Gold nanoparticles as antiangiogenic and antimetastatic agents (2023)


Cancer is a group of diseases characterized by fast replicating and genetically unstable cells able to escape growth suppression and apoptosis.1 These behaviors may result in migration, invasion, and metastasis, resulting in cancer spread to distant sites. Cancer cells (CCs) can also evade the immune system and reprogram their metabolism to sustain proliferation. These features were recognized as the six hallmarks of cancer by Hanahan and Weinberg in 2000.2 Since then, the hallmarks of cancer have been further extended and connected among each other due to advancements in oncological research.1, 2 These hallmarks are gained over a multistep process called tumorigenesis, in which the interactions among CCs and the surrounding area are crucial.3 Once mutated, several protooncogenes and gene suppressors can promote cancer development.4 From epidemiology studies, tumorigenesis normally spans over decades and the tumors require the accumulation of up to eight rate-limiting events to be clinically detectable.5 Occasionally, the process may be faster, and this may be due to the differentiation status of the progenitor cells and the involvement of mutated oncogenes.5 Despite the progress in cancer prevention and treatment, cancer is still the second leading cause of death worldwide, accounting for 21% of all deaths, with metastasis being the main cause of death for oncological patients.6, 7 Indeed, the spread of tumor cells to distal tissues and organs reduces the effectiveness of the actual treatments.

Promising approaches for cancer treatment rely on nanomedicine, which may improve the therapeutic outcome of anticancer drugs by balancing drug efficacy and toxicity.8 Because nanomedicine effects in preclinical trials are usually more significant than those in clinical trials, only a few nanoproducts have been approved for clinical practice to date.9 In this context, noble metal nanomaterials may serve as the final advancement for the specific treatment of metastases and angiogenesis due to the peculiar features of their intrinsic chemistry. Among several metals (silver, copper, and platinum), GNPs have been the most extensively investigated as antiangiogenic and antimetastatic therapeutics due to their versatility and particularly effective action, even without active molecules on their surfaces.10 However, the synthetic procedure can itself modulate the antiangiogenic or proangiogenic outcome of GNP treatment.11 While several reviews have focused on GNPs as antiangiogenetic agents, a critical review regarding their exploitation as antimetastatic agents is still lacking despite the interdependence between these phenomena.12, 13

In this review, we focused on the potential application of GNPs to two cancer hallmarks: angiogenesis and metastasis. Besides the systematic review of the actual literature together with a critical analysis of the investigations, the challenges and perspectives on the potential contribution of GNPs to cancer management are provided to stimulate a further discussion on this topic of growing interest.

Section snippets


GNPs are materials ranging between 1 and 100nm in size. The procedures for GNP synthesis have been extensively described elsewhere.14, 15 In the bottom-up approach, tetrachloroauric acid is reduced to metal gold, which can grow in nanoparticles (NPs) of different geometry and size depending on the reduction conditions. The protocols can be modified to obtain gold clusters (<2 nm), nanospheres (5–150nm), nanorods (20nm to several µm), nanoplates, nanostars, and nanocages.15 Nanosized gold


Fast replicating CCs require the sustained intake of nutrients and oxygen, and need to be at most 100–200µm distant from the vessel to be nourished.2, 32 Once the neoplasia is not efficiently provided by nutrients, it starts stimulating blood vessel development from the existing vasculature. This process is called angiogenesis, and in physiological conditions, is strictly regulated by proangiogenic and antiangiogenic factors. In cancer, the equilibrium between the two counterpart factors is

GNPs as carriers

GNPs have been extensively conjugated with antiangiogenic agents, and frequently with other anticancer drugs to support (supra)additive effects. Mukherjee et al.58 prepared a ‘2 in 1’ system comprising gemcitabine as the anticancer drug and an anti-VEGF antibody (AbVF) on 5-nm GNPs. The investigations have been performed in the 786-O renal adenocarcinoma cell line and in human umbilical vein endothelial cells (HUVECs), where gemcitabine maintained its efficacy independently on AbVF, whereas

GNPs as antiangiogenic agents

Bhattacharya et al.72 evaluated the antiangiogenic effects of 5-nm borohydride-stabilized GNPs on HUVECs. GNPs were not cytotoxic in HUVECs, whereas they limited VEGF165-induced proliferation. Interestingly, this effect was not observed for VEGF121-induced proliferation. VEGF165 and VEGF121 are diffusible VEGF isoforms that bind VEGFR1/2, whereas only VEGF165 also binds neuropilin1 (NRP1) on ECs.73, 74, 75 NRP1 is a co-receptor of VEGFR; thus VEGF165 intensifies its signaling in ECs.76 The


