Design and Evaluation of Plasmonic/Magnetic Au-MFe2O4 (M-Fe/Co/Mn) Core-Shell Nanoparticles Functionalized with Doxorubicin for Cancer Therapeutics

Nanomedicine, the application of different nanostructures in the field of medicine which is aiming to revolutionize the health of humankind by a new developmental sector of nanopharmaceuticals [1]. The rapid evolution of nanomedicines has the huge probability to give many benefits when correlated to conventional medicines [2]. The major advantage of nanomedicine is to create a multifunctional platform using one nanostructure. Therefore, the various properties of nanostructures/NPs are exploited as tools in all aspect of medicine starting from diagnosis to treatment even at a molecular or cellular level for very rare and irremediable diseases [3]. Some of the applications of nanomedicine are as follows: drug delivery, therapies, in vivo imaging, in vitro diagnostics, biomaterials, active implants, bone substitute materials, dental restoratives, and antibiotic materials [4–6]. In the last two decades, significant progress has been made in the field of nanomedicine and nanobiotechnology, resulting in an enormous number of products. So, by the end of 2020, one-third of research patents and many start-up companies in the nanomedicine sector will engage in the biomedical applications [7]. To be specific, as of 2013, 1265 molecules are registered for clinical trials in which 789 were for nanomedicine applications or products [8]. Figure 1.1 represents the list of some of the important nanomedicine-related search terms in ClinicalTrials.​gov [9]. Therefore this proves the field of nanomedicine is booming at a faster rate. The global nanomedicine market was $1 trillion by 2015 but expected to be 100-fold in just 7 years [10].

Magnetic materials at nanoscale possess various biomedical applications due to their unique physical properties at the cellular and molecular levels of the biological interface. They are an efficient theranostic agent since they are considered to be good for therapeutic purposes, as well as for MR contrast imaging [1, 2]. They have been exploited for the diagnosis and treatment of cancer [3], cardiovascular diseases [4], and neurological diseases [5]. The size, shape, surface charge, surface chemistries, and composition can be tailored for such NPs so that their magnetic properties are improved and hence can be used proficiently for the theranostic purpose, both in vivo and in vitro [6].

The as-prepared NPs samples were characterized by a series of instruments to investigate their structure, morphology, and magnetic and optical properties.

Cancer, considered as a hallmark of diseases, is responsible for second most mortality and morbidity rates. The greatest discovery in the fundamental cancer biology has not been transformed into clinical therapeutics. There is a vast incongruity existing due to lack of translational medicine targeting towards the cancerous cells both temporally and spatially. Moreover, the drugs available possess a plethora of side effects and are incapable of circumventing the biophysical barriers posed by tumor microphysiology. The two nano-vectors, viz., drug-delivery and imaging have come to the rescue in such a debilitating condition of cancer therapeutics.

Cancer is the second leading disease which causes major mortality and morbidity worldwide [1]. In cancer therapy, it is crucial to increase the drug specificity and drug efficacy to minimize or completely eradicate significant side effects on patients [2]. Cancer nanotherapeutics overcome many serious drawbacks of chemotherapy such as nonspecific targeting, lower efficacy, insolubility of drug moieties in water, and oral bioavailability [3]. Accordingly, Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are exploited as an important nanomaterial for cancer detection as well as therapeutics [4]. Such magnetic nanoparticles (NPs) gained its momentum because of their single-domain ordering along with their large surface-to-volume ratio (providing large surface area for attachment of biological entities). Hence, this property makes them a suitable candidate as a contrast agent, drug-carrying cargo, and hyperthermal agent [5]. The doping of SPIONs with cobalt ions further enhances their magnetic property, thus forming CoFe₂O₄ nanokernels (Nks). These spinel ferrite Nks possess ca. 20–30 times higher magneto-crystalline anisotropy as compared to SPIONs; this increases the performance of materials for biomedical applications [6–8]. Specifically, these Nks are mostly used in biomedicine than any other spinel structure because of their enhanced magnetic property and large anisotropy [9]. The increased superparamagnetism makes them an efficient system for theranostics [10–12].

In the recent years, nanomedicine research drives to the designing of multifunctional nanoparticles for various biomedical applications in the field of diagnosis, treatment, and therapy. In particular, the functionalized magnetic nanoparticles (MNPs) have been widely exploited for several advantages which opens up many opportunities in the biomedicine and biotechnology field [1]. It is due to their uncommon chemical and physical features such as magnetic, electronic, and optical properties. And also, MNPs size, shape, surface modification, water dispersity, biocompatibility plays a major role in various applications. Some of the MNPs-based applications are magnetic resonance imaging (MRI), hyperthermia, and drug delivery [2–8]. The extensive studies has been carried out using iron oxides, but among ferrites manganese ferrite (Mf) is prominently used for various biomedical applications which is due to their property such as superparamagnetism, stability, and high magnetization. These properties have attracted the researchers to develop the Mf into multifunctional nanoparticles by various strategies such as core-shell (CSNPs) formation/bimetallic nanoparticles and surface modifications.

The work presented in this thesis aims to downgrade the side effects provoked by old-fashioned chemotherapy, by designing a versatile nanoparticle and demonstrating its capability of targeted delivery for a chemotherapeutic agent. Specifically, we have designed a multifunctional nanoparticle by employing iron oxide XFe₂O₄ (X = Fe/Mn/Co) (core)/gold (shell) based magneto/plasmonic core-shell nanoparticles using multiple gold iterations by seed-mediated method and used for cancer theranostic approaches such as