Emerging Trends in Silver Nanoparticle Therapies for Breast Cancer: A Comprehensive Review

INTRODUCTION

Breast cancer is the most frequently diagnosed cancer among women and a dominant cause of mortality, with an estimated 310,720 new cases and 42,250 deaths anticipated in 2024 alone. The disease is classified into molecular subtypes, including Luminal A, Luminal B, HER2-enriched, and Triple-Negative Breast Cancer (TNBC) Nanotechnology offers advanced delivery systems that provide better stability, targeted delivery, and extended blood circulation compared to traditional methods. While few nanoscale systems like paclitaxel-albumin complexes are FDA-approved, research into metal nanoparticles like AgNPs continues to expand (Figure 1).

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Numerous delivery systems are available, one of them is nanomedicine that have been used for drug delivery. It is more advantageous than traditional methods due to its targeted drug delivery system, stability and extended blood circulation (Fraguas-Sánchez et al., 2025 and Fu et al., 2025). Nanotechnology provides different systems or carriers that can deliver the drug at targeted site. Despite extensive research in Pharmaceutical nanotechnology, the FDAs complete approval process has been successfully completed by just a handful of nanoscale drug delivery systems, including the landmark paclitaxel-albumin complex and sterically stabilized liposomal doxorubicin (Mugundhan et al., 2024). The results of various studies are integrated into the thematic sections below: Types of Nanoparticles: NPs are classified into carbon, metal, ceramic, semiconductor, and polymeric types. Biological Activity: Plant-derived AgNPs (from leaves, seeds, or roots) show diverse activities, including antibacterial, anticancer, and antiviral properties.

Breast Cancer

Breast cancer is a worldwide risk with high death rates (Martínez-Sanmiguel et al., 2024). Breast cancer exhibit significant molecular heterogeneity, with distinct classifications emerging from differential expression patterns of Harmone receptors and growth factor proteins. One subtype is Triple Negative Breast Cancer (TNBC), named due to lack of progesterone receptors, estrogen receptors and Human Epidermal Growth Factor Receptor-2(HER-2) which are commonly present in other breast cancers (Lehmann et al., 2011). Most of the breast cancers are due to overexpression of the Human Epidermal Growth Factor Receptor 2(HER2) (Choong et al., 2022). Monoclonal antibodies like trastuzumab had significantly raised the prognosis of patients for the patients with overexpression of HER2 (Chen et al., 2023; Vega-Rubín-De-Celis et al., 2023). PYROTINIB, a small molecule has shown significant enhancement in both disease free and overall survival rates among the patients diagnosed with HER2 positive breast cancer¹². There are many adverse effects with the existing therapy and development of resistance due to genetic mutations. Therefore there are recent advances in cancer therapy with nanostructures like metal nanoparticles and these are available and can be formulated through a Eco-friendly environment to minimise the adverse effects with hazardous chemicals. Nanomaterials are approved as anticancer agents by the FDA. Nanoparticles are less toxic and can be used as Biomedicine (Liu et al., 2023; Yazdi et al., 2016).

Nanoparticles As Anticancer Agents

Nanotechnology has been a prominent field of research since late 20^th century. Nanotechnology has enabled the creation of a wide variety of materials at nanoscale nanoparticles are one of those wide variety of materials (Khan et al., 2019). Nanoparticle is defined as a particle with size lessthan 100 nm or ultrafine particle nanoparticles have different applications in various sectors ranging from carrier for drug to the target site and gene delivery into tumors. Nanomaterials differ from other bulk substances based on the size of the particle (Zahra et al., 2020).

Types of Nanoparticles

Depending on physical and chemical properties nanoparticles have been classified as carbon NPs, metal NPs, Ceramics NPs, Semiconductor NPs, Polymeric NPs (Khan et al., 2019).

Carbon Nanoparticles

Nanotubes and Fullerences are the two major types of carbon based NPs. These Nanoparticles feature various attachment sites on their surface, which can be modifies to connect with tissues, increasing their usage in targeted applications. Carbon nanotubes are essentially hollow, tube like structures formed by rolling a flat, single atom-thick layer of carbon atoms (Graphene) into a smooth, unbroken cylinder. These rolled sheets can be single sheet or double or multiple. If the sheets are single rolled, they can be called as Single Walled Nanotubes (SWNTs) and if they are multiple, they can be called as Multiple Walled carbon Nanotubes (MWNTs) (Bosi et al., 2003; Pagona et al., 2006).

