The clinical success of RNA therapy is largely dependent on the use of chemical modification, ligand conjugation or non-viral nanoparticles to improve...

Bio-mimicking principles have recently been proposed for the surface functionalization of nanoparticles (NPs). Such a strategy is based on camouflaging the NP surface with functional biomembranes to render superior biocompatibility, interfacial features, immune evasion, and active targeting properties to nanomaterials. In this area of research, cel...

The deployment of structures that enable localized release of bioactive molecules can result in more efficacious treatment of disease and better integration of implantable bionic devices. The strategic design of a biopolymeric coating can be used to engineer the optimal release profile depending on the task at hand. As illustrative examples, here a...

Cancer nanotherapy suffers from low-yield delivery that is imposed by tumour pathophysiological barriers. Top-down drug delivery strategies, including exosomes and cell membrane-coated particles, can improve safety and efficacy owing to the innate biointerfacial properties of these platforms. Here, we discuss the technological challenges that need...

This protocol describes the synthesis and characterization of gold nanoparticle-based nanobeacons as a theranostic strategy for the recognition, detection, and inhibition of miRNA and mRNA. This system is designed for an in vitro evaluation of a sequence’s silencing potential and later used for cellular and in vivo gene silencing approaches using f...

Background: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods:...

Cancer is a major healthcare burden and cause of death worldwide, with an estimated 19.3 million new cancer cases and 10 million cancer deaths globally only in 2020. While several anticancer therapeutics are available to date, many of these still show low treatment efficacy and high off-target effects and adverse reactions. This prompts a serious n...

Nucleic acid-based therapy emerges as a powerful weapon for the treatment of tumors thanks to its direct, effective, and lasting therapeutic effect. Encouragingly, continuous nucleic acid-based drugs have been approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Despite the tremendous progress, there are few n...

Janus heterostructures based on bimetallic nanoparticles have emerged as effective radiosensitizers owing to their radiosensitization capabilities in cancer cells. In this context, this study aims at developing a novel bimetallic nanoradiosensitizer, Bi2S3-Fe3O4, to enhance tumor accumulation and promote radiation-induced DNA damage while reducing...

Despite the advantages of nanoscale materials compared to conventional therapeutic and diagnostic methods, challenges remain on their poor biocompatibility, rapid elimination from the blood circulation and cytotoxicity. Biomimetic approaches utilize natural cell membrane-derived nanovesicles to camouflage nanoparticles to circumvent the aforementio...

Background Colorectal cancer is the third leading cause of cancer deaths worldwide. Given the recent increasing trends in colorectal cancer incidence globally, up-to-date information on the colorectal cancer burden could guide screening, early detection, and treatment strategies, and help effectively allocate resources. We examined the temporal pat...

There is growing need for a safe, efficient, specific and non-pathogenic means for delivery of gene therapy materials. Nanomaterials for nucleic acid delivery offer an unprecedented opportunity to overcome these drawbacks; owing to their tunability with diverse physico-chemical properties, they can readily be functionalized with any type of biomole...

Cell‐to‐cell communication within the heterogeneous solid tumor environment plays a significant role in the uncontrolled metastasis of cancer. To inhibit the metastasis and growth of cancer cells, various chemically designed and biologically derived nanosized biomaterials have been applied for targeted cancer therapeutics applications. Over the yea...

Background Disability and mortality burden of non-communicable diseases (NCDs) have risen worldwide; however, the NCD burden among adolescents remains poorly described in the EU. Methods Estimates were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Causes of NCDs were analysed at three different levels o...

Gold Nanoparticles In article number 2102321 by Farzad Seidi, João Conde, Ali Sharafi, and co‐workers, in vivo X‐ray radiation using prodrug polymeric nanoconjugates encapsulating gold nanoparticles impair the proliferation of breast cancer cells, blocking the ability of a single cancer cell to grow into a colony, and therefore forming tumors.

