¹Department of Chemistry, Sri Aurobindo College, University of Delhi, New Delhi-110017, India.

²Department of Chemistry, Motilal Nehru College, University of Delhi, New Delhi-110021, India

³School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India

Corresponding author email: abhijeetjmi@gmail.com

Article Publishing History

INTRODUCTION

Novel metal nanoparticles show outstanding unique physiochemical and biological characteristics. Noble metal nanoparticles can be used in different areas such as biosensor, catalysis, antibacterial, anticancer, antimalarial and antiviral (Marin et al., 2015). In the present decade, fabrication of novel metal nanoparticles can be achieved via various procedures (Mousavi et al., 2016). Although, chemical based methods are the widely applied methods for the fabrication of nanostructure. Though, chemical processes cannot prevent the use or generation of by-product of hazardous chemicals (Celik et al., 2017). However, metallic nanoparticles are extensively used for medical biotechnology including human contacting areas.  Therefore, there is an increasing demand to develop environmentally sustainable methods of nanoparticle fabrication without uses of toxic ingredients (Saratale et al., 2018, Iravani et al., 2020).

Among several metal nanoparticles, silver and gold, have been studied and are useful in different fields such as antimicrobials, biosensors, drug and gene delivery etc. In addition, Ag and Au nanoparticles have a unique surface plasmon resonance (SPR) absorption in the UV-vis region. However, now a days bimetallic and trimetallic nanoparticles have also used due to unique properties for biomedical applications such as cancer treatment. (Ali et al., 2020, Ravi et al., 2020) There are different types of metal nanoparticles are described below:

Based on morphology: NPs can also be classified on the basis of their morphologies such as aspect ratio and sphericity. The high aspect ratio nanomaterials of various design such as nano-sphere and nanocubes having low aspect ratio while nanowires having high aspect ratio (You et al., 2017, Singh et al., 2020).

Based on constituents and structures: NPs are either of single or multiple moieties, they may be of organic-inorganic hybrid nature (more than one constituent).  The structures of the NPs depend on the nature of these constituents, which are used as reaction precursors during their preparation.  Based on nature of constituents, NPs can also be classified as:

Organic NPs: Organic moieties such as lipid, polymers and natural/synthetic organic materials are covered in the class of organic NPs (ONPs) (Rizwan et al., 2017). They are applied in the form of liposomes, metal organic frameworks, polymeric micelles of polyacrylate, polycarbonate, polyester etc. (Zakharova et al., 2017). There are many FDA approved ONPs, which are used as controlled release agents to deliver the desired moiety to the target site. For instance, leuprorelin acetate (synthetic gonadotropin release hormone, GnRH) depot releases in 6 months, is used for the cure of prostate cancer (Hebenstreit et al.,2020).

Polymeric NPs: The polymeric nanoparticles (PNPs) are categorized as colloidal particles of nano scale, which are derived from various polymers including natural, semisynthetic and synthetic polymers (Mohammadi et al., 2020). Some of these NPs are pH and temperature sensitive and prepared from biocompatible and biodegradable polymers.

Dendrimers: Dendrimers are three dimensions globular molecules, mono-dispersed with repeating units having large number of functional groups present on their surfaces. The word “dendrimer” was elicited from Greek word “dendron” that symbolizes a tree (Sapra et al., 2019). They are highly dense and less viscous due to their extensive branching (Patel et al., 2020).

Liposomes: Liposomes are colloidal nanomaterial having vesicular structure. Liposomes are usually made up of phospholipids while few are made up of phosphatidylcholine (Daraee et al., 2016). In liposomes, the double phospholipid layers have an internal aqueous cavity. They are amphiphilic nature and exhibits biocompatibility (Ding et al., 2020).

Inorganic NPs: Inorganic NPs are characterized as particles of nano-sized prepared by the applications of inorganic moieties like metalloid and metal (Tabesh et al., 2017). They possess specific and unique properties, which mainly depend on their sizes. Special properties of inorganic NPs such as versatile physical, chemical, optical and magnetic makes them available for various applications in water treatment to biomedical (Zhao et al., 2018). NPs like gold and silver have strong absorbance and high electron density and particles like iron oxide has great magnetic characteristics. From literature, it can be concluded that Metallic NPs are particularly, prepared at optimum temperature, have no effect on changing the pH and are non-toxic to healthy cells (Yilmaz et al., 2018). Moreover, the novel inventions of magnetic metallic NPs introduced them in environmental applications. (Ravi et al.2019) The use of magnetic NPs particularly in adsorption technology may promise to advance the technique through the post adsorption magnetic separation of adsorbents (Arabkhani et al.,2020). All these features of metallic NPs are size dependent and in many cases, they are considered as best materials. These metallic NPs can be classified as:

Zerovalent (ZV) metallic NPs: ZV Metallic NPs have significant importance due to their distinguished properties in nanoscale compared to their bulk state. They are employed in several applications such as sensing, catalysis, adsorption and imaging due to their unique optical property, sensitivity and larger surface area along with significant photo-stability (Hai et al., 2018). Several methods are employed for the synthesis of these NPs, such as chemical, biological, electrochemical, photolytic, etc. Among them, the most significant and widely used synthetic method is the wet chemical method (chemical precipitation or chemical reduction) and biological. ZV Metallic NPs are synthesized in their uncharged state (zero-valent) through the reduction of their metal precursor using a common reducing agent i.e., chemical reduction and/or plant extraction method (Reverberi et al., 2018).