Metal nanoparticles

Metal nanoparticles are prepared from the precursors of metals. Nanoparticles of metals such as copper, Silver, Gold have a broad range of absorption spectra. Metal nanoparticles have wide applications in research area (Khan et al., 2019). These nanoparticles consist of a dielectric center coted with a nanoscale gold layer, forming a core shell spherical geometry. These nanoparticles possess unique optical and chemical features that enhance their performance in imaging and therapeutic biomedical applications (Hirsch et al., 2006). Recently silver nanoparticles have made to explore their properties and potential uses such as antibacterial and anticancer treatments (Chen et al., 2009; Sun et al., 2003). Silver Nanoparticle (AgNPs) possesunstapped potential when compared to the relatively stable Gold Nanoparticles (AuNPs) (Desireddy et al., 2013).

Ceramics Nanoparticles

Ceramic Nanoparticle is inorganic materials that have characterized porous nature and recently gained prominence as carriers for drug delivery (Cherian et al., 2000). They have wide applications in catalysis, photodegradation of dyes etc. (Zahra et al., 2020).

Semiconductor Nanoaparticles

Semiconductor material contains both conductor and semiconductor properties and exhibit various applications. They play an important role in Photocatalysis, electronic devices (Khan et al., 2019).

Polymeric Nanoparticles

These nanoparticles are derived from organic compounds and a distinct term called Polymer Nanoparticle (PNP) is used for it. Attaching polymers to proteins decreases immunogenicity extends plasma half-life and improve protein stability. By utilizing the enhancing permeability and retention effect, polymer-drug conjugates specifically accumulate in tumors and enable cellular level drug delivery after being internalized (Lee et al., 2006). Importance of nanoparticles is because of their adaptable properties and their enhanced functioning or activity over their parent material. There are different methods of synthesizing the nanoparticles which may be hazardous and recent innovative using biological methods that are eco-friendly, safe and productive and this also called as green synthesis (Khan et al., 2019).

Synthesis of Nanoparticles

Nanoparticles can be prepared by the three methods such as physical method, Chemical method and green method (Divya et al., 2018; Hemmati et al., 2020). Chemical methods used for the synthesis of silver nanoparticles have a common strategy of reducing and stabilising agents to monitor different sizes and different shapes for the targeted delivery and the toxicity of this chemical method is due to reducing agents. Methods that produce nanoparticles with high energy input are with reduced stability, which results in unwanted chemical reactions and agglomeration, thus unsuitable for in vivo drug delivery. Therefore the usage of toxic organic solvents hinder their application in drug delivery for lung and breast cancer. Correspondingly methods like UV- initiated photoreduction, irradiation and electrochemical synthesis need a lot of energy to male nanoscale particles. Even Tollen’s method which uses carbohydrate still requires ammonia that results in toxic particles that makes them not entirely safe for drug delivery (Malik et al., 2018). Most of the studies are suggesting the use of green synthesis due to their use of nontoxic chemicals and low cost (Mescola et al., 2017; Peter et al., 2016; Castillo-Henríquez et al., 2020). Green synthesis means the use of plant and fruit extracts as reducing and stabilizing agents. For example eco-friendly preparation using orange peel extract which contains polyphenols and polysaccharides act as reducing agents, carboxylic, amino acid and citric acid that act as stabilising agents (Skiba et al., 2019). The most active constituent in orange is flavonoids that shows anticancer property (Tajaldini et al., 2020).

Preparation of AgNPs and Ag/RGONCs

Silver nitrate, Graphene Oxide and extract of orange peelare necessary for nanoparticle formulation. Silver nitrate was dissolved in deionized water to obtain a 1 nm aqueous solution. 50 mg of Graphene oxide was dissolved in 100 mL of deionised water. A mixture was prepared containing 160 mL of silver nitrate solution, 20 mL orange peel extract, and 20 mL graphene oxide suspension, with continuous mild agitation. The reaction mixture was kept at dark conditions at room temperature for 12 hr and finally the obtained powder was dried at 90ºC for at least 3 hr and ground into a fine powder for further characterization (Ahamed et al., 2025). Table 1 shows the source and the activity exhibited by the nanoparticle.

Drug delivery system

Nanoparticles ranging from 1 to 100 nm have emerged as pivotal agents in the realm of drug delivery owing to their unique physiochemically properties and versatile functionality. These nanoscale constructs can be engineered to transport therapeutic compounds with high specificity to designated biological targets. Their ability to markedly enhance pharmacological outcomes positions them as a cornerstone in the evolution of precision medicine. A fundamental challenge in the treatment of many pathological conditions lies in the targeted localisation of the therapeutic agents. Conventional formulations often suffer from suboptimal biodistribution, limited therapeutic index and poor selectivity, thereby compromising the clinical efficacy (Seleiman et al., 2017) (Figure 2).

