**6. Receptors**

### **6.1 EGFR**

EGFR is a glycoprotein spanning across cell membranes. It is a target for Epidermal Growth Factor [28]. It initiates a signaling pathway leading to cell proliferation and mitosis. This is overexpressed in breast, colon, head and neck, ovarian tumors, and renal and glioma. The binding of antibodies against this receptor reduces cell proliferation. Many researchers prepared drug-loaded vesicles to target EFGR, which increased the drug's efficacy more than 10-fold [29]. Recently, cancer varieties like colorectal, lung, head, and neck carcinoma showed resistance to EGFR targeting due to mutations in the gene causing inhibition of activation and hence signaling.

#### **6.2 Interleukin receptors**

As interleukin receptors are majorly expressed, they are essential as a target for delivery. Among many varieties, types-3, 4, 6, 11, 13 & 16 were investigated as a target. The complex of ligand and receptor is taken inside the cell and hence helps cell growth and proliferation. But an overexpression may cause resistance to apoptosis and malignant growth (**Table 1**)**.**


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*Targeted Cancer Therapy Using Nanoparticles and Antibody Fragments*

Various researchers used many ways to target IL receptors and obtained positive results such as reduced proliferation, enhanced uptake of carriers, decreased tumor volume, as well as accumulation and entry into the tumor as well as increased survival. This is not a full-proof strategy as blocking signaling of one type may be compensated with another type. And if the interleukins are blocked, it hinders the

Folate receptor is a glycoprotein present on the external cell surface. It is rich in cystine content. It has three subtypes- α, β and γ [30]. It is responsible for the entry of folic acid into cell, which is important for nucleic acid synthesis. The α subtype is overexpressed in breast, lung, colon cancer, and mesothelioma [31]. According to studies from many researchers, positive results such as a reduced tumor volume, nuclear delivery of therapeutic moieties, increased survival of cells, upregulation of cell death were observed. As folate receptors are present in the body on abundant sites, the selectivity may not always be achieved. Also, there are no animal models

Integrins are proteins that bind to the extracellular matrix and promote cell binding to tissues. Due to this action, this receptor is essential in the progression and metastasis of tumors. 'RGD motif' is a polypeptide chain important for binding and has been majorly exploited as a drug target [32]. Targeting the RGD motif has advantages such as improved survival, reduced tumor mass, and tumor growth inhibition. A major drawback of integrin targeting is diseases such as progressing

CD receptors initiate tumor development and can self-renew, overexpression of ABC, dormant. These features give tumor characteristics such as resistance, recurrence, and metastasis. Blocking these receptors prevents metastasis. CD subtypes 14, 22, 36, 44, 133 have been explored as drug targets for delivery. Targeting CD-44 receptors on cells allowed delivery into even the resistant tumors and showed

These are nuclear receptors binding to the hormone estrogen. Estradiol acts as a transcription factor and controls cell growth. Estrogen helps in the development of sexual and reproductive functions, initiation and forming of lungs, mammary glands, and prostate gland. These receptors are excessively expressed in the majority of types of breast cancers, making it an ideal target. Initially, hormone analogs were used as ligands to target, but the binding strength was not optimal due to the modified structure of hormones. Also, another drawback was excessive RES uptake of such liposomes, which was overcome by formulating stealth liposomes. These

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

functioning of the immune system.

for therapeutic advantages or toxicity profiling.

**6.3 Folate receptors**

**6.4 Integrin receptors**

lymphadenopathy [33].

enhanced cytotoxicity [34].

**7.2 Estrogen receptors**

**7. Receptors to inhibit metastasis**

**7.1 The cluster of differentiation receptors**

formulations showed reduced tumor volume [35].

**Table 1.** *Type of interleukin.* *Targeted Cancer Therapy Using Nanoparticles and Antibody Fragments DOI: http://dx.doi.org/10.5772/intechopen.96550*

Various researchers used many ways to target IL receptors and obtained positive results such as reduced proliferation, enhanced uptake of carriers, decreased tumor volume, as well as accumulation and entry into the tumor as well as increased survival. This is not a full-proof strategy as blocking signaling of one type may be compensated with another type. And if the interleukins are blocked, it hinders the functioning of the immune system.

