Identification of a peptide for folate receptor alpha by phage display and its tumor targeting activity in ovary cancer xenograft

Liu, Xing; Xu, Yifeng; Sun, Keyong; Wang, Hong; Zhang, Fengguo; Zhou, Zihan; Zhang, Juan; Zhang, Fang; Caliskan, Bilgen; Zheng, Qiuju; Wang, Min

doi:10.1038/s41598-018-26683-z

Cited by 38 publications

(23 citation statements)

References 30 publications

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“…Thus, these results clearly confirmed the correct design of the peptide-based controlled delivery system created for this multifunctional silica-based nanodrug. In fact, the anti-proliferative activity enhancement of organotin metallodrug MSNs was achieved only in the case of interaction with tumor cells from breast adenocarcinoma that have been described overexpressing both folate receptor alpha and the cathepsin B enzyme, being this last the responsible of peptide cleavage and the metallodrug release [59,66,67]. Besides the antiproliferative activity, we decided to evaluate also the potential inhibition of migration ability of MDA-MB-231 cells by means of wound healing assay (Figure 7).…”

Section: In Vitro Characterization Of the Different Msn-based Multifumentioning

confidence: 99%

Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer

Paredes

Díaz-García

García-Almodóvar

et al. 2020

Cancers

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Three different multifunctional nanosystems based on the tethering onto mesoporous silica nanoparticles (MSN) of different fragments such as an organotin-based cytotoxic compound Ph3Sn{SCH2CH2CH2Si(OMe)3} (MSN-AP-Sn), a folate fragment (MSN-AP-FA-Sn), and an enzyme-responsive peptide able to release the metallodrug only inside cancer cells (MSN-AP-FA-PEP-S-Sn), have been synthesized and fully characterized by applying physico-chemical techniques. After that, an in vitro deep determination of the therapeutic potential of the achieved multifunctional nanovectors was carried out. The results showed a high cytotoxic potential of the MSN-AP-FA-PEP-S-Sn material against triple negative breast cancer cell line (MDA-MB-231). Moreover, a dose-dependent metallodrug-related inhibitory effect on the migration mechanism of MDA-MB-231 tumor cells was shown. Subsequently, the organotin-functionalized nanosystems have been further modified with the NIR imaging agent Alexa Fluor 647 to give three different theranostic silica-based nanoplatforms, namely, MSN-AP-Sn-AX (AX-1), MSN-AP-FA-Sn-AX (AX-2), and MSN-AP-FA-PEP-S-Sn-AX (AX-3). Their in vivo potential as theranostic markers was further evaluated in a xenograft mouse model of human breast adenocarcinoma. Owing to the combination of the receptor-mediated site targeting and the specific fine-tuned release mechanism of the organotin metallodrug, the nanotheranostic drug MSN-AP-FA-PEP-S-Sn-AX (AX-3) has shown targeted diagnostic ability in combination with enhanced therapeutic activity by promoting the inhibition of tumor growth with reduced hepatic and renal toxicity upon the repeated administration of the multifunctional nanodrug.

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Section: In Vitro Characterization Of the Different Msn-based Multifumentioning

confidence: 99%

Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer

Paredes

Díaz-García

García-Almodóvar

et al. 2020

Cancers

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“…The folate receptor is a cell surface glycoprotein receptor that is able to bind to folate with high affinity and mediate the unidirectional transport of folate into cells. Folate has been used for targeting cancers and tumors, as folate receptors are highly expressed on the surface of many types of tumors [ 42 ]. The high affinity of the folate receptor that is preferentially expressed in cancer cells is rarely expressed in normal cells.…”

Section: Introductionmentioning

confidence: 99%

“…The high affinity of the folate receptor that is preferentially expressed in cancer cells is rarely expressed in normal cells. This has allowed the development of the targeted delivery of anticancer drugs at the cancer at the tumor sites to maximize anticancer efficacy with minimizing side effects to healthy tissues [ 42 , 43 , 44 , 45 ]. The folate targeting of cancerous cells has been reported recently in many studies; e.g., L. Xing et al 2018 used folate targeting for ovary cancer cells, and found that folate receptor alpha (FRα) is overexpressed in ovary cancer cells [ 42 ].…”

Section: Introductionmentioning

confidence: 99%

Graphene Oxide–PEG–Protocatechuic Acid Nanocomposite Formulation with Improved Anticancer Properties

et al. 2018

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The treatment of cancer through chemotherapy is limited by its toxicity to healthy tissues and organs, and its inability to target the cancer site. In this study, we have designed an anticancer nanocomposite delivery system for protocatechuic acid (PCA) using graphene oxide–polyethylene glycol as the nanocarrier, and coated with folic acid (GO–PEG–PCA–FA) for targeting the cancer cells. The designed anticancer delivery system was found to show much better anticancer activity than the free drug PCA against liver cancer HEP-G2 cells and human colon cancer HT-29 cells; at same time, it was found to be less toxic to normal fibroblast 3T3 cells. The folate-coated anticancer delivery system was found to show better activity then the free drug and the uncoated anticancer delivery system. The in vitro release of the PCA was found to be sustained in human physiological pHs, i.e., blood pH 7.4 and intracellular lysosomal pH 4.8. These in vitro findings are highly encouraging for further in vivo evaluation studies.

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“…We show that synthetic TVRTSAE peptide binds SKOV3 cells in a dose-dependent manner and binds via the FRα since binding was inhibited when cells were pretreated with the FRα ligand folic acid. In similar studies, peptide MHTAPGWGYRLS was identified as a FRαspecific peptide using the same Ph.D-12 phage-display library for biopanning SKOV3 cells [42]. Peptide SWQIGGN was found to target HO8910 ovarian cancer cells in vitro, inhibiting cell viability, migration invasion…”

Section: Discussionmentioning

confidence: 99%

Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications

et al. 2020

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Oncolytic virotherapies (OV) based on human adenoviral (HAdV) vectors hold significant promise for the treatment of advanced ovarian cancers where local, intraperitoneal delivery to tumour metastases is feasible, bypassing many complexities associated with intravascular delivery. The efficacy of HAdV-C5-based OV is hampered by a lack of tumour selectivity, where the primary receptor, hCAR, is commonly downregulated during malignant transformation. Conversely, folate receptor alpha (FRα) is highly expressed on ovarian cancer cells, providing a compelling target for tumour selective delivery of virotherapies. Here, we identify high-affinity FRα-binding oligopeptides for genetic incorporation into HAdV-C5 vectors. Biopanning identified a 12-mer linear peptide, DWSSWVYRDPQT, and two 7-mer cysteine-constrained peptides, CIGNSNTLC and CTVRTSAEC that bound FRα in the context of the phage particle. Synthesised lead peptide, CTVRTSAEC, bound specifically to FRα and could be competitively inhibited with folic acid. To assess the capacity of the elucidated FRα-binding oligopeptides to target OV to FRα, we genetically incorporated the peptides into the HAdV-C5 fiber-knob HI loop including in vectors genetically ablated for hCAR interactions. Unfortunately, the recombinant vectors failed to efficiently target transduction via FRα due to defective intracellular trafficking following entry via FRα, indicating that whilst the peptides identified may have potential for applications for targeted drug delivery, they require additional refinement for targeted virotherapy applications.

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Identification of a peptide for folate receptor alpha by phage display and its tumor targeting activity in ovary cancer xenograft

Cited by 38 publications

References 30 publications

Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer

Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer

Graphene Oxide–PEG–Protocatechuic Acid Nanocomposite Formulation with Improved Anticancer Properties

Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications

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