Table 1.
FR-targeted nanoformulations designed for cancer treatment.
| Formulation | Cancer type/Activity | Stage | Reference | ||
|---|---|---|---|---|---|
| Folic acid conjugated nanomedicines | Folic acid-cytotoxic drug conjugates | Folic acid-maytansinoid conjugates | Marked antiproliferative effect in ovarian, colon, nasopharyngeal carcinoma, lung, and cervical cancer (FR positive). No-activity in melanoma and breast cancer (FR negative) | Pre-clinical | [27,28] |
| Folic acid-5-fluorouracil conjugates | Antitumor effect in colon cancer that overexpresses FRs | Pre-clinical | [30] | ||
| Folic acid-methotrexate-arabinogalactan conjugates | Cytotoxic effect in leukemia models | Pre-clinical | [31] | ||
| Folic acid-SB-T-1214 conjugates | Cytotoxic effect in blood, breast, and ovarian carcinomas overexpressing FRs. | Pre-clinical | [32] | ||
| Folic acid-mitomicyn conjugates | Cytotoxic activity in lung adenocarcinoma models that overexpress FR | Pre-clinical | [33] | ||
| Folic acid-bleomicyn conjugates | Cytotoxic effect in ovarian cancer (FR positive) | Pre-clinical | [34] | ||
| Folic acid-camptothecin conjugates | Cytotoxic effect in FR positive cancer cells of the mouth | Pre-clinical | [37] | ||
| Folic acid-polyethylene glycol-rhaponticin conjugates | Potent cytotoxic effect in FR positive epithelial and KB cancer cells. No-activity in FR-negative breast cancer cells | Pre-clinical | [38] | ||
| Folic acid conjugated to a vinca alkaloid | Potent effect in ovarian cancer models (FR positive). This formulation is under clinical research | Clinical trial | [39] | ||
| Folic acid conjugated to solubilizing peptide moiety (BMS-753493) | Phase I clinical studies in ovarian, colorectal, lung, and mammary tumors overexpressing FRs. An objetive anticancer response was not detected. | Clinical trial | [76] | ||
| Folic acid conjugated to tubulysin (EC-1456) | Potent cytotoxic effect in vintafolide resistant FR-positive KB cancer cells. Phase I clinical studies in non-small lung cancer and ovarian cancer | Clinical trial | [77] | ||
| Folic acid-Paclitaxel conjugates | No higher effect compared with unconjugated drugs in colon cancer cells that overexpress FR | Pre-clinical | [40] | ||
| Folic acid-polyethylene glycol-cisplatin conjugates | No higher effect compared with unconjugated drugs in lung cancer cells that overexpress FR. However, a higher uptake was detected | Pre-clinical | [41] | ||
| Folic acidfunctionalized nanoparticles | Folic acid-coated pH-sensitive liposomes loaded with doxorubicin | Cytotoxic effect in breast cancer models (FR positive) | Pre-clinical | [45] | |
| Folic acid-coated pH-sensitive liposomes loaded with paclitaxel | Pre-clinical | [46,47] | |||
| Folic acid-coated non-pH-sensitive liposomes loaded with doxorubicin | Pre-clinical | [49] | |||
| Folic acid-coated silica mesoporous nanoparticles loaded with topotecan | Cytotoxic effect in retina cancer models (FR positive) | Pre-clinical | [52] | ||
| Folic acid-coated silica mesoporous nanoparticles loaded with cisplatin | Cytotoxic effect in cervical cancer models (FR positive) | Pre-clinical | [51] | ||
| Folic acid-coated silica mesoporous nanoparticles loaded with doxorubicin | Pre-clinical | [50] | |||
| Folic acid-coated Poly(lactic-co-glycolic acid) nanoparticles loaded with cisplatin | Pre-clinical | [53] | |||
| Folic acid-Alendronate-coated Poly(lactic-co-glycolic acid) nanoparticles loaded with paclitaxel | Cytotoxic effect in non-small lung cancer overexpressing FR | Pre-clinical | [54] | ||
| Folic acid-coated Poly(lactic-co-glycolic acid) nanoparticles loaded with paclitaxel and cisplatin | Non-coated and folic acid coated nanoparticles showed a similar tumor growth inhibition in FR-positive lung tumo models developed in mice | Pre-clinical | [55] | ||
| Folic acid-functionalized iron oxide condensed colloidal magnetic clusters containing doxorubicin | Cytotoxic activity in FR-positive triple-negative breast cancer | Pre-clinical | [56] | ||
| Folic acid-functionalized iron oxide nanoparticles | Cytotoxic activity in FR-positive cervical cancer | Pre-clinical | [57] | ||
| Folic acid-coated liposomes loaded with BIM-S plasmid | Anticancer effect in non-small lung cancer. The formulations were designed for tumor associated macrophages | Pre-clinical | [61] | ||
| Folic acid-functionalized-liposomes loaded with doxycycline | Pre-clinical | [63] | |||
| Folic acid-coated chitosan nanoparticles loaded with signaling transducers and activators of transcription 3 | Anticancer effect in Lewis lung adenocarcinoma. The formulations were designed for tumor associated macrophages | Pre-clinical | [64] | ||
| Anti-FR-monoclonal antibodies coupled nanoformulations | Antibody- drugconjugates | Farletuzumab conjugated with eribulin | Anticancer effect in non-small lung cancer overexpressing FR | Clinical trial | [68] |
| Anti-FRα-monoclonal antibody-maytansinoid conjugate (mirvetuximab soravtansine) | Higher anticancer activity in ovarian and non-small lung carcinomas overexpressing FRα. Several clinical trials are ongoing to evaluate its efficacy as monotherapy or in combination with chemo and other immmunotherapeutic drugs in ovarian cancer patients | Clinical trial | [69,70,71,72,73,74] | ||
| FR-targeted-nanoparticles | Antibody-conjugated gold-coated magnetite nanoparticles | Anticancer effect in triple-negative breast cancer overexpressing FR | Pre -clinical | [75] | |