Metastasis is a process in which CCs escape the primary site, disseminating in the body and colonizing distant organs, eventually originating secondary tumors.97 Metastasis is considered the final stage of cancer progression and is responsible for the majority of cancer-related relapses and deaths.7

The invasion of the ECM can commence from single, clusters, or sheets of CCs, but less than 0.02% of circulating CCs effectively originate metastases.98, 99 The collective migration demands

Targeting metastatic pathways

Antimetastatic drugs may interact with key elements of cancer migration and invasion, such as the EMT, ROS equilibrium, and chronic inflammation.109 Even though each step of the metastatic development can be a target, metastasis development mechanisms strongly depend on both the primary tumor and new metastatic niche features. Therefore, targeting metastatic pathways requires a deep understanding of the tumor-specific mechanisms involved.107 Traditionally, antimetastatic drugs are supposed to

GNPs as therapeutic tools

The interdependence between angiogenesis and metastasis has suggested the potential antimetastatic application of antiangiogenic agents. Due to the ability of GNPs to repress EC proliferation and normalize tumor vessels, the antimetastatic effects of GNPs have been investigated (Table 1). Arvizo et al.140 compared different sizes of GNPs to evaluate their effects on the proliferation and migration of ovarian CCs. The 20-nm GNPs were selected because of their effect on cell proliferation and

Concluding remarks

Invasion and metastases are central features of cancer malignancy and constitute the primary cause of death for >90% of oncological patients.104 Metastasis is the final frontier in cancer research for which more efficacious therapies are needed. In this context, findings on tumor dynamics are vital to identify and conceptualize novel strategies for improved cancer management and treatment. Interestingly, antiangiogenic agents may themselves act on metastasis, as these two cancer hallmarks are

Declaration of interests

The authors have no conflicts of interest to declare.


Figures have been created with This work was supported by the MFAG 2017 - ID 19852 from Associazione Italiana per la Ricerca sul Cancro (AIRC) granted to V. Voliani (P.I.).

Agata Zamborlin graduated in Pharmaceutical Chemistry and Technology at the University of Padua (Italy) with a Master’s thesis on targeted gold nanoparticles for the delivery and controlled release of anticancer drugs. She is a PhD student in Nanoscience at Scuola Normale Superiore and Istituto Italiano di Tecnologia under the supervision of Professor Valerio Voliani. Her research interest is the development of biodegradable inorganic nanotherapeutics for the establishment of novel treatment

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Gold nanoparticles as antiangiogenic and antimetastatic agents (1)

Agata Zamborlin graduated in Pharmaceutical Chemistry and Technology at the University of Padua (Italy) with a Master’s thesis on targeted gold nanoparticles for the delivery and controlled release of anticancer drugs. She is a PhD student in Nanoscience at Scuola Normale Superiore and Istituto Italiano di Tecnologia under the supervision of Professor Valerio Voliani. Her research interest is the development of biodegradable inorganic nanotherapeutics for the establishment of novel treatment approaches for the management of oral and pancreatic carcinoma with a special focus on antimetastatic agents.

Gold nanoparticles as antiangiogenic and antimetastatic agents (2)

Valerio Voliani received his MSc in Chemistry and PhD in Molecular Biophysics from Scuola Normale Superiore (Pisa, Italy). He is Professor of Inorganic and General Chemistry at the Department of Pharmacy (University of Genoa), and group leader researcher at Istituto Italiano di Tecnologia. His efforts are devoted to the translation of hybrid nanotechnologies to clinical practice by promoting noninvasive treatments for neoplasms and communicable diseases. His main interests are related to photothermal conversion, drug delivery, photoacoustic/ultrasound imaging, combined therapies, and alternative in vivo cancer models. He is actively engaged in scientific dissemination.

© 2022 Elsevier Ltd. All rights reserved.


Are gold nanoparticles an anticancer agent? ›

Atable gold nanoparticles show more significant anticancer activity against HepG2 and A549 cells at 100 μg concentration of nanoparticles.

