# Targeted Lipid-Based Drug Delivery Systems for Lung Cancer Therapy
## 4 Surface Modification
### Ligands Used for Liposome Surface Modification  
Regarding the surface modification of liposomes, various ligands have been previously investigated as described in Table 2. According to [PERSON] et al., the attachment of A15 aptamer has provided sustained release of doxorubicin, as well as a decreased growth in the cancer cells [118]. A15 has been identified as a promising ligand to bind onto CD133, which is a marker widely involved in the NSCLC. It has also improved the therapeutic efficiency; this could be possibly due to the amount of drug delivered to the target cells. When the A549 cell line was used, a superior inhibition of cell growth was observed when the surface-modified liposomes were tested in comparison with the drug itself and the liposomes without A15 aptamer [118]. Another study showed that carbonic anhydrase IX, an antibody controlled by hypoxia-inducible factor, successfully improved the uptake of the surface-modified liposomes, leading to increased cytotoxicity by killing more cancer cells compared to free triptolide and non-modified liposomes. Cellular uptake from the A549 cell line was increased by the targeted liposomes compared to the non-targeted ones [131]. The delivery of triptolide via dual ligand modified liposomes consisting of anti- carbonic anhydrase IX and CPP33 was also investigated by [PERSON] et al. [55]. The in vitro tests showed that the modified liposomes successfully inhibited cancer cell proliferation in the A549 cell line. Compared to endotracheal administration, pulmonary delivery exhibited higher anticancer efficacy without expressing any toxicity [55]. Aspartate-conjugated polyoxyethylene stearate has also been studied as a targeting moiety for ATB\({}^{0+}\) and it has shown promising results. ATB\({}^{0+}\) is an amino acid transporter which is suitable for targeting cancer cells. Compared to plain docetaxel, the modified liposomes exhibited higher delivery of docetaxel within the cells and increased antitu \begin{table}
\begin{tabular}{c c c c c c c c c} \hline \hline
**System** & **Drug** & **Cell Line** & **SM Material** & **Ligand** & **Receptor** & **Size (nm)** & **Test** & **Ref.** \\ \hline Liposomes & Docetaxel & A549 & DSPE-PEG2000 & A15 & CD133+ cells & 116.5 & TEM & [118] \\  & Triptolide & A549 & DSPE-PEG-MAL & Anti-carbonic anhydrase & Carbonic & 160.1 & SDS-PAGE & [131] \\  & Docetaxel & A549 & N/A & Aspartate- & ATB0,+ & 99.5 & AFM & [137] \\  & & & polyoxyethylene & & & & & \\  & Paclitaxel & A549 & Pluronic P123 & Chitosan & Not specified & 75 & TEM & [138] \\  & & & & oligosaccharide with & & & & \\  & & & & Pluronic P123 (CF50) & & & & & \\  & & & & & & & & \\  & & & & & & & & \\  & & & & & & & & \\  & & & & & & & & \\  & & & & & & & & \\ \hline NLCs & Sunitinib & A549 & StearyJamine & Biotin & Biotin receptor & 125.50 & H-NMR and & [88] \\  & & & & & & & FTIR & \\  & & & & & & & & \\  & & & & & & & & \\  & & & & & & & & \\  & & & & & & & & \\  & & & & & & & & \\  & & & & & & & & \\  & & & & & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Targeted lipid-based drug delivery system. This table describes various drug delivery systems, i.e., liposomes and NLCs that have been investigated, the drug involved, the cell line tested, the surface modification (SM) materials, the ligands and the targeted receptors as well as the particle size and the test that has been performed to identify the attachment of the ligand on the outer surface of the delivery system. mour potency against the A549 cell line [137]. A new biomaterial consisting of chitosan oligosaccharidesacharide [145] and Pluronic P123 was attached on the surface of liposomes, which delivered paclitaxel successfully to the A549 cell line and inhibited its growth. [PERSON] et al. studied the delivery of rapamycin through folic acid modified liposomes [139]. The folate receptor is widely overexpressed in various cancer cells, including lung cancer cells. Folic acid can attach on the folate receptors, and this is why it can be chosen as a targeting moiety.