An optimal radiosensitizer with improved tumor retention have an important effect in tumor radiation therapy. Herein, gold nanoparticles (Au NPs) and drug containing, mPEG-conjugated CUR (mPEG-CUR), self-assembled NPs (mPEG-CUR@Au) were developed and evaluated as a drug carrier and radiosensitizer in a breast cancer mice model. As a result, cancer...

Nanotechnology for healthcare is coming of age, but automating the design of composite materials poses unique challenges. Although machine learning is supporting groundbreaking discoveries in materials science, new initiatives leveraging learned patterns are required to fully realize the promise of nanodelivery systems and accelerate development pi...

The interest in nanomedicine for cancer theranostics has grown significantly over the past few decades. However, these nanomedicines need to overcome several physiological barriers intrinsic to the tumor microenvironment (TME) before reaching their target. Intrinsic tumor genetic/phenotypic variations, along with intratumor heterogeneity, provide d...

The use of computational tools to identify biological targets of natural products with anticancer properties and unknown modes of action is gaining momentum. We employed self-organizing maps to deconvolute the phenotypic effects of piperlongumine (PL) and establish a link to modulation of the human transient receptor potential vanilloid 2 (hTRPV2)...

The emergence of the new coronavirus 2019 (COVID-19) was first seen in December 2019, which has spread rapidly and become a global pandemic. The number of cases of COVID-19 and its associated mortality have raised serious concerns worldwide. Early diagnosis of viral infection undoubtedly allows rapid intervention, disease management, and substantia...

So far, near-infrared (NIR) light responsive nanostructures have been well-defined in cancer nanomedicine. However, poor penetration and retention in tumors are the limiting factors. Here, we report the ultrahigh penetration and retention of carbanosilica (graphene quantum dots, GQDs embedded mesoporous silica) in solid tumors. After NIR light expo...

Correction for ‘Revisiting gene delivery to the brain: silencing and editing’ by João Conniot et al. , Biomater. Sci. , 2021, DOI: 10.1039/D0BM01278C.

Since decades, conventional diagnosis and treatment strategies for cancer have been practiced widely despite their expensive and time-consuming process. These conventional contrast and therapeutic agents suffer from various side-effects such as low radiodensity and image resolution, rapid clearance, non-specific biodistribution, poor tumor accumula...

Polyurea oxide (PURO) biodendrimers are a class of dendrimers that can trigger osteogenic differentiation of human mesenchymal stem cells (hMSCs). PURO biodendrimers are prepared by simple, solventless oxidation of polyurea dendrimers using hydrogen peroxide as the oxidant in quantitative yield, retaining both biocompatibility (up to 10 mg/mL for h...

Neurodegenerative disorders, ischemic brain diseases, and brain tumors are debilitating diseases that severely impact one’s life and could possibly lead to their demise if left untreated. Many of these diseases do not respond to small molecule therapeutics and have no effective long-term therapy. Gene therapy offers the promise of treatment or even...

Although treating COVID-19 is shown to be challenging, NANOtechnology is around the corner to overcome potential drawbacks. The use of NANOtechnologies will definitely shape the worldwide approaches and tools to treat COVID-19. Here we highlight the importance of going NANO on the COVID-19 pandemic.

The caged fluorogenic near‐infrared probe tHCA is presented in the cover picture as a chained molecule. As demonstrated by G. J. L. Bernardes in their Research Article (DOI: 10.1002/anie.202008012), the activity of the probe can be restored by specific reaction with a tetrazine “key” in combination with single‐walled carbon nanotubes to recover the...

Die aktivierbare fluorogene Nahinfrarotsonde tHCA wird im Titelbild als kettenförmiges Molekül dargestellt. Wie G. J. L. Bernardes et al. in ihrem Forschungsartikel zeigen (DOI: 10.1002/ange.202008012), kann die Aktivität der Sonde durch spezifische Reaktion mit einem Tetrazin‐„Schlüssel“ in Kombination mit einwandigen Kohlenstoffnanoröhren wiederh...