Can gold nanoparticles deliver drugs to cancer patients? ›

Gold nanoparticles (GNPs), a type of nanocarrier with unique optical properties and remarkable biocompatibility, have the potential to influence the fate of cancer by delivering drugs, nucleic acids to cancer cells and tissues.

Are gold nanoparticles FDA approved? ›

Gold nanoparticles (AuNPs) are among the FDA-approved metallic nanoparticles and have shown great promise in a variety of roles in medicine. They were used as drug delivery, photothermal (PT), contrast, therapeutic, radiosensitizing, and gene transfection agents.

How are gold nanoparticles used in breast cancer? ›

Through plasmon resonance, gold nanoparticles can induce hyperthermia with NIR laser. Gold's high atomic number enables it to enhance the effect of radiotherapy, which can be amplified by mild, laser-induced hyperthermia.

Are gold nanoparticles antimicrobial? ›

The antimicrobial action of gold NPs for Gram-positive and Gram-negative bacteria is different. The main difference is the structure of the membrane i.e., the peptidoglycan layer's thickness, which is an important part of pathogenic bacteria.

What are the disadvantages of gold nanoparticles? ›

The main limitation of the magnetic nanoparticle approach is the fact that it is difficult to generate fine-tuned and precise treatment of tumors due to the fact that AMF fields are generally targeted toward the whole body in contrast to the tumor specifically as seen with photothermal approaches (Dennis et al., 2008).

How do gold nanoparticles destroy cancer cells? ›

Gold nanoparticles absorb incident photons and convert them to heat to destroy cancer cells. Due to their unique optical properties as a result of LSPR, gold nanoparticles absorb light with extremely high efficiency (cross section at ~10 9 M1 cm1), which ensures effective PTT at relatively low radiation energy.

How do gold nanoparticles fight cancer? ›

As a result, you can apply less radiation to the tissue, but the nanoparticles will amplify the effects of the radiation to kill the cancer cells and to spare the surrounding normal tissues. The effect of the local radiation dose enhancement by gold nanoparticles is called radiosensitization.

What are the disadvantages of nanoparticles in cancer treatment? ›

However, this technique has disadvantages, such as its lethal effect on normal cells within the body. Accordingly, therapy provided for the tumor cells is lethal for the normal cells, leading to neural toxicity, suppression of bone marrow and cardiomyopathy, etc.

Are gold nanoparticles toxic to humans? ›

Some studies have shown that AuNPs are not toxic, though many other studies contradict this statement. In order to have a holistic inference, more studies are required that will focus on characterization of NPs and changes of physical properties before and after treatment with biological media.

Are gold nanoparticles inflammatory? ›

Gold nanoparticles have proven to have anti-angiogenesis and anti-inflammatory properties and can be used to treat retinal diseases [8]. In the previous laser-induced choroidal neovascularization (CNV) animal model, intravenous injection of gold nanoparticles showed significant anti-angiogenic properties [11].

What countries banned nanoparticles? ›

Canada, Australia and Austria have prohibited nanoparticles smaller than 100 nanometers(nm) from organic foods.

What is the conclusion of gold nanoparticles in cancer treatment? ›

Gold nanoparticle thermal therapy

Hyperthermia is known to induce apoptotic cell death in many tissues and has been shown to increase local control and overall survival in combination with radiotherapy and chemotherapy in randomised clinical trials [32-34].

What happens to gold nanoparticles in cells? ›

Summary: Gold nanoparticles, which are supposed to be stable in biological environments, can be degraded inside cells. Gold nanoparticles, which are supposed to be stable in biological environments, can be degraded inside cells.

Which nanoparticles for anticancer? ›

Silica Nanoparticles

Mesoporous silica NPs are considered one of the best drug carriers due to their better pharmacokinetic properties. They have been extensively used in immunotherapy. According to a study, colorectal cancer cells have shown successful uptake of camptothecin-loaded mesoporous silica NPs.

Are gold nanoparticles in Covid 19 treatment? ›

Our reported data show that antibody attached gold nanoparticles bind to SARS-CoV-2 spike protein, thereby inhibiting the virus from binding to cell receptors, which stops virus infection and spread. It also has the capability to destroy the lipid membrane of the virus.

What are gold nanoparticles highly effective as? ›

Gold nanoparticles, having a strong photoelectric absorption coefficient in the kilovoltage photon energy range, is recognized as an effective radiosensitizing agent with a wide range of radiobiological applications.

