TMTP1, a Novel Tumor-homing Peptide, Specifically Targets Hematological Malignancies and Their Metastases

TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignant in situ and metastatic lesions, and even micro-metastases. In this study, TMTP1 was assessed for its ability to specifically target the malignant hematopoietic cells and metastatic lesions of hematological malignancies. FITC-TMTP1 was chemically synthesized. Immunofluorescence assay and competitive test were carried out to determine the specific binding capacity of TMTPl to hematological malignant cell lines, including HL60, k562, SHI-1, Jurkat, Raji, El-4 and umbilical cord blood mononuclear cells. Mononuclear cells were isolated from the bone marrow of healthy subjects and patients with chronic myeloid leukemia. Then the cells were co-clutured with TMTP1 or scrambled peptides and the binding and affinity of TMTP1 peptide to the primary cells of hematological malignancies were flow cytometrically analyzed. The binding speci-ficity of TMTP1 to target hematological malignancies was measured in vivo by intravenous injection of FITC-conjugated TMTP1 into El-4 lymphoma-bearing mice. The results showed that TMTP1 specifi-cally bound to the cells of a series of hematological malignancies, including HL60, k562, Jurkat, Raji , El-4 and chronic myeloid leukemia primary cells but not to bone marrow mononuclear cells from healthy subjects. By contrast, TMTP1 could bind to the metastatic foci of lymphoma originating from the EL-4 cell line while the scrambled peptide failed to do so. Moreover, the occult metastases could be identified, with high specificity, by detecting FITC-TMTP1. We are led to conclude that TMTP1, as a novel tumor-homing peptide, can serve as a marker for primary malignant and metastatic lesions for the early diagnosis of hematological malignances and a carrier of anticancer drugs for cancer treatment.

Formulated nano-liposomes for reversal of cisplatin resistance in NSCLC with nucleus-targeting peptide

Cell membrane-engineered nano-delivery systems have evolved as a promising strategy to enhance drug bioavailability,offering an alternative for reversing drug resistance in cancer therapy.Herein,a formulated nano-liposome that fabricated by hybridizing cisplatin-resistant A549 cell line(A549/cis)cancer cell membrane and phospholipids for co-delivery of cisplatin and nuclear protein zeste homolog 2(EZH2)-targeting peptide EIP103,referred to as cLCE,was developed.In vitro results indicated that the formulated nano-liposome can efficiently inhibit A549/cis cancer cell invasion and metastasis through the down-regulation of Ncadherin and vimentin proteins.Mechanistic studies demonstrated that the reduction of nerve growth factor receptor(NGFR)levels and the increase of peroxisome proliferator-activated receptorγ(PPARγ)levels achieved by EIP103 may contribute to the reversal of cisplatin resistance.In vivo results demonstrated that the encapsulation of both cisplatin and EIP103 within cLCE leads to increased intratumoral accumulation and prolonged survival in A549/cis cancer-bearing mice as compared to the individual drugs alone.This can be attributed to the enhanced tumor homing capability of cLCE achieved through the presence of inherited membrane proteins derived from A549/cis cells.Taken together,this study may provide a highly promising therapeutic strategy to improve clinical treatments for cisplatin-resistance non-small-cell lung cancer(NSCLC)as well as other malignant cancers.