Nanotechnology-based antimicrobial and antiviral formulations can prevent SARS-CoV-2 viral dissemination, and highly sensitive biosensors and detection platforms may contribute to the detection and diagnosis of COVID-19.

Developing a nanotheranostic agent with better image resolution and high accumulation into solid tumor microenvironment is a challenging task. Herein, we established a light mediated phototriggered strategy for enhanced tumor accumulation of nanohybrids. A multifunctional liposome based nanotheranostics loaded with gold nanoparticles (AuNPs) and em...

The bioorthogonal inverse‐electron‐demand Diels–Alder (IEDDA) cleavage reaction between tetrazine and trans‐cyclooctene (TCO) is a powerful way to control the release of bioactive agents and imaging probes. In this study, a pretargeted activation strategy using single‐walled carbon nanotubes (SWCNTs) that bear tetrazines (TZ@SWCNTs) and a TCO‐caged...

Pretarget then activate: Functionalization of single‐walled carbon nanotubes (SWCNTs) with tetrazines led to a stable and biocompatible material that undergoes a rapid inverse‐electron‐demand Diels–Alder reaction with trans‐cyclooctene caged molecules. This approach enables bioorthogonal activation of responsive drugs or probes in solid tumours in...

The ability to create ways to control drug activation at specific tissues while sparing healthy tissues remains a major challenge. The admin-istration of exogenous target-specific triggers offers the potential for traceless release of active drugs on tumor sites from antibody-drug conjugates (ADCs) and caged prodrugs. We have developed a metal-medi...

Given extensive reports of anticancer nanomedicines in preclinical studies, why is there such a paucity of clinical trials using these therapies? Nanotechnology can certainly deliver, but we need to tackle the limitations that are impeding the translation of nanomedicines into the clinic and start benefiting from their full potential.

In article number 1901101 by Natalie Artzi and co‐workers, dual‐sensitive nanogels rapidly dislodge the chemotherapy drug inside cancer cells through pH and redox sensitivities, enabling efficient cancer‐cell killing. Their incorporation into an injectable hydrogel, delivered to tumor‐adjacent areas, enables prolonged release of the nanogels, with...

Triple negative breast cancer patients remain with chemotherapy as their only viable therapeutic option. However, the toxicity of available anticancer drugs and their inefficient delivery have limited the development of effective chemotherapy administration protocols and combination therapies. Drug delivery devices that can properly target chemothe...

Up to date, the way in which metal nanoparticles are cleared in vivo has yet to be elucidated well. Herein, we report a novel intestinal goblet cell-mediated in vivo clearance pathway to remove metal nanoparticles. Typical metal nanoparticles such as triangular silver nanoplates, magnetic nanoparticles, gold nanorods, and gold nanoclusters were sel...

How to eradicate Helicobacter pylori (H. pylori) in vivo with antibiotic resistance owns tremendous clinical requirement. Herein, gold nanostars were conjugated with acid-sensitive cis-aconitic anhydride modified anti-H. pylori polyclonal antibodies, resultant pH sensitive gold nanostars@H. pylori-antibodies nanoprobes (GNS@Ab) were employed for th...

p>Creating ways to control drug activation at specific tissues while sparing healthy tissues remains a major challenge. The administration of exogenous triggers offers the possibility for precise and traceless drug activation. However, ensuring localization of the trigger as well as the prodrug at the diseased tissue is complex while essential for...

In spite of remarkable improvements in cancer treatments and survivorship, cancer still remains as one of the major causes of death worldwide. Although current standards of care provide encouraging results, they still cause severe systemic toxicity and also fail in preventing recurrence of the disease. In order to address these issues, biomaterial-...

Over the last decades, considerable efforts have been put into developing active nanocarrier systems that cross the blood brain barrier (BBB) to treat brain-related diseases such as glioma tumors. However, to date none have been approved for clinical usage. Here, we show that a human H-ferritin (HFn) nanocarrier both successfully crosses the BBB an...

