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Article

A Small Peptide Increases Drug Delivery in Human Melanoma Cells

1
Department of Pharmacy Practice, Chapman University School of Pharmacy, Irvine, CA 92618, USA
2
Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, CA 92618, USA
3
Center for Developmental Therapeutics, Department of Chemistry, Department of Molecular Biosciences, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208, USA
4
Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
*
Authors to whom correspondence should be addressed.
Current address: Organometallic and Organometalloid Chemistry Department, National Research Centre, El Bohouth St., Dokki, Giza 12622, Egypt.
Current address: Department of Chemistry, Northern Michigan University, Marquette, MI 49855, USA.
Academic Editor: Gene L. Bidwell, III
Pharmaceutics 2022, 14(5), 1036; https://doi.org/10.3390/pharmaceutics14051036
Received: 8 April 2022 / Revised: 6 May 2022 / Accepted: 10 May 2022 / Published: 11 May 2022
(This article belongs to the Special Issue Prodrugs with Peptides as a Carrier for Cancer Treatment)
Melanoma is the most fatal type of skin cancer and is notoriously resistant to chemotherapies. The response of melanoma to current treatments is difficult to predict. To combat these challenges, in this study, we utilize a small peptide to increase drug delivery to melanoma cells. A peptide library array was designed and screened using a peptide array-whole cell binding assay, which identified KK-11 as a novel human melanoma-targeting peptide. The peptide and its D-amino acid substituted analogue (VPWxEPAYQrFL or D-aa KK-11) were synthesized via a solid-phase strategy. Further studies using FITC-labeled KK-11 demonstrated dose-dependent uptake in human melanoma cells. D-aa KK-11 significantly increased the stability of the peptide, with 45.3% remaining detectable after 24 h with human serum incubation. Co-treatment of KK-11 with doxorubicin was found to significantly enhance the cytotoxicity of doxorubicin compared to doxorubicin alone, or sequential KK-11 and doxorubicin treatment. In vivo and ex vivo imaging revealed that D-aa KK-11 distributed to xenografted A375 melanoma tumors as early as 5 min and persisted up to 24 h post tail vein injection. When co-administered, D-aa KK-11 significantly enhanced the anti-tumor activity of a novel nNOS inhibitor (MAC-3-190) in an A375 human melanoma xenograft mouse model compared to MAC-3-190 treatment alone. No apparent systemic toxicities were observed. Taken together, these results suggest that KK-11 may be a promising human melanoma-targeted delivery vector for anti-melanoma cargo. View Full-Text
Keywords: peptide; melanoma; uptake; tumor xenograft; targeted delivery; nNOS inhibitors peptide; melanoma; uptake; tumor xenograft; targeted delivery; nNOS inhibitors
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MDPI and ACS Style

Tong, S.; Darwish, S.; Ariani, H.H.N.; Lozada, K.A.; Salehi, D.; Cinelli, M.A.; Silverman, R.B.; Kaur, K.; Yang, S. A Small Peptide Increases Drug Delivery in Human Melanoma Cells. Pharmaceutics 2022, 14, 1036. https://doi.org/10.3390/pharmaceutics14051036

AMA Style

Tong S, Darwish S, Ariani HHN, Lozada KA, Salehi D, Cinelli MA, Silverman RB, Kaur K, Yang S. A Small Peptide Increases Drug Delivery in Human Melanoma Cells. Pharmaceutics. 2022; 14(5):1036. https://doi.org/10.3390/pharmaceutics14051036

Chicago/Turabian Style

Tong, Shirley, Shaban Darwish, Hanieh H.N. Ariani, Kate A. Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, and Sun Yang. 2022. "A Small Peptide Increases Drug Delivery in Human Melanoma Cells" Pharmaceutics 14, no. 5: 1036. https://doi.org/10.3390/pharmaceutics14051036

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