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Peptide-based targeted therapeutics and apoptosis imaging probes for cancer therapy
Vadevoo, Sri Murugan Poongkavithai,Gurung, Smriti,Khan, Fatima,Haque, Md. Enamul,Gunassekaran, Gowri Rangaswamy,Chi, Lianhua,Permpoon, Uttapol,Lee, Byungheon Springer-Verlag 2019 Archives of Pharmacal Research Vol.42 No.2
Peptides as multifunctional players in cancer therapy
Vadevoo Sri Murugan Poongkavithai,Gurung Smriti,Lee Hyun-Su,Gunassekaran Gowri Rangaswamy,Lee Seok-Min,Yoon Jae-Won,Lee Yun-Ki,Lee Byungheon 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Peptides exhibit lower affinity and a shorter half-life in the body than antibodies. Conversely, peptides demonstrate higher efficiency in tissue penetration and cell internalization than antibodies. Regardless of the pros and cons of peptides, they have been used as tumor-homing ligands for delivering carriers (such as nanoparticles, extracellular vesicles, and cells) and cargoes (such as cytotoxic peptides and radioisotopes) to tumors. Additionally, tumor-homing peptides have been conjugated with cargoes such as small-molecule or chemotherapeutic drugs via linkers to synthesize peptide–drug conjugates. In addition, peptides selectively bind to cell surface receptors and proteins, such as immune checkpoints, receptor kinases, and hormone receptors, subsequently blocking their biological activity or serving as hormone analogs. Furthermore, peptides internalized into cells bind to intracellular proteins and interfere with protein–protein interactions. Thus, peptides demonstrate great application potential as multifunctional players in cancer therapy.
Gunassekaran, Gowri Rangaswamy,Hong, Chae-Moon,Vadevoo, Sri Murugan Poongkavithai,Chi, Lianhua,Guruprasath, Padmanaban,Ahn, Byung-Cheol,Kim, Ha-Jeong,Kang, Tae Heung,Lee, Byungheon IPC Science and Technology Press 2018 Biomaterials Vol.159 No.-
<P><B>Abstract</B></P> <P>Adoptive transfer of cytotoxic T lymphocytes (CTLs) has been used as an immunotherapy in melanoma. However, the tumor homing and therapeutic efficacy of transferred CTLs against melanoma remain unsatisfactory. Interleukin-4 receptor (IL-4R) is commonly up-regulated in tumors including melanoma. Here, we studied whether IL-4R-targeted CTLs exhibit enhanced tumor homing and therapeutic efficacy against melanoma. CTLs isolated from mice bearing melanomas were non-genetically engineered with IL4RPep-1, an IL-4R-binding peptide, using a membrane anchor composed of dioleylphosphatidylethanolamine. Compared to control CTLs, IL-4R-targeted CTLs showed higher binding to melanoma cells and <I>in vivo</I> tumor homing. They also exerted a more rapid and robust effector response, including increased cytokine secretion and cytotoxicity against melanoma cells and enhanced reprogramming of M2-type macrophages to M1-type macrophages. Moreover, IL-4R-targeted CTLs efficiently inhibited melanoma growth and reversed the immunosuppressive tumor microenvironment. These results suggest that non-genetically engineered CTLs targeting IL-4R have potential as an adoptive T cell therapy against melanoma.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
HaqueMohammadEnamul,Fatima Khan,Lianhua Chi,Smriti Gurung,Sri Murugan Poongkavithai Vadevoo,박랑운,김동규,김상균,이병헌 대한암학회 2019 Cancer Research and Treatment Vol.51 No.3
Purpose This study was carried out to identify a peptide that selectively binds to kidney injury molecule- 1 (KIM-1) by screening a phage-displayed peptide library and to use the peptide for the detection of KIM-1–overexpressing tumors in vivo. Materials and Methods Biopanning of a phage-displayed peptide library was performed on KIM-1–coated plates. The binding of phage clones, peptides, and a peptide multimer to the KIM-1 protein and KIM-1–overexpressing and KIM-1–low expressing cells was examined by enzyme-linked immunosorbent assay, fluorometry, and flow cytometry. A biotin-peptide multimer was generated using NeutrAvidin. In vivo homing of the peptide to KIM-1–overexpressing and KIM- 1–low expressing tumors in mice was examined by whole-body fluorescence imaging. Results A phage clone displaying the CNWMINKEC peptide showed higher binding affinity to KIM-1 and KIM-1–overexpressing 769-P renal tumor cells compared to other phage clones selected after biopanning. The CNWMINKEC peptide and a NeutrAvidin/biotin-CNWMINKEC multimer selectively bound to KIM-1 over albumin and to KIM-1–overexpressing 769-P cells and A549 lung tumor cells compared to KIM-1–low expressing HEK293 normal cells. Colocalization and competition assays using an anti–KIM-1 antibody demonstrated that the binding of the CNWMINKEC peptide to 769-P cells was specifically mediated by KIM-1. The CNWMINKEC peptide was not cytotoxic to cells and was stable for up to 24 hours in the presence of serum. Whole-body fluorescence imaging demonstrated selective homing of the CNWM-INKEC peptide to KIM-1–overexpressing A498 renal tumor compared to KIM- 1–low expressing HepG2 liver tumor in mice. Conclusion The CNWMINKEC peptide is a promising probe for in vivo imaging and detection of KIM-1– overexpressing tumors.
Chi, L.,Na, M.H.,Jung, H.K.,Vadevoo, S.M.P.,Kim, C.W.,Padmanaban, G.,Park, T.I.,Park, J.Y.,Hwang, I.,Park, K.U.,Liang, F.,Lu, M.,Park, J.,Kim, I.S.,Lee, B.H. Elsevier Science Publishers 2015 Journal of controlled release Vol.209 No.-
A growing body of evidence suggests that pathological lesions express tissue-specific molecular targets or biomarkers within the tissue. Interleukin-4 receptor (IL-4R) is overexpressed in many types of cancer cells, including lung cancer. Here we investigated the properties of IL-4R-binding peptide-1 (IL4RPep-1), a CRKRLDRNC peptide, and its ability to target the delivery of liposomes to lung tumor. IL4RPep-1 preferentially bound to H226 lung tumor cells which express higher levers of IL-4R compared to H460 lung tumor cells which express less IL-4R. Mutational analysis revealed that C1, R2, and R4 residues of IL4RPep-1 were the key binding determinants. IL4RPep-1-labeled liposomes containing doxorubicin were more efficiently internalized in H226 cells and effectively delivered doxorubicin into the cells compared to unlabeled liposomes. In vivo fluorescence imaging of nude mice subcutaneously xenotransplanted with H226 tumor cells indicated that IL4RPep-1-labeled liposomes accumulate more efficiently in the tumor and inhibit tumor growth more effectively compared to unlabeled liposomes. Interestingly, expression of IL-4R was high in vascular endothelial cells of tumor, while little was detected in vascular endothelial cells of control organs including the liver. IL-4R expression in cultured human vascular endothelial cells was also up-regulated when activated by a pro-inflammatory cytokine tumor necrosis factor-α. Moreover, the up-regulation of IL-4R expression was observed in primary human lung cancer tissues. These results indicate that IL-4R-targeting nanocarriers may be a useful strategy to enhance drug delivery through the recognition of IL-4R in both tumor cells and tumor endothelial cells.