Table 5.
Summary of various nanoformulations using folic acid as a potential target to deliver drugs to HCC tumor cells.
| Targeting Moiety | Nanocarrier | Cargo Carried by Nanocarrier | In Vitro and/or In Vivo Studies and Results |
|---|---|---|---|
| Folic acid [262] | Pluronic F127 nanomicelles | Silibinin | In vitro cytotoxicity in HepG2 cells indicated that the viability of cells treated with conjugated NPs was significantly less than unconjugated NPs |
| Folic acid [263] | Mn-ZnS quantum dots with chitosan biopolymer | 5-Fluorouracil | In vitro drug release and in vivo sub-chronic toxicity assay and anti-4T1 breast cancer study indicated a controlled release behavior in vitro and accumulation of NPs in the tumor of the tumor-bearing mice |
| Folic acid [264] | Casein micelles | Berberine and diosmin | In vivo cytotoxicity and uptake studies using HepG2 cells supported with in vivo antitumor efficacy using DENA-induced HCC mouse model demonstrated superior cytotoxicity and cellular uptake in vitro along with increased antitumor efficacy in vivo |
| Folic acid and/or bevacizumab (dual targeting) [265] | Carbon dots | Gadolinium (imaging nanoprobe) | In vitro cytotoxicity assay, fluorescent imaging, and cellular uptake using Hepa1-6 and L929 cells indicated low toxicity with improved sensitivity and specificity as an ideal fluorophore nanosystem |
| Folic acid [266] | Human serum albumin nanoparticles | Sorafenib | In vitro cell viability assay, cellular uptake, and apoptosis analysis using BEL-7402 cells along with in vivo antitumor efficacy and safety evaluation and tissue distribution study using BEL-7402 xenograft model and pharmacokinetic study confirmed enhanced cytotoxicity, increased safety, and notably enhanced sorafenib accumulation in tumor tissues in vivo |
| Folic acid [267] | Quantum dots | 5-fluorouracil | In vitro cellular uptake using HepG2 cells and in vivo antitumor efficacy, toxicity, and biodistribution study using SMMC-7721 xenograft model indicated reduced cytotoxicity compared to free drug in vitro and enhanced tumor suppression in vivo |
| Folic acid [268] | ZIF-8 nanoparticles | Doxorubicin | In vitro cytotoxicity using HepG2 cells showed higher anti-cancer efficiency as a targeted therapy |
| Folic acid and Transferrin [269] | Graphene oxide DDS | Doxorubicin | In vitro cytotoxicity using SMMC-7721 cell line indicated that the double target drug delivery system exhibited controlled drug release, no toxicity, and better inhibitory effect on HCC cells |
| Adamantanyl-folic acid [270] | Ternary nanoassembly | Pheophorbide | In vitro cellular uptake, photodynamic therapy, and apoptosis assay in MCF-7 and PC3 cells demonstrated increased cellular uptake and improved phototoxicity |
| PEG-Folic acid [271] | Gold nanocages | Anti-miR-181b | In vitro cellular uptake and cytotoxicity assay using SMMC-7721 cells accompanied with in vivo biodistribution and antitumor effect in SMMC-7721 xenograft model indicated efficient cargo delivery in vitro and suppressing tumor growth and significantly reducing tumor volumes in vivo |
| Folic acid [272] | Liposomes | HSV-TK suicide gene | In vitro cellular uptake and cell viability using SMMC-7721, HepG2, and HL-7702 cells and in vivo tumor and tissue distribution imaging using Bel-7402 xenograft model and antitumor efficacy using Bel-7402 xenograft model demonstrated highly tumor-specific imaging and excellent antitumor activity devoid of any systemic toxicity |
| Folic acid [106] | Selenium nanoparticles | HES5 siRNA | In vitro cellular uptake, cytotoxicity, and apoptosis assay using HepG2 and Lo2 cell lines along with in vivo biodistribution and antitumor efficacy using HepG2 xenograft model indicated higher cellular uptake, enhanced gene silencing efficiency, and increased cytotoxicity in vitro. NPs conjugated with FA showed increased antitumor efficacy and low toxicity compared to unconjugated NPs |
| Folic acid [256] | Drug delivery vehicle | Fluorescein | In vitro cytotoxicity and apoptosis assay using N1S1 and U937 cell lines supported with in vivo biodistribution using N1S1 cell-induced murine model. Results indicated increased specific uptake due to cell surface folate receptors |
| Folic acid [273] | Porphyrin nanoparticles | Gadolinium | In vitro biotoxicity and imaging capability using HepG2 cells and in vivo biotoxicity and imaging capability in embryonic and larval zebrafish demonstrated excellent MRI capability both in vitro and in vivo due to its strong affinity for folate receptor on HCC tumor cells |
| Folic acid [274] | pH-sensitive nanoparticles | Triptolide | In vitro cytotoxicity and cellular uptake using Bel-7404 cells and in vivo distribution and antitumor effect using Bel-7404 xenograft model indicated that the pH-sensitive NPs increased cellular uptake mitigating the significant toxicity of triptolide |