Melittin-Based Nano-Delivery Systems for Cancer Therapy

Wang, Anqi; Zhu, Wanxin; Yang, Liuxin; Yang, Yang; Peng, Jinliang

doi:10.3390/biom12010118

Cited by 38 publications

(29 citation statements)

References 146 publications

(156 reference statements)

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“…Importantly, the hemolysis effect of FMPI was dramatically decreased with its increasing concentrations compared to that of MPI (Figure 2G). Compared to traditional strategies (e.g., incorporating NPs with carriers and modifying drugs with functional ligands), [ 18 ] present results demonstrate the benefits of the fluorinated prodrug strategy in terms of reducing potential side effects of DOX and MPI.…”

Section: Resultsmentioning

confidence: 70%

Manipulating Offense and Defense Signaling to Fight Cold Tumors with Carrier‐Free Nanoassembly of Fluorinated Prodrug and siRNA

Zhang

Sun

et al. 2022

Advanced Materials

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Chemoimmunotherapy has shown great potential to activate an immune response, but the immunosuppressive microenvironment associated with T cell exhaustion remains a challenge in cancer therapy. The proper immune‐modulatory strategy to provoke a robust immune response is to simultaneously regulate T‐cell exhaustion and infiltration. Here, a new kind of carrier‐free nanoparticle is developed to simultaneously deliver chemotherapeutic drug (doxorubicin, DOX), cytolytic peptide (melittin, MPI), and anti‐TOX small interfering RNA (thymocyte selection‐associated high