What is unusual about gold nanoparticles? ›

Gold nanoparticles can be coated with different materials such as small molecules, biomolecules, and polymers because of these nanoparticles' versatile surface chemistry. Therefore, they have a wide range of applications in different fields, such as catalysis, sensory probes, drug delivery, and therapeutic agents.

Are gold nanoparticles drug carriers? ›

Colloidal gold nanoparticles (AuNPs) are of interest as non-toxic carriers for drug delivery owing to their advanced properties, such as extensive surface-to-volume ratio and possibilities for tailoring their charge, hydrophilicity and functionality through surface chemistries.

What are bad things about nanoparticles? ›

Materials which by themselves are not very harmful could be toxic if they are inhaled in the form of nanoparticles. The effects of inhaled nanoparticles in the body may include lung inflammation and heart problems.

What is the shelf life of gold nanoparticles? ›

These expiration dates can range from 30 days to 1 year depending on the type of product. The specifications shown in the typical Certificate of Analysis detail physical properties as size, charge, absorbance, and more depending on the product.

How does the body get rid of nanoparticles? ›

Even insoluble nanoparticles which reach the finely branched alveoli in the lungs can be removed by macrophage cells engulfing them and carrying them out to the mucus, but only 20 to 30 per cent of them are cleared in this way. Nanoparticles in the blood can also be filtered out by the kidneys and excreted in urine.

Can nanoparticles cause cell death? ›

Nanoparticles can disrupt normal cellular function via cytotoxic stress, and are responsible for membrane damage (22). There are several genes and proteins reported to be involved in apoptotic pathways.

What cells can nanoparticles cause damage to? ›

Here, we show that cobalt-chromium nanoparticles (29.5 +/- 6.3 nm in diameter) can damage human fibroblast cells across an intact cellular barrier without having to cross the barrier.

How do nanoparticles cause cancer? ›

Peng and team found that NanoEL speeds up the movement of cancer cells from the original tumor site to new sites and helps the cancer cells that are already in motion evade blood circulation.

How can nanotechnology cure cancer? ›

Nanotechnology can help to make cancer treatments safer and more precise. Specially designed nanoparticles deliver medicines like chemotherapy straight to the tumor. They don't release the medicine until they reach it. This stops the drugs from damaging healthy tissues around the tumor.

Are nanoparticles carcinogenic? ›

Copper-oxide nanoparticles

Elevated oxidative stress may lead to DNA damage, which in turn has the potential for carcinogenesis.

What are nanoparticles pros and cons? ›

Nanotechnology offers the potential for new and faster kinds of computers, more efficient power sources and life-saving medical treatments. Potential disadvantages include economic disruption and possible threats to security, privacy, health and the environment.

Does chemotherapy use nanoparticles? ›

Nanoparticles are used as a drug delivery carrier. Once taken up by cells, the drug is released.

How long do nanoparticles stay in the body? ›

The blood half-lives of the various iron oxide nanoparticles currently in clinical use vary from 1 h to 24-36 h [69]. However, specific biodistribution and clearance parameters depend on particle properties such as surface characteristics, shape, and size [71].

Do gold nanoparticles dissolve? ›

Gold Nanoparticles Dissolve Extracellularly in the Presence of Human Macrophages.

Are gold nanoparticles cytotoxic? ›

Gold nanoparticles (AuNPs) exert cytotoxic effects in MDA-MB-231 cells through the induction of oxidative stress.

What is the antiviral activity of gold nanoparticles? ›

The antiviral activity of the AuNPs-As showed a reduction of PFU of 57.07% at 10 μg/mL (Figure 3) obtaining an EC50 of 8.829 μg/mL (Table 1).

Why are scientists worried about nanoparticles? ›

Because elements at the nanoscale behave differently than they do in their bulk form, there's a concern that some nanoparticles could be toxic.

What is the top 1 country that uses nanotechnology? ›

Overall, Switzerland plays a significant role in the global nanotechnology community and is known for its high-quality research and innovation in this field.

What food has nanoparticles? ›

Common food-related products that contain nanotechnology include candies (M&M's, Skittles), baby bottles, and plastic storage containers.

What are the recent biomedical applications of gold nanoparticles? ›

They have suitable properties for controlled drug delivery, cancer treatment, biomedical imaging, diagnosis and many others, due to their excellent compatibility with the human organism, low toxicity and tunable stability, small dimensions, and possibility to interact with a variety of substances.