The ZV metallic NP appears different in different conditions, e.g. ZV gold NPs in bulk state is yellow but its aqueous dispersion in nanoscale ranges from red or violet. Similarly, ZV silver NPs looks yellow in their aqueous nanoscale formulation while ZV iron NPs appear in greenish color under aerobic conditions. These changes in appearance are mainly attributed to the mutual oscillations of the electrons in conduction band caused due to the light exposure of a specific wavelength and power. This is a well-known phenomenon termed as localized surface plasmon resonance (LSPR), which occurs due to the collective oscillations of electrons in an externally applied electric field (Feng et al., 2020).

Metal NPs as cancer treatment agent: Cancer is considered as one of the biggest challenges faced by the medical researchers in recent time. The high cost and strong side effects of available options limits their applications for cancer treatment. Further, the timely diagnosis and prognosis of cancer is still a difficult task (Mishra et al., 2012, Restifo et al., 2016) Moreover, the approaches usually used for cancer treatment such as surgery, radiation and chemotherapy have considerable harmful effects (Gill et al., 2014). Thus, there is a crucial need for application of new feasible and novel methods (non-invasive and minimally invasive) for the early diagnosis and therapy of cancers (Li et al., 2015). In this regard, bimetallic nanoparticles (BNPs) and trimetallic nanoparticles (TNPs) have come up as a potential candidate for the cancer therapeutics, which has given a new field of research in the form of cancer nanomedicine. BNPs and TNPs provide the basis for the continuous and targeted release of the anticancer agent at a pace and at a venue to overcome the issues of standard diagnostic and therapeutic methods (Senapati et al.,2018, Sivamaruthi et  al., 2019). Fig 1. shows illustration of applications of different metal nanoparticles against various cancers.

Figure 1: Graphical representation of metal nanoparticles and their different applications against various cancer types.

On this account, several researchers have made their effort to synthesize BNP and TNPs also investigated their cancer therapeutic activities. For instance, wang et al. have reported rapid and single-pot approach for the synthesis of Cu/Au/Pt TNPs. The TNPs showed high catalytic behaviour and strong plasmonic absorption in the NIR-I bio window (650-950 nm). Because of these properties, the synthesized Cu/Au/Pt TNPs was used for the application in biosensing and cancer theranostics. The trimetallic nanoparticles have also been used for dye removal and cancer treatment. For instance, Basavegowda et al. (2017) have synthesized trimetallic Fe-Ag-Pt nanoparticles via ultra-sonication. These trimetallic alloys nanostructures have exhibited excellent catalytic efficiency and have also been used for other applications. Ahmad et al. (2019) formulated trimetallic Au/Pt/Ag nanoparticle based nanofluids by green microwave assisted successive chemical reduction method and used this to check the antibacterial activity and compared to these of monometallic Au and bimetallic Au/Pt nanofluid. Liang et al. (2018) immobilized trimetallic Cu-Ni-Co nanoparticles onto the pores of the metal-organic framework by a simple but unique solvent evaporation approach and compared to their bimetallic and monometallic equivalents. These investigations revealed that the Cu-Ni-Co trimetallic catalysts display superior catalytic activity.

Recently, Gu et al. (2019) have synthesized carbon dots embedded bimetallic ZrHf-based metal-organic framework (CDs@ZrHf-MOF). The synthesized bimetallic NP was used to assess to differentiate human epidermal growth factor receptor-2 (HER2) and living HER2-overexpressed MCF-7 cells. Ma et al. (2015) fabricated extremely sensitive electrochemical immune sensor for the sensing of bladder cancer biomarker i.e. nuclear matrix protein 22 (NMP22). This sensor contain reduced graphene oxide–tetraethylene pentamine (rGO–TEPA) and trimetallic AuPdPt NPs. Sharma et al. (2018) have designed Zr₂Ni₁Cu₇ trimetallic nanoparticle and its composite with Si₃N₄. Both the composite and TNPs were subjected to photo-degradation of methylene blue under visible light. Pradhan et al. (2007) have reported the synthesis and characterization of manganese ferrite based magnetic liposomes. The synthesized materials was further applied for hyperthermia cancer treatment.

Table 1. Anticancer Applications of Metal Nanoparticles

S.N.	Name of Metal Nanoparticles	Size of Nanoparticles (nm)	Application against Cancer Cells/Tumors	Ref.
1	Silver (Ag)	4.99-25.83	MCF-7	(Jhang et al., 2016)
2	Silver (Ag)	22–85	MCF-7, PC-3, A549, HCT-116	(Abd-Elnaby et al., 2016)
3	Silver (Ag)	10-80	HepG2, A549	(Rajeshkumar et al., 2016)
4	Silver (Ag) Gold (Au)	24-150	HCT-116	(Kuppusamy et al., 2016)
5	Gold (Au)	50-100	HT-29	(Bai et al., 2018)
6	Gold (Au)	10-40	HeLa	(Patil et al., 2019)
7	Silver (Ag)	10-20	DU154, A549, MCF-7, A431	(Singh et al., 2020)
8	Silver (Ag)	24-54	MCF-7	(Kiran et al., 2020)
9	Gold (Au)	5-10	MCF-7	(Munawer et al., 2020)
10	Silver (Ag)	15.45	MCF-7	(Nawaz et al., 2020)

CONCLUSION

Thus, based on above literature survey, it can be concluded that the metal NPs could be used as anticancer agent. However, the scant work has been reported on their applications in cancer treatment. Tireless efforts are being made to use metal NPs in the field of cancer management, and further, it was observed that metal NPs have an enormous capability to improve the efficacy of cancer therapeutics. In addition, animal model and clinical human trials are necessary part for the practical applications for these nanoparticles.

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