#### **6.3 Folate receptors**

*Advances in Precision Medicine Oncology*

deleted) [27].

**6. Receptors**

**6.1 EGFR**

signaling.

**Interleukin type**

**6.2 Interleukin receptors**

and malignant growth (**Table 1**)**.**

IL-6 Ovarian cancer

IL-13 Head and neck cancer

**Overexpressed in**

IL-4 Glioblastoma, ovarian cancer, lung cancer, breast cancer IL-3 Chronic Myelogenous leukemia, acute myeloid leukemia blast

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 functionalization through active targeting (this has to be

EGFR is a glycoprotein spanning across cell membranes. It is a target for Epidermal Growth Factor [28]. It initiates a signaling pathway leading to cell proliferation and mitosis. This is overexpressed in breast, colon, head and neck, ovarian tumors, and renal and glioma. The binding of antibodies against this receptor reduces cell proliferation. Many researchers prepared drug-loaded vesicles to target EFGR, which increased the drug's efficacy more than 10-fold [29]. Recently, cancer varieties like colorectal, lung, head, and neck carcinoma showed resistance to EGFR targeting due to mutations in the gene causing inhibition of activation and hence

As interleukin receptors are majorly expressed, they are essential as a target for delivery. Among many varieties, types-3, 4, 6, 11, 13 & 16 were investigated as a target. The complex of ligand and receptor is taken inside the cell and hence helps cell growth and proliferation. But an overexpression may cause resistance to apoptosis

**80**

**Table 1.**

*Type of interleukin.*

Folate receptor is a glycoprotein present on the external cell surface. It is rich in cystine content. It has three subtypes- α, β and γ [30]. It is responsible for the entry of folic acid into cell, which is important for nucleic acid synthesis. The α subtype is overexpressed in breast, lung, colon cancer, and mesothelioma [31]. According to studies from many researchers, positive results such as a reduced tumor volume, nuclear delivery of therapeutic moieties, increased survival of cells, upregulation of cell death were observed. As folate receptors are present in the body on abundant sites, the selectivity may not always be achieved. Also, there are no animal models for therapeutic advantages or toxicity profiling.

#### **6.4 Integrin receptors**

Integrins are proteins that bind to the extracellular matrix and promote cell binding to tissues. Due to this action, this receptor is essential in the progression and metastasis of tumors. 'RGD motif' is a polypeptide chain important for binding and has been majorly exploited as a drug target [32]. Targeting the RGD motif has advantages such as improved survival, reduced tumor mass, and tumor growth inhibition. A major drawback of integrin targeting is diseases such as progressing lymphadenopathy [33].

## **7. Receptors to inhibit metastasis**

#### **7.1 The cluster of differentiation receptors**

CD receptors initiate tumor development and can self-renew, overexpression of ABC, dormant. These features give tumor characteristics such as resistance, recurrence, and metastasis. Blocking these receptors prevents metastasis. CD subtypes 14, 22, 36, 44, 133 have been explored as drug targets for delivery. Targeting CD-44 receptors on cells allowed delivery into even the resistant tumors and showed enhanced cytotoxicity [34].

#### **7.2 Estrogen receptors**

These are nuclear receptors binding to the hormone estrogen. Estradiol acts as a transcription factor and controls cell growth. Estrogen helps in the development of sexual and reproductive functions, initiation and forming of lungs, mammary glands, and prostate gland. These receptors are excessively expressed in the majority of types of breast cancers, making it an ideal target. Initially, hormone analogs were used as ligands to target, but the binding strength was not optimal due to the modified structure of hormones. Also, another drawback was excessive RES uptake of such liposomes, which was overcome by formulating stealth liposomes. These formulations showed reduced tumor volume [35].
