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pH-Low Insertion Peptide (pHLIP) is a short, pH-responsive peptide capable of inserting across a cell membrane to form a transmembrane helix at acidic pH. pH-Low Insertion Peptide targets the acidic tumor microenvironment for tumors at early and metastatic stages with high specificity, used as a specific ligand. pH-Low Insertion Peptide successfully modify polylysine polymers to have the pH-responsive capability. pH-Low Insertion Peptide-based targeting of cancer presents an opportunity to monitor metabolic changes, and to selectively deliver imaging and therapeutic agents to tumors[1][2][3]. | [in vivo]
pH-Low Insertion Peptide (50 μM, a single tail vein injection, 4, 24, and 48 h) variants shows the pH-dependent tumor targeting and different blood clearance profiles, the overall tumor spatial distributions are identical in murine 4T1 xenograft mode[2].
pH-Low Insertion Peptide (10 μM, i.v., a single dose for 24 h) can clearly differentiate between regions of primarily tumor cells and nonmalignant stromal tissues, also accumulates the hypoxia marker Pimonidazole (HY-105129A) and relates to the production of acidic glucose metabolites in MMTV-Py MT mice[2].
pH-Low Insertion Peptide (0.2 μmol/kg, i.v., a single dose for 24 h) demonstrats excellent tumor targeting combined with PNA in mice seeded melanoma tumors[3].
| Animal Model: | Murine 4T1 xenograft model[2] | | Dosage: | 50 μM | | Administration: | a single tail vein injection, tumors collected at 4, 24, and 48 h after administration | | Result: | The spatial distribution and the intensity profiles of all pHLIPs in tumors were identical in murine 4T1 xenograft mode. |
| Animal Model: | FVB/N-Tg(MMTV-PyVT)634Mul/J transgenic female mice developed palpable mammary tumors at 12-15 weeks of age[2] | | Dosage: | 10 μM | | Administration: | i.v., a single dose for 24 h | | Result: | Clearly differentiated between regions of primarily tumor cells and nonmalignant stromal tissues. |
| Animal Model: | 6-week old C57BL/6 mice seeded melanoma tumors[3] | | Dosage: | 0.2 μmol/kg | | Administration: | intravenously injected via the retro-orbital sinus, a single dose for 24 h | | Result: | All the pH-Low Insertion Peptide-PNAs demonstrated excellent tumor targeting. |
| [References]
[1] Yushuang Wei, et al. pH-responsive pHLIP (pH low insertion peptide) nanoclusters of superparamagnetic iron oxide nanoparticles as a tumor-selective MRI contrast agent. Acta Biomater. 2017 Jun;55:194-203. DOI:10.1016/j.actbio.2017.03.046
[2] Adochite RC, et al. Targeting breast tumors with pH (low) insertion peptides[J]. Mol Pharm. 2014 Aug 4;11(8):2896-905. DOI:10.1021/mp5002526
[3] Svoronos AA, et al. Tumor-Targeted, Cytoplasmic Delivery of Large, Polar Molecules Using a pH-Low Insertion Peptide[J]. Mol Pharm. 2020 Feb 3;17(2):461-471. DOI:10.1021/acs.molpharmaceut.9b00883 |
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