# Targeted Lipid-Based Drug Delivery Systems for Lung Cancer Therapy
## 4 Surface Modification
### Application of Targeted Lipid-Based Drug Delivery Systems in Lung Cancer Treatment  
Targeted drug delivery systems have shown enhanced tumour internalisation, diagnostic imaging and prolonged in vivo survival when compared to non-targeted drug delivery systems [128]. By surface functionalisation, key factors such as circulation time, cellular uptake, payload accumulation at the tumour site, bypassing lysosomal degradation and stimuli-responsive payload release at the desired site can be improved [129]. Most of the applications of surface modification for the treatment of lung cancer have been performed on liposomes and NLCs; however, similar approaches can be adopted to surface-functionalise other lipid-based formulations.  
When trying to target specific cells, and more specifically lung cancer cells, it is important to select the correct targeting moieties to achieve high selectivity in combination with minimal influence on healthy cells. This is important for the patients because when healthy cells remain intact, then side effects are minimal. Therefore, the targeting moiety should only attach on and kill the cancer cells and not the healthy ones. This is the reason why during any initial study in the laboratory a comparison of the susceptibilities of cancer cell lines and normal cell lines is required ahead of any animal testing or human clinical trials. Regarding the confirmation of ligand attachment onto the surface, various techniques have been used, such as transmission electron microscopy (TEM) [118], atomic force microscopy (AFM) [130], Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) [131], proton nuclear magnetic resonance (H-NMR) spectroscopy [88] and Fourier-transform infrared (FTIR) spectroscopy [88]. However, in some cases, there has been no difference between the modified and the non-modified liposomes when observed via TEM [119].  
There have been a few studies where the surface modification of liposomes and NLCs has been investigated (Table 2). Most of the studies have used a specific cell line, i.e., A549. They are characterised as botriploid human alveolar basal epithelial cells and they are generally used during in vitro studies mostly for type II pulmonary epithelial cells and for lung adenocarcinoma cells [132]. Other cell lines that are presented in the same table include the NCI-H460 cell line as well as the MRC5-SV2 cell line. The latter cell line was derived from the MRC5 lung cell line by transformation with the SV40 virus, a known oncogenic virus [133]. The responses of a cancer cell line should be compared with those of a corresponding healthy cell line, for example (in the case of the MRC5-SV2), the MRC5 cell line, which was derived from the healthy lung tissue of a 14-week old foetus which was removed from a 27-year old woman in 1966 as reported by [PERSON] et al. [134].  
There are some receptors which are overexpressed normally in lung cancer cells. These include the transferrin [89] receptor, folate receptor [135] as well as EGFR [136]. For these types of receptors, the cell culture studies are performed directly in the wide-type cell lines. However, in other cases, cells have to be engineered or have their growth conditions modified to overexpress the receptor of interest; an example is the carbonic anhydrase receptor, for which the cells have to be incubated under hypoxia in order for this receptor to be overexpressed [131].