# Targeted Lipid-Based Drug Delivery Systems for Lung Cancer Therapy
## 4 Surface Modification
### Lung Cancer and Targeting  
When trying to target lung cancer cells, it must be taken into account that there are some receptors which are overexpressed in these cells. Some typical examples are described below.  
* Epidermal growth factor receptor (EGFR): EGFR mutations have been identified to be associated with some lung cancers, more specifically responsible for non-small cell lung cancer [107]. This type of lung cancer is highly associated with higher mortality rates as well as metastatic behaviour [108] and poor chemosensitivity [109].
* Transferrin receptor: Cancer cells require an increased amount of iron when trying to grow and divide. Proteins such as transferrin (Tf) have been used in multiple delivery systems for cancer therapy, as the Tf receptor is overexpressed widely in various cancer cells such as lung cancer cells [110]. Tf enables the binding of two atoms of iron, making it ideal for targeting cancer cells [111].
* Polate receptor: This receptor has shown an increased selectivity in lung adenocarcinomas, making it an excellent target for this type of cancer [112].
* Cluster of differentiation 44 (CD44): It has been found that this glycoprotein is highly overexpressed on the surface of lung cancer cells [113] and it is associated with Fas protein expression [114], and therefore the initiation of the cancer cells' apoptosis process.
* Other receptors such as \(\alpha_{\mathrm{v}}\beta_{3}\) integrin receptor [115], luteinising hormone-releasing hormone (LHRH) receptor [116] or tyrosine kinase Axl receptor [117].  
Some typical examples of targeted moieties previously explored are shown in Figure 2 and include glycoproteins such as transferrin [110]; antibodies or antibody fragments to avoid the risk of inactivation of the antibody; aptamers such as A15 which has been identified as promising to target CD133 lung cancer cells [118]; and peptides such as CB5005 which inhibit the activation of transcription factor nuclear factor-xB [119]. Other types of ligands include hyaluronic acid, which has been used when targeting specific receptors (for example, glycoprotein CD44) that are overexpressed in most lung cancer cells [120], and folic acid, which has been widely used for functionalization when targeting folate receptors [121].  
Targeting any of these receptors can help in inhibiting lung cancer survival, any possible metastasis or tumour growth. During in vitro testing when developing a medicine,  
Figure 2: Different surface modifications for drug delivery systems which include PEGylation (**right** side) or not (**left** side).  
a few different lung cancer cell lines have been employed. A549 is the most common of them, as there are many studies in which an active pharmaceutical ingredient of a drug delivery system has been tested in this cell line which was first isolated in 1972 from the lung tissue of a 58-year old Caucasian man who suffered from bronchioalveolar lung cancer [122]. Another cell line that has been employed is H460 which, in comparison with A549, grows almost two times faster than A549 cells [123]. It is unique for studies because it is characterised as aggressive, since it has increased capacity for metastasis [124]. Another cell line employed is the H1299 cell line, also known as NCI-H1299 cell line, which has been isolated from the lymph node [125]. These cell lines are related to NSCLC. With regard to SCLC, H69, H466 and SHP-77 cell lines can be used. Both H69 and H466 cell lines have been introduced in 1982 by [PERSON] et al. [126], while SHP-77 has been isolated by [PERSON] and [PERSON] [127] from the upper lobe of the left lung of a 54-year old man.