Enhanced Therapeutic Effect of Optimized Melittin-dKLA, a Peptide Agent Targeting M2-like Tumor-Associated Macrophages in Triple-Negative Breast Cancer

Kim, Soyoung; Choi, Ilseob; Han, Ik-Hwan; Bae, Hyunsu

doi:10.3390/ijms232415751

Cited by 10 publications

(5 citation statements)

References 70 publications

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“…A conjugated peptide-peptide fused with melittin (melittin 8-26) and the pro-apoptotic peptide d(KLAKLAK)2 (dKLA) could inhibit tumor growth and reduce mortality in a mouse model bearing 4T1 TNBC in vivo ( 82 ). Melittin-dKLA 8-26 treatment reduces the numbers of M2-like tumor-associated macrophages, which are the main components of TME and involved in the regulation of tumor invasion, angiogenesis, growth, migration and metastasis ( 71 , 175 ).…”

Section: Discussionmentioning

confidence: 99%

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The current landscape of the antimicrobial peptide melittin and its therapeutic potential

Zhang,

Sun,

et al. 2024

Front. Immunol.

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Melittin, a main component of bee venom, is a cationic amphiphilic peptide with a linear α-helix structure. It has been reported that melittin can exert pharmacological effects, such as antitumor, antiviral and anti-inflammatory effects in vitro and in vivo. In particular, melittin may be beneficial for the treatment of diseases for which no specific clinical therapeutic agents exist. Melittin can effectively enhance the therapeutic properties of some first-line drugs. Elucidating the mechanism underlying melittin-mediated biological function can provide valuable insights for the application of melittin in disease intervention. However, in melittin, the positively charged amino acids enables it to directly punching holes in cell membranes. The hemolysis in red cells and the cytotoxicity triggered by melittin limit its applications. Melittin-based nanomodification, immuno-conjugation, structural regulation and gene technology strategies have been demonstrated to enhance the specificity, reduce the cytotoxicity and limit the off-target cytolysis of melittin, which suggests the potential of melittin to be used clinically. This article summarizes research progress on antiviral, antitumor and anti-inflammatory properties of melittin, and discusses the strategies of melittin-modification for its future potential clinical applications in preventing drug resistance, enhancing the selectivity to target cells and alleviating cytotoxic effects to normal cells.

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Section: Discussionmentioning

confidence: 99%

“…Melittin-mediated inhibition on the tumor invasion of breast cancer have been reported ( 81 , 82 ). Breast cancer is the second most lethal cancer among women.…”

Section: Antitumor Potential Of Melittinmentioning

confidence: 99%

The current landscape of the antimicrobial peptide melittin and its therapeutic potential

Zhang,

Sun,

et al. 2024

Front. Immunol.

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“…PEGylation was performed to stabilize the new molecule. The resulting PEG-melittin-dKLA8-26 peptide showed excellent effect in the treatment of a mouse model of triplenegative breast cancer and its metastasis compared to the previously tested melittin-dKLA peptide (108).…”

Section: Finding a Safe Way To Use Bee Venom Componentsmentioning

confidence: 93%

Bee Venom - Friend or Enemy

Pudelka,

Janovska,

Malis

et al. 2024

Mil. Med. Sci. Lett.

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Increasing resistance to antibiotics, adverse effects of standard anti-cancer or anti-inflammatory treatments, or tumour types resistant to these treatments are leading to a search for alternatives. One of these is the use of natural products, such as bee venom, which have the same or better effect than these standard products. Bee venom has been used to treat a number of diseases for thousands of years. However, a significant obstacle remains the risk of severe allergic reactions, which can be caused by some of the more than 100 substances contained in the venom. Therefore, intensive research is currently underway to investigate not only the actual use of bee venom or its components in the above areas, but also ways to prevent these adverse effects.

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“…This modified fragment showed a potent therapeutic effect against cancers by depleting CD206+ M2 cells in Triple-Negative Breast Cancer. ( Kim et al, 2022 ). The works of Bae’s group indicated the potential of MEL fragment in TAM targeting treatment.…”

Section: Targeting Tams: a Promising Spot Owing To Their Vital Roles ...mentioning

confidence: 99%

Tumor-associated macrophages in nanomaterial-based anti-tumor therapy: as target spots or delivery platforms

Zheng,

Jiang,

et al. 2023

Front. Bioeng. Biotechnol.

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Targeting tumor-associated macrophages (TAMs) has emerged as a promising approach in cancer therapy. This article provides a comprehensive review of recent advancements in the field of nanomedicines targeting TAMs. According to the crucial role of TAMs in tumor progression, strategies to inhibit macrophage recruitment, suppress TAM survival, and transform TAM phenotypes are discussed as potential therapeutic avenues. To enhance the targeting capacity of nanomedicines, various approaches such as the use of ligands, immunoglobulins, and short peptides are explored. The utilization of live programmed macrophages, macrophage cell membrane-coated nanoparticles and macrophage-derived extracellular vesicles as drug delivery platforms is also highlighted, offering improved biocompatibility and prolonged circulation time. However, challenges remain in achieving precise targeting and controlled drug release. The heterogeneity of TAMs and the variability of surface markers pose hurdles in achieving specific recognition. Furthermore, the safety and clinical applicability of these nanomedicines requires further investigation. In conclusion, nanomedicines targeting TAMs hold great promise in cancer therapy, offering enhanced specificity and reduced side effects. Addressing the existing limitations and expanding our understanding of TAM biology will pave the way for the successful translation of these nano-therapies into clinical practice.

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Enhanced Therapeutic Effect of Optimized Melittin-dKLA, a Peptide Agent Targeting M2-like Tumor-Associated Macrophages in Triple-Negative Breast Cancer

Cited by 10 publications

References 70 publications

The current landscape of the antimicrobial peptide melittin and its therapeutic potential

The current landscape of the antimicrobial peptide melittin and its therapeutic potential

Bee Venom - Friend or Enemy

Tumor-associated macrophages in nanomaterial-based anti-tumor therapy: as target spots or delivery platforms

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