Advanced Nanomaterials for Cancer Therapy: Gold, Silver, and Iron Oxide Nanoparticles in Oncological Applications

Abstract

Cancer remains one of the most challenging health issues globally, demanding innovative therapeutic approaches for effective treatment. Nanoparticles, particularly those composed of gold, silver, and iron oxide, have emerged as promising candidates for changing cancer therapy. This comprehensive review demonstrates the landscape of nanoparticle-based oncological interventions, focusing on the remarkable advancements and therapeutic potentials of gold, silver, and iron oxide nanoparticles. Gold nanoparticles have garnered significant attention for their exceptional biocompatibility, tunable surface chemistry, and distinctive optical properties, rendering them ideal candidates for various cancer diagnostic and therapeutic strategies. Silver nanoparticles, renowned for their antimicrobial properties, exhibit remarkable potential in cancer therapy through multiple mechanisms, including apoptosis induction, angiogenesis inhibition, and drug delivery enhancement. With their magnetic properties and biocompatibility, iron oxide nanoparticles offer unique cancer diagnosis and targeted therapy opportunities. This review critically examines the recent advancements in the synthesis, functionalization, and biomedical applications of these nanoparticles in cancer therapy. Moreover, the challenges are discussed, including toxicity concerns, immunogenicity, and translational barriers, and ongoing efforts to overcome these hurdles are highlighted. Finally, insights into the future directions of nanoparticle-based cancer therapy and regulatory considerations, are provided aiming to accelerate the translation of these promising technologies from bench to bedside.

Keywords: cancer therapy; combination therapy; diagnostic; drug delivery; gold nanoparticles; imaging, iron oxide nanoparticles; metallic nanoparticles; personalized medicine; silver nanoparticles.

Figure 1

Interaction of drugs and tumor microenviroment (TME). The tumor extracellular matrix (ECM) creates barriers that reduce therapeutic efficiency in solid tumors. Dense ECM hinders drug diffusion, and induces hypoxia and metabolic stress, leading to drug resistance and reduced radiotherapy efficacy. Immune cells, such as CAR T cells, are either trapped by tumor signals or obstructed by the ECM, preventing effective tumor targeting. http://biorender.com.

Figure 2

Overview of the biological barriers that nanoparticles can overcome (inner ring) and precision medicine applications that may benefit from nanoparticles (outer ring). Intelligent nanoparticle designs can navigate cellular uptake challenges, immune system evasion, and targeted tissue delivery, thus enhancing drug delivery mechanisms. Applications include chimeric antigen receptor (CAR) therapies, epidermal growth factor receptor (EGFR)‐targeted treatments, EPR effect, and delivery of guide RNA (gRNA) and ribonucleoprotein (RNP) complexes. These advancements have the potential to accelerate the clinical translation of precision medicines. Reproduced Copyright Nature Reviews Drug Discovery 2021.^{[ 2 ]}

Figure 3

In the interendothelial cell extravasation mechanism, nanoparticles are transported through gaps of 100–500 nm in diameter. d _C, the intercellular gap distance in capillaries; d _MV, the intercellular gap distance in mother vessels; t _C, the thickness of endothelial cells lining the capillaries; t _MV, the thickness of endothelial cells lining the mother vessels. Copyright Nature Reviews 2016.^{[ 1 ]}

Figure 4

Application of AuNPs in cancer diagnosis, imaging, and therapy.

Figure 5

AuNPs‐based stimuli‐responsive drug delivery system for the co‐delivery of siRNA and chemotherapeutic drugs against pancreatic tumour cells. Copyright Environmental Research 2023.^{[ 4 ]}

Figure 6

Ausome consists of a gold nanoparticle core surrounded by a bacterial component shell. Upon intravenous injection, it triggers a systemic immune response through microorganism‐derived danger signals, activating immune cells and releasing pro‐inflammatory cytokines. After tumor accumulation, laser irradiation induces mild hyperthermia, enhancing blood flow and vascular permeability, which promotes the infiltration of immune cells into the tumor. This targeted immune modulation amplifies immune responses within the tumor microenvironment while avoiding the side effects associated with high systemic doses of immunomodulators.^{[ 3 ]} Copyright Nature Communications 2023. We are adapting under CC BY license by Springer Nature.

Figure 7

Overview of various strategies for synthesizing AgNPs with anticancer properties. These methods include plant‐based synthesis, biopolymer‐based synthesis, microwave‐assisted synthesis, microbial synthesis, and chemical/photochemical reduction. Functionalization of AgNPs with biomolecules such as DNA, aptamers, and antibodies tailors their properties for enhanced anticancer activity.AgNPs with anticancer properties.

Figure 8

Cancer cell targeting strategies using AgNPs. This diagram illustrates the various approaches for targeting cancer cells with AgNPs, including passive targeting via the EPR effect, increased circulation, and active targeting through receptor‐mediated endocytosis. AgNPs can also be functionalized with ligands for specific binding to cancer cell surface receptors, improving bioavailability and therapeutic efficacy.

Figure 9

Schematic diagram illustrating hyperthermia and its role in neutralizing tumor cells. When IONPs are injected into the tumor and an external magnetic field is applied, the localized temperature increases, leading to the destruction of tumor cells.

Figure 10

Diagram demonstrating the use of IONPs for targeted drug release to tumor cells. When drug‐loaded IONPs are injected, the drug is released either in response to the acidic pH at the tumor site or through the application of an external magnetic field, enabling controlled and targeted drug delivery.

Figure 11

Maximizing therapeutic benefits of cancer nanomedicine through the stimuli‐triggered dynamic integration of multistage tumor targeting was adapted from ref. [358] with permission. Copyright 2023, The authors, Nature, Creative Commons license.

Figure 12

Photothermal and photodynamic effects of Au₂₅(Capt)₁₈ was adapted from ref. [377] with permission. Copyright 2019, Royal Society of Chemistry.

Figure 13

Combined RT and PTT in vivo studies were adapted from ref. [377] with permission.

Figure 14

The synergistic effect and immune response elicited by IONP−C/O@LPs. IONPs co−delivered CpG DNA to active immature DCs, synergistically enhancing immune response and antitumor effect. This figure was adapted from ref. [396] with permission. Copyright 2022, Wiley‐VCH GmbH.

Figure 15

Schematic representation of the advantages of utilizing hybrid metal nanoparticles (Au@AgNPs, IO@AuNPs, IO@AgNPs) in cancer therapy. These nanoparticles enhance therapeutic outcomes through passive targeting via the enhanced permeability and retention (EPR) effect, increased blood circulation, and active targeting via endocytosis. The use of ligands on nanoparticles facilitates specific targeting to cancer cell surface receptors, while the nanoparticles also improve bioavailability of therapeutic agents, providing greater efficacy compared to conventional drug delivery methods. Image created using BioRender (http://biorender.com).

Figure 16

Schematic illustrations of a) the synthesis of DOX/Au@Pt‐cRGD, and b) ROS scavenging by catalyzing the platinum shell while attenuating DOX‐induced organ oxidative injury were adapted from ref. [418] with permission.

Figure 17

Engineered nanomedicines to trigger immunogenic cell death (ICD) of cancer cells using various approaches were adapted from ref. [434] with permission. Copyright 2024, The authors, Elsevier B.V., on behalf of the Chinese Pharmaceutical Association and Institute of Materia, Chinese Academy of Medical Sciences.

Figure 18

Illustration of the Gd‐MOF‐5 nanoparticles to modulate immunosuppressive PS and immunostimulatory ICD signals was adapted from ref. [443] with permission. Copyright 2021, Elsevier Ltd.