In which treatment gold nanoparticle are used? ›

Due to their unique properties, such as absorption and scattering of electromagnetic radiation, gold nanoparticles are of particular interest for the application in photothermal therapy (PTT). This treatment strategy involves the use of electromagnetic radiation to generate heat for thermal destruction of cancer cells.

What are the antioxidant effects of gold nanoparticles? ›

observed the effective role of gold nanoparticle (AuNP) as an antioxidant agent by inhibiting the formation of reaction oxygen species (ROS) and scavenging the free radicals.

What effect do nanoparticles have on DNA? ›

This cellular uptake of nanoparticles enhances its interaction with DNA, leading to structural and functional modification (DNA damage/repair, DNA methylation) into the DNA.

Can nanoparticles damage DNA? ›

Some nanoparticles, if they're based on certain metals, can interact with the hydrogen peroxide that is present in every cell, and convert it to a hydroxyl radical, which can enter the nucleus and then you potentially have DNA damage.

How do gold nanoparticles interact with DNA? ›

Single-stranded DNA can be adsorbed by citrate-capped Au nanoparticles (AuNPs), resulting in increased AuNP stability, which forms the basis of a no. of biochem. and anal. applications, but the fundamental interaction of this adsorption reaction remains unclear.

Are gold nanoparticles anticancer agents? ›

Atable gold nanoparticles show more significant anticancer activity against HepG2 and A549 cells at 100 μg concentration of nanoparticles.

What nanoparticles for brain tumor imaging? ›

Magnetic nanoparticles (MNPs) represent a promising nanomaterial for the targeted therapy and imaging of malignant brain tumors. Conjugation of peptides or antibodies to the surface of MNPs allows direct targeting of the tumor cell surface and potential disruption of active signaling pathways present in tumor cells.

What nanomaterials are used for angiogenesis? ›

Nanomaterials not only serve as carriers that effectively deliver factors such as angiogenesis-related proteins and mRNA but also simulate the nano-topological structure of the primary ECM of blood vessels and stimulate the gene expression of angiogenic effects facilitating angiogenesis.

What can gold nanoparticles be used for? ›

Catalysis - Gold nanoparticles are used as catalysts in a number of chemical reactions. The surface of a gold nanoparticle can be used for selective oxidation or in certain cases the surface can reduce a reaction (nitrogen oxides). Gold nanoparticles are being developed for fuel cell applications.

What is the role of gold in anticancer activity? ›

Gold complexes have attracted significant attention as potential anticancer compounds, due to the fact that many gold(I) and gold(III) compounds inhibit the growth of cancer cells, including those in cisplatin-resistant tumors [1-5].

Why are gold nanoparticles used in medicine? ›

Au NPs have been used to target delivery of chemotherapeutic agents, complement radiation and thermal therapy, and enhance contrast for in vivo imaging of the tumor in a variety of cancer types and diseased organs.

How can nanoparticles possibly help to fight cancers? ›

Phototherapy is used to induce apoptosis in cancer cells by employing light, heat, and radiation. Photosensitizers like nanoparticles enhance the killing effect by targeting signaling pathways and the immune system.

What nanoparticles are used in chemotherapy? ›

The technique involves storing a cancer drug inside tiny objects called nanoparticles. Using this method, researchers were able to shrink tumors in mice while using smaller doses of the drug to reduce harmful side effects. The chemotherapy drug cisplatin is an effective cell killer.

Why is gold anti inflammatory? ›

Uses. While the exact mechanism of gold's anti-inflammatory effect is not fully understood, gold salts appear to stop cells from releasing chemicals that can harm tissues. In the mid-20th century, researchers found injectable gold has clinically significant benefits in the short-term treatment of RA.

Does gold reduce radiation? ›

Gold, a high Z material, is capable of absorbing radiation at significantly higher rates than tissue.

Why is gold used in drug therapy? ›

A procedure that uses gold salts (a salt form of the metal element gold) to treat diseases, such as rheumatoid arthritis. The gold salts stop cells from releasing chemicals that can harm tissues.

Should nanoparticles be used in medicine? ›

Nanotechnology in medicine is very important from a therapeutic standpoint, and it can also be vital from a diagnostic perspective. By using nanoparticles, a drug can be accurately delivered to the targeted region in the body.


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