**1. Introduction**

For the innovative treatment of cancer, it is necessary to boost target-based cancer therapy, ensuring that it could differentiate between normal and cancer cells while targeting cells [1]. Targeted cancer therapies are far better than the conventional method [2]. Therefore, targeted cancer therapy enjoys lesser unwanted side effects and an excellent molecular mechanism, which promotes minimum toxicity

caused by chemotherapeutic drugs [3]. The rapid clearance from the body can be seen when the drug was administered in a higher tolerable dose, which ultimately leads to higher toxicity [4]. During targeted therapy, the drug could be modified to target biological transduction pathways and cellular factors. It also targets angiogenesis and apoptosis inducing molecules [5]. In recent years, several studies have been designed to investigate the effects of nanosized medicines inoperative targeting and diagnosis of cancer cells. Nanoparticles can possibly entrench drugs, theranostic agents, and genes [6]. It was also observed from the various research findings that, nanoparticular approach while drug targeting improves drug tolerability and bioavailability [7]. In formulation drug delivery, anchoring, fabricating, protection of payload from getting degradation by enzymes are possible [8]. The anchored nanoparticles can able to deliver a higher dose into tumor cells while bypassing the normal cells. The modified scaffold integration of nanoparticles facilitates biodistribution of specific drug delivery, which conjugates with ligands and eventually binds with tumor biomarkers [9]. Paul Ehrlich recently suggested a magic bullet, where two different targetings are possible with consistent therapeutic action [10]. In recent research articles and patents, it was often observed that many pharmaceutical carriers such as liposomes, micelles, polymeric nanoparticles designed from natural or synthetic sources were used to target chemotherapeutic medicaments in different cancer cells [11]. Many nanoparticles have passed phase II of the clinical trials stage. This suggests that effective active and passive targeting is possible, due to which greater specificity while selecting cancer target is achieved [12]. Nowadays, conjugation of antibodies, peptides, small chemical entities are versatile in delivering anticancer agents in the form of nanoparticle composite [13]. However, tumor targeting is not an easy job! Scientists are targeting tumors in three different mechanisms; (a) Where nanoparticles were pre-exposed with leaky vasculature of tumor cells and encountered with the reticuloendothelial system (RES) or enhanced permeability and retention (EPR) effects [14]. However, (b) active targeting is more advantageous, as inactive targeting, uncontrolled cell proliferative targeting of tumors, and pH and temperature-dependent targeting is possible. In physical targeting (c) pathological conditions such as pH and temperature play a key role. Nevertheless, targeting the tumor side also depends on the size of the nanoparticles. The nanoparticles, which are less than 7 nm, come under hydrodynamic diameters, easily passing through renal excretion [15]. The nanoparticles that are larger than 100 nm are eventually cleared from the circulation by the phagocytic system [16]. The nanoparticles' surface charge also plays a pivotal role, as the particles' cationic charge helps to facilitate internalization [17]. Sometimes surface addition of poly (sarcosine) and poly (ethylene glycol) [18] enhances the circulating half-life of the particles, on the other hand, preventing nanoparticles from getting engulfed by the reticuloendothelial system; by which accumulation of a certain amount of nanoparticles on the outer surface of the cancerous tissue is possible. To make nanoparticles more advanced, hooking ligands onto the nanoparticles' body facilitates internalization into cancer cells.

### **2. Molecular targets in cancer**

To target cancerous cells, it is essential to target molecular aberrations. Effective nanoparticular therapy for cancer targeting relies on the ability to targets such genetic alterations to provide significant clinical benefits [19]. Nowadays, scientists are more focused on targeting p53, ALK PIK3CA, KRAS, G-NAQ, MET, BRAF, EGFR, CKIT genes, and certain pathways, i.e., PI3K/Akt/mTOR, etc. [20].

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**Figure 1.**

*Targeted Cancer Therapy Using Nanoparticles and Antibody Fragments*

Ligands are a prerequisite for cancer. Recently, immunotoxin has obtained clinical approval from USFDA, and more than 100 ligand-targeted therapies are under clinical trials [21]. Newly developed phase-display techniques allow selective targeting with higher affinity. The bispecific antibodies and fusion proteins have been used for therapeutic purposes. Mostly the nanoreservior systems viz., niosomes, and polymeric nanoparticles are most suitable for ligand-based targeting [22]. However, pharmacokinetic behaviors and bio-distribution understanding of the molecules are still unknown. The principles of Ligands for cancer targeting can also be applied to the targeted delivery of gene medicines such as antisense oligo-

Most of the nanoparticles as specially lipid-based formulations and polymeric nanoparticles are emerging as the best carrier system to deliver the molecule in cancerous tissues [24]. Monoclonal antibodies and peptides are possibly the best carriers. The surface-bound ligands specifically bind to the target cells. The various techniques viz., covalent and non-covalent techniques help in effective active

Receptor based targeting is being focused on ensuring the accurate delivery of carriers to their desired location [25]. It allows targeting not only to a localized tumor but also to traveling cancerous cells. This ensures precise delivery. Due to the excessive expression of receptors, targeting becomes easy. Ligands carry out the

*Due to the active targeting, the nanoparticles are getting accumulated in the tumor site. Compered to nontargeted nanoparticles, actively targeted nanoparticles reach the tumor site with higher efficiency and through* 

*the endocytosis process, the nanocomposite triggers cancer cells death.*

*DOI: http://dx.doi.org/10.5772/intechopen.96550*

**4. Attachment of ligands to carriers**

targeting of cancer cells (**Figure 1**).

functionality through active targeting [26].

**5. Receptor approaches of drug targeting in cancer**

**3. Ligands for cancer targeting**

nucleotides [23].