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Advanced controlled release systems utilising nanoparticles enable site specific drug deposition, thereby maximising therapeutic impact on diseased tissue and minimising the systemic toxicity (KhademSadigh et al., 2025). Nanoparticle mediated delivery has been categorised into five functional modalities, they are Diagnostic imaging, oncologic therapeutics,photosensitizer transport, nucleic acid delivery and protein-based interventions. Each modality harnesses the precsion of nanotechnology to refine treatment accuracy, attenuate adverse effects and elevate clinical outcomes. Collectively these innovations are reshaping the landscape of contemporary medicine, particularly in the domains of molecular diagnostics and targeted therapeutics (Islam et al., 2025). Targeted drug delivery system has been considered as favorable compatibility within the human systems. These systems effectively reduced the survival rates of breast cancer lines 4T1 and MCF-7, while showing the minimal toxicity towards endothelial cells. Additionally they exhibited potent anti-tumor activity in live animal momodels. Various polymer- based delivery platforms have been thoroughly explored for treating initial and advanced stages of breast (Salari et al., 2022).

Applications

From the advanced drug administration methods Nanoparticle drug delivery had been adopted as the most advanced method (Kuddushi et al., 2025).The U.S Food and Drug administration has previously sanctioned multiple nanoparticle mediated chemotherapy platforms for breast cancer treatment, with numerous additional systems currently undergoing clinical evaluation. These drug delivery constructs based on polymeric nanocarriers, liposomal formulations, and paclitaxel loaded nanoparticles (Yang et al., 2022; Zhou et al., 2023). The Polymeric nanoparticles, in particular offer customizable surface architecture that can be engineered for permeability, biocompatibility and biodegradability. These carriers are synthesised using synthetic polymers or natural polymers. Their advantages include high drug encapsulation efficiency, scalable production and tunable release kinetics (Zhang et al., 2024) PLGA (Poly(Lactic-Co-Glycolic Acid)) is a synthetic polymer has the ability to inhibit p-glycoprotein activity, a mechanism that plays a critical role in overcoming multidrug resistance. Nanoparticles are also employed in combination therapy approaches for breast cancer, where multiple therapeutic agents are co-delivered to achieve synergistic effects. This strategy has been shown to enhance the treatment outcomes, mitigate the emergence of drug resistance and improve patient survival rates (Triantafyllakou et al., 2022). While siRNA loaded nanocarriers have demonstrated promising therapeutic potential, their efficacy is still subject to the complexities of in vivo interactions. To better evaluate novel treatment modalities, patient derived xenograft mouse models are considered superior to conventional human breast cancer cell lines. These models retain the molecular, cellular, genomic and epigenomic characteristics of actual tumours, offering a more accurate platform for translational research (Wang et al., 2024; Marinov et al., 2025). The prism analogy aptly represents the multifaceted nature of nanoparticles, high lightening their ability to adapt and optimise drug delivery systems for specific pathological conditions. These innovations not only enhance drug bioavailability but also minimise systemic toxicity and elevate therapeutic efficacy (Islam et al., 2025) (Figure 3).

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Nanoparticle-driven advances in precision drug delivery

Nanotechnology enabled therapeutic delivery systems are revolutionizing modern healthcare by facilitating precise and efficient transport of bioactive compounds. These platforms enhance drug solubility, molecular stability and site specific targeting by leveraging the distinct physiochemical traits of nanomaterials such as high surface to volume ration, turnable surface chemistry and ultra small dimensions. Recent advancements focuses on engineering ecofriendly and physiologically compatible nanovehicles, including lipid based vehicles, polymeric nanostructures and inorganic nanosysytems. Cutting edge surface engineering techniques and stimuli triggered release strategies are broadening their utility across diverse biomedical domains notably in immunomodulation, tissue regeneration and oncological therapies^60.The enhanced precision in targeting, regulating release profiles and improved dissolution and molecular stability provided by these nanocarrier systems significantly elevate the pharmacological availability of therapeutic agents. Moreover, their versatile drug - encapsulation potential enables the delivery of a broad spectrum of medicinal compounds while effectively navigating physiological barriers. These technological strides are paving the way for more refined and efficacious approaches to clinical drug administration (Tian et al., 2021; Guo et al., 2024).

1. Enhanced targeting efficiency,
2. Controlled drug release,
3. Improved drug solubility,
4. Versatility in drug loading,
5. Overcoming biological barriers.

Delivery of nanoparticles to cancerous cells

Nanoparticles are delivered to cancerous cells in two main ways i.e active and passive targeting. In active targeting (shown in Figure 4) nanoparticles are bind to specific receptors on cancer cells. These receptors are common on cancer cells than on normal cells. The receptors must be easily accessible and present in high enough numbers. Various molecules like antibodies peptides, nucleic acids, sugars and small vitamins can act as ligands for active targeting. Whereas passive targeting (shown in Figure ) relies on the natural tendency of certain molecules to accumulate in tumors due to their leaky blood vessels and poor lymphatic drainage and this is known as EPR effect (Enhanced permeation and retention effect). When tumors grow beyond a certain size, they don’t get enough oxygen causing some cells to die and new blood vessels to form. This allows nanoparticles to enter and stay in tumor (Malik et al., 2018).

