Active Targeted Nanoformulations Via Folate Receptors: State of the Art and Future Perspectives

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Jan 21

PMID 35056911

Authors

Cristina Martin-Sabroso

Ana Isabel Torres-Suarez

Mario Alonso-Gonzalez

Ana Fernandez-Carballido

Ana Isabel Fraguas-Sanchez

Affiliations

Soon will be listed here.

Abstract

In normal tissues, the expression of folate receptors is low and limited to cells that are important for embryonic development or for folate reabsorption. However, in several pathological conditions some cells, such as cancer cells and activated macrophages, overexpress folate receptors (FRs). This overexpression makes them a potential therapeutic target in the treatment of cancer and inflammatory diseases to obtain a selective delivery of drugs at altered cells level, and thus to improve the therapeutic efficacy and decrease the systemic toxicity of the pharmacological treatments. Two strategies have been used to achieve this folate receptor targeting: (i) the use of ligands with high affinity to FRs (e.g., folic acid or anti-FRs monoclonal antibodies) linked to the therapeutic agents or (ii) the use of nanocarriers whose surface is decorated with these ligands and in which the drug is encapsulated. This manuscript analyzes the use of FRs as a target to develop new therapeutic tools in the treatment of cancer and inflammatory diseases with an emphasis on the nanoformulations that have been developed for both therapeutic and imaging purposes.

Citing Articles

Mirvetuximab Soravtansine in solid tumors: A systematic review and meta-analysis.

Rehim S, Yuan S, Wang H PLoS One. 2024; 19(12):e0310736.

PMID: 39729462 PMC: 11676571. DOI: 10.1371/journal.pone.0310736.

MicroRNA Nobel Prize: Timely Recognition and High Anticipation of Future Products-A Prospective Analysis.

Niazi S, Magoola M Int J Mol Sci. 2024; 25(23.

PMID: 39684593 PMC: 11641023. DOI: 10.3390/ijms252312883.

Folate-engineered chitosan nanoparticles: next-generation anticancer nanocarriers.

Kesharwani P, Halwai K, Jha S, Mughram M, Salman Almujri S, Almalki W Mol Cancer. 2024; 23(1):244.

PMID: 39482651 PMC: 11526716. DOI: 10.1186/s12943-024-02163-z.

Revealing tumor cells and tissues with high selectivity through folic acid-targeted nanofluorescence probes responsive to acidic microenvironments.

Li J, He H, Liu S, Li X, Wu F Front Oncol. 2024; 14:1404148.

PMID: 38933449 PMC: 11199542. DOI: 10.3389/fonc.2024.1404148.

Application of High-Z Nanoparticles to Enhance Current Radiotherapy Treatment.

Jackson N, Cecchi D, Beckham W, Chithrani D Molecules. 2024; 29(11).

PMID: 38893315 PMC: 11173748. DOI: 10.3390/molecules29112438.

References

Frigerio B, Bizzoni C, Jansen G, Leamon C, Peters G, Low P . Folate receptors and transporters: biological role and diagnostic/therapeutic targets in cancer and other diseases. J Exp Clin Cancer Res. 2019; 38(1):125. PMC: 6417013. DOI: 10.1186/s13046-019-1123-1. View

Moore K, Borghaei H, OMalley D, Jeong W, Seward S, Bauer T . Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α-targeting antibody-drug conjugate, in patients with solid tumors. Cancer. 2017; 123(16):3080-3087. PMC: 6896318. DOI: 10.1002/cncr.30736. View

Bilthariya U, Jain N, Rajoriya V, Jain A . Folate-conjugated albumin nanoparticles for rheumatoid arthritis-targeted delivery of etoricoxib. Drug Dev Ind Pharm. 2013; 41(1):95-104. DOI: 10.3109/03639045.2013.850705. View

Wang Y, Zhang C, Li H, Zhu G, Bao S, Wei S . Synthesis, characterization and in vitro anticancer activity of the biomolecule-based coordination complex nanotubes. J Mater Chem B. 2020; 3(2):296-305. DOI: 10.1039/c4tb01135j. View

Thomas T, Goonewardena S, Majoros I, Kotlyar A, Cao Z, Leroueil P . Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis. Arthritis Rheum. 2011; 63(9):2671-80. PMC: 3168725. DOI: 10.1002/art.30459. View

Fraguas-Sanchez A, Martin-Sabroso C, Fernandez-Carballido A, Torres-Suarez A . Current status of nanomedicine in the chemotherapy of breast cancer. Cancer Chemother Pharmacol. 2019; 84(4):689-706. DOI: 10.1007/s00280-019-03910-6. View