Mesenchymal stem cells are multipotent adult stem cells capable of generating bone, cartilage and fat, and are thus currently being exploited for regenerative medicine. When considering osteogenesis, developments have been made with regards to chemical induction (e.g. differentiation media) and physical induction (e.g. material stiffness, nanotopog...

MTT analysis. (A) MG63 cells and (B) MSCs treated with each GNP (50nM oligo, 30% PEG) type for 48 hours (PEG, NS, 3A, 5A) (n = 3; error bars indicate SD). (TIF)

List of fluidigm primers used in this study. Primer list used for fluidigm analysis, detailing the gene function and the forward and reverse sequences used. Those with * indicate housekeeping genes. (PDF)

ICP-MS analysis. (A) MG63s and (B) MSCs treated with GNPs (50nM, 30%) for 48 hours. All GNP species were found within both cell types. Each lysate has an n = 3, error bars denote SD. (TIF)

AntagomiR sequences. S1 Table showing the oligomer sequences used for GNP-antagomiR functionalization. GC % relates to the melting temperature; the greater the GC content the higher the melting temperature. AntagomiR-31 5’, is designed to bind with the corresponding miR-31 5’ sequence. The same principle relates to antagomiR-31 3’, which binds with...

GNP saturation with thiolated PEG. (A) Absorbance spectra of DTNB after reaction with the thiolated PEG. (B) Standard calibration curve for PEG chains, whose concentration can be calculated via the following equation Abs412 = 26.229× [HS-PEG, mg/mL] + 0.0671. (C) Variation of the excess of PEG thiolated chains as a function of the initial concentra...

Cell-penetrating peptides (CPPs) have been widely explored as an effective tool to deliver a variety of molecules and nanoparticles into cells due to their intrinsic property to translocate across cell membranes. CPPs are easier to synthesize and functionalize, and their incorporation into delivery vehicles could be achieved by both non-covalent an...

Fungi, which are common in the environment, can cause a multitude of diseases. Warm, humid conditions allow fungi to grow and infect humans via the respiratory, digestive and reproductive tracts, genital area and other bodily interfaces. Fungi can be detected directly by microscopy, using the potassium hydroxide test, which is the gold standard and...

In 1985, the serendipitous discovery of fullerene triggered the research of carbon structures into the world of symmetric nanomaterials. Consequently, Robert F. Curl, Harold W. Kroto and Richard E. Smalley were awarded the Noble prize in chemistry for their discovery of the buckminsterfullerene (C60 with a cage-like fused-ring structure). Fullerene...

Systemic administration of therapeutic agents has been the preferred approach to treat most pathological conditions, in particular for cancer therapy. This treatment modality is associated with side effects, off-target accumulation, toxicity, and rapid renal and hepatic clearance. Multiple efforts have focused on incorporating targeting moieties in...

Light-based diagnostics and therapy have become indispensable tools in the field of cancer nanomedicine. Various optical imaging modalities with tomographic capability have been developed to visualize cellular and organismic distributions of molecules. Microscopic pharmacokinetics and the tumor-targeting efficacy of nanoscale effectors can now be p...

Nanomaterials can be used to probe, sense and treat metastasis while facilitating in depth understanding of disease associated mechanisms. Leveraging the potential of nanomedicine to combat cancer spread at each stage of the metastatic process while exploiting different administration routes may facilitate the development of new cancer therapeutic...

Metastasis is the primary cause for mortality in breast cancer. MicroRNAs, gene expression master regulators, constitute an attractive candidate to control metastasis. Here we show that breast cancer metastasis can be prevented by miR-96 or miR-182 treatment, and decipher the mechanism of action. We found that miR-96/miR-182 downregulate Palladin p...

Epigenetic modifications sit 'on top of' the genome and influence DNA transcription, which can force a significant impact on cellular behavior and phenotype and, consequently human development and disease. Conventional methods for evaluating epigenetic modifications have inherent limitations and, hence, new methods based on nanoscale devices are ne...