## 3 Results
### Targeted Drug Delivery  
#### 3.2.1 Active Targeting  
Active targeting involves functionalizing the surface of nanoparticles with specific ligands, which is particularly advantageous in cancer treatment where overexpression of certain receptors is common. Various ligands, including antibodies, peptides, aptamers, and small molecules, have been explored for their ability to recognize and bind to specific receptors on target cells. In hepatocellular carcinoma, receptors such as sialoglycoprotein, transferrin, folate, CD44 antigen, and integrins bind to complementary ligands on nanocarriers [51]. These targeting ligands promote receptor-mediated endocytosis of the drugs into liver tumor cells, enhancing the selective delivery of chemotherapeutic to the tumor, thus improving treatment efficacy while minimizing damage to healthy tissues [7]. The CD44 receptor, a transmembrane glycoprotein, serves as the primary receptor for hyaluron. Hyaluronan is a polysaccharide and a key component of the extracellular matrix, alongside collagen. The interaction between CD44 and hyaluron influences cancer cell phenotypic behaviors, such as tumor progression, metastasis, and cell proliferation. The literature also indicates that the tumor microenvironment should be considered in disease management, as it significantly influences the development of hepatocellular carcinoma. Based on this interaction, liposomes functionalized with hyaluronic acid (HA) and/or PEG have demonstrated promising therapeutic potential in hepatocellular carcinoma. These nanocarriers exhibit favorable physicochemical properties and are efficiently internalized by cells that overexpress CD44, such as Huh7 cells. Additionally, PEG can modulate interactions with immune cells, particularly tumor-associated macrophages, while reducing off-target uptake by tumor cells with low CD44 expression. Thus, dual-targeting strategies addressing both tumor cells and the immunological components of the tumor microenvironment are emerging as promising approaches to enhance therapeutic efficacy in the treatment of hepatocellular carcinoma, as demonstrated in the study conducted by [PERSON] et al. [52]. The asialoglycoprotein receptor (ASGPR), also known as the galactose receptor, has drawn attention due to its highly specific expression on hepatocytes and near its absence in other tissues. ASGPR mediates nanoparticle internalization through clathrin-mediated endocytosis when nanoparticles are surface-decorated with galactose or N-acetylgalactosamine [53]. Among the delivery systems exploiting this mechanism, galactosylated chitosan (Gal-CS) nanoparticles--produced by grafting lactobionic acid onto chitosan--have demon \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Nanoparticle** & **Application** & **Dignostic** & **Model** & **Technique** & **Efficacy Outcomes** & **Reference** \\
**Classification** & **Type** & **Agent** & & & Strong CT/MRI & \\  & & & & & contrast (Yb3+); high & \\  & & & & & UCL signal; & \\ Upconversion & & & In vitro (HepG2); & & pH/NIR-triggered & \\  & & Yb3+-doped & In vivo & CT, MRI, UCL & dual drug release & \\  & & & (HCC-bearing & imaging, PTT, & (DOX, HCPT); tumor & \\  & & & core & mice) & confocal & localization; high & \\  & & & (Preclinical study) & microscopy & photothermal & \\  & & & & & efficiency; significant & \\  & & & & tumor inhibition; & \\  & & & & & minimal systemic & \\  & & & & toxicity & \\ \hline \hline \end{tabular} Abbreviations: MRI—Magnetic Resonance Imaging; CT—Computed Tomography; TEM—Transmission Electron Microscopy; DLS—Dynamic Light Scattering; UCL—Upconversion Luminescence; PET—Positron Emission Tomography; AST—Aspartate Aminotransferase; PLT—Platelets.  
\end{table} 
Table 2: _Cont._strated considerable potential in HCC therapy. Researchers have successfully loaded these carriers with various therapeutic agents, including doxorubicin, 5-fluorouracil, gemcitabine, and triptolide, for targeted treatment of liver cancer [54]. In their study, [PERSON] et al.