Herzog T, Kutarska E, Bidzinsk M, Symanowski J, Nguyen B, Rangwala R . Adverse Event Profile by Folate Receptor Status for Vintafolide and Pegylated Liposomal Doxorubicin in Combination, Versus Pegylated Liposomal Doxorubicin Alone, in Platinum-Resistant Ovarian Cancer: Exploratory Analysis of the Phase II PRECEDENT.... Int J Gynecol Cancer. 2016; 26(9):1580-1585. DOI: 10.1097/IGC.0000000000000806. View

Maurer A, Elsinga P, Fanti S, Nguyen B, Oyen W, Weber W . Imaging the folate receptor on cancer cells with 99mTc-etarfolatide: properties, clinical use, and future potential of folate receptor imaging. J Nucl Med. 2014; 55(5):701-4. DOI: 10.2967/jnumed.113.133074. View

Moore K, Martin L, OMalley D, Matulonis U, Konner J, Perez R . Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study. J Clin Oncol. 2016; 35(10):1112-1118. PMC: 5559878. DOI: 10.1200/JCO.2016.69.9538. View

10.

Vaitilingam B, Chelvam V, Kularatne S, Poh S, Ayala-Lopez W, Low P . A folate receptor-α-specific ligand that targets cancer tissue and not sites of inflammation. J Nucl Med. 2012; 53(7):1127-34. DOI: 10.2967/jnumed.111.099390. View

11.

Mentch S, Locasale J . One-carbon metabolism and epigenetics: understanding the specificity. Ann N Y Acad Sci. 2015; 1363:91-8. PMC: 4801744. DOI: 10.1111/nyas.12956. View

12.

Chen S, Liu T, Chuang C, Chen H, Chiang W, Chiu H . Alendronate/folic acid-decorated polymeric nanoparticles for hierarchically targetable chemotherapy against bone metastatic breast cancer. J Mater Chem B. 2020; 8(17):3789-3800. DOI: 10.1039/d0tb00046a. View

13.

He L, Marneros A . Doxycycline inhibits polarization of macrophages to the proangiogenic M2-type and subsequent neovascularization. J Biol Chem. 2014; 289(12):8019-28. PMC: 3961635. DOI: 10.1074/jbc.M113.535765. View

14.

Buist M, Kenemans P, den Hollander W, Vermorken J, Molthoff C, Burger C . Kinetics and tissue distribution of the radiolabeled chimeric monoclonal antibody MOv18 IgG and F(ab')2 fragments in ovarian carcinoma patients. Cancer Res. 1993; 53(22):5413-8. View

15.

Konner J, Bell-McGuinn K, Sabbatini P, Hensley M, Tew W, Pandit-Taskar N . Farletuzumab, a humanized monoclonal antibody against folate receptor alpha, in epithelial ovarian cancer: a phase I study. Clin Cancer Res. 2010; 16(21):5288-95. DOI: 10.1158/1078-0432.CCR-10-0700. View

16.

Naumann R, Coleman R, Burger R, Sausville E, Kutarska E, Ghamande S . PRECEDENT: a randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2013; 31(35):4400-6. DOI: 10.1200/JCO.2013.49.7685. View

17.

Silva J, Fernandes R, Oda C, Ferreira T, Botelho A, Melo M . Folate-coated, long-circulating and pH-sensitive liposomes enhance doxorubicin antitumor effect in a breast cancer animal model. Biomed Pharmacother. 2019; 118:109323. PMC: 7104811. DOI: 10.1016/j.biopha.2019.109323. View

18.

Fisher R, Siegel B, Edell S, Oyesiku N, Morgenstern D, Messmann R . Exploratory study of 99mTc-EC20 imaging for identifying patients with folate receptor-positive solid tumors. J Nucl Med. 2008; 49(6):899-906. DOI: 10.2967/jnumed.107.049478. View

19.

Leamon C, Reddy J, Vlahov I, Kleindl P, Vetzel M, Westrick E . Synthesis and biological evaluation of EC140: a novel folate-targeted vinca alkaloid conjugate. Bioconjug Chem. 2006; 17(5):1226-32. DOI: 10.1021/bc060145g. View

20.

Birrer M, Moore K, Betella I, Bates R . Antibody-Drug Conjugate-Based Therapeutics: State of the Science. J Natl Cancer Inst. 2019; 111(6):538-549. DOI: 10.1093/jnci/djz035. View