Recent advances in melittin-based nanoparticles for antitumor treatment: from mechanisms to targeted delivery strategies

Abstract

As a naturally occurring cytolytic peptide, melittin (MLT) not only exhibits a potent direct tumor cell-killing effect but also possesses various immunomodulatory functions. MLT shows minimal chances for developing resistance and has been recognized as a promising broad-spectrum antitumor drug because of this unique dual mechanism of action. However, MLT still displays obvious toxic side effects during treatment, such as nonspecific cytolytic activity, hemolytic toxicity, coagulation disorders, and allergic reactions, seriously hampering its broad clinical applications. With thorough research on antitumor mechanisms and the rapid development of nanotechnology, significant effort has been devoted to shielding against toxicity and achieving tumor-directed drug delivery to improve the therapeutic efficacy of MLT. Herein, we mainly summarize the potential antitumor mechanisms of MLT and recent progress in the targeted delivery strategies for tumor therapy, such as passive targeting, active targeting and stimulus-responsive targeting. Additionally, we also highlight the prospects and challenges of realizing the full potential of MLT in the field of tumor therapy. By exploring the antitumor molecular mechanisms and delivery strategies of MLT, this comprehensive review may inspire new ideas for tumor multimechanism synergistic therapy.

A novel recombinant adenovirus expressing apoptin and MEL genes kills hepatocellular carcinoma cells and inhibits the growth and metastasis of ectopic tumors

“…There have been attempts to alter the sequence of MEL or ne-tune the conformation of MEL [23]. Studies have also been conducted on the delivery of MEL using smart nanocarrier strategies to achieve passive or active targeting for the treatment of recurrent and refractory malignancies [24]. The tumor-homing peptide RGD recognizes global proteins present on the surface of cancer cells and speci cally targets the vascular region of tumors.…”

Melittin alcalase-hydrolysate: a novel chemically characterized multifunctional bioagent; antibacterial, anti-biofilm and anticancer

“…The cationic nature of melittin may qualify it to play a crucial role in the disruption of cancer cell membranes through electrostatic attraction between the negatively charged membrane components of cancer cells and the positive charges of the alkaline peptides ( Adler-Nissen, 1979 ). Because of its excellent immunomodulatory effects, antitumor potency, and its ability to overcome tumor drug resistance, melittin, therefore, represents a promising agent for cancer treatment ( Yu et al, 2023 ). Moreover, a previous study showed that melittin treatment induces apoptosis in human gastric cancer (SGC-7901) cells via modulating mitochondria pathways.…”

Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives

“…In addition, nanofibers play an important role in tumor therapy, especially in overcoming the problem of tumor drug resistance. 25 , 170 Tumor drug resistance refers to the phenomenon in which tumor cells become resistant to chemotherapeutic drugs and is one of the main causes of tumor treatment failure. NPs as drug carriers can deliver chemotherapeutic drugs precisely to the tumor site, improving the therapeutic effect of the drug and reducing side effects.…”

“… 18 , 19 , 20 , 21 , 22 , 23 In the field of oncology, NPs have been extensively studied as drug carriers to overcome the problem of drug resistance faced by conventional chemotherapeutic agents. 24 , 25 NPs as drug carriers have the following advantages. First, NPs can be used efficiently for drug delivery, encapsulating chemotherapeutic agents and ensuring high drug concentrations are distributed to tumor sites to improve therapeutic efficacy.…”