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PHARMACOLOGICAL ACTIVITIES OF NANOPARTICLES

Antibacterial Activites

Metallic nanoparticles exhibit antibacterial property by disrupting the cell membrane and inhibton of protein synthesis (Sondi and Salopek-Sondi, 2004). Higher the concentration of nanoparticles higher the membrane permeability into the bacteria (Kasthuri et al., 2009). Silver nanoparticles are biosynthesized by a single step process using Citrus sinensis peel extract which act as reducing agent. Thisnanoparticles are active against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus (Kaviya et al., 2011).

Antifungal Activity

The Silver nanoparticle derived from plants have demonstrated evident membrane damage in candida species as well as disruption of fungal intracellular components ultimately leading to the destruction of cell function (Logeswari et al., 2025). Antifungal agents are associated with significant adverse effects, including hepatotoxicity and nephrotoxicity. The fungal cell wall is composed of a dense polymeric structure primarily made up of lipids and proteins. The silver nanoparticles have multifunctional activities against the fungus and disrupt the growth of fungal cells (Gardea-Torresdey et al., 2002).

Anti-Plasmodial Activity

The metallic silver nanoparticles efficiently control the malarial production. Active constituents like quinine, artemisinin and aromatic compounds used against resistant strains of malaria parasites (Jayaseelan et al., 2011).

Anticancer Activity

Cancer is the uncontrolled division of cells. This uncontrolled cell cycles can be disrupted using bio-based nanoparticles. Metallic nanoparticles are effective against different types of cancerous cells like Hep 2, HCT 116, and HeLa cell lines (Raghunandan et al., 2011). Nanoparticles helps in regulating the production of free radicals. Free radicals offer trigger cell proliferation and disrupt the normal cellular functions. This oxidative stress led to significant damage in biological systems affecting the integrity and stability of cells (Dipankar et al., 2012). Similarly, treatment of the MCF-7 cancer cell line with silver nanoparticles has maintained to the concentration of biomolecules withing the cells leading to regulation of cell metabolism (Das et al., 2011). Metallic nanoparticles consists of innovative implementations in aiding diagnosis and treatment of different types of cancers and retroviral diseases. The advent of biologically synthesized nanoparticles marks a step forward, offering the ability to target malignant deposits effectively while sparing normal cells from the damage (Suman et al., 2013).

Antiviral Activity

Bio-based nanoparticles have a promising alternative for treating and controlling the viral pathogens. This metallic silver nanoparticles serve as a potent broad spectrum antiviral agent, prevent the entry of viral pathogen in to the host cell. These nanoparticles posses multiple binding sites that attach to gp120 of the viral membrane and act as virucidal.

The results of various studies are integrated into the sections below: Types of Nanoparticles: NPs are classified into carbon, metal, ceramic, semiconductor, and polymeric types.Biological Activity: Plant-derived AgNPs (from leaves, seeds, or roots) show diverse activities, including antibacterial, anticancer, and antiviral properties.

CONCLUSION

Employing silver nanoparticles in biomedical research represents a cutting-edge development for aggressive breast cancer subtypes. Their unique physiochemical properties, such as high surface area and the ability to generate reactive oxygen species, allow AgNPs to offer enhanced therapeutic efficacy with lower systemic toxicity compared to conventional therapies.

ACKNOWLEDGEMENT

The authors are thankful to Shri Vishnu College of Pharmacy, Bhimavaram for providing the necessary facilities.

ABBREVIATIONS

AgNPs

Silver Nanoparticles

HER2

Human Epidermal Growth Factor Receptor-2

TNBC

Triple-negative breast cancer

FDA

Food and Drug Administration

ROS

Reactive Oxygen Species

PLGA

Poly(lactic-co-glycolic acid)

EPR

Enhanced permeation and retention effect

siRNA

Small interfering RNA

AuNPs

Gold nanoparticles

SWNTs

Single Walled Nano Tubes

MWNTs

Multiple walled carbon nanotubes

PNP

Polymer Nano Particle

RGONCs

Reduced Graphene Oxide Nanocomposites.

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

ETHICAL STATEMENT

These are not present in the sources as it is a review of existing literature

SUMMARY

Nanoparticles act as multifunctional vehicles that revolutionize healthcare by facilitating precise transport of bioactive compounds, improving drug solubility, and navigating biological barriers to elevate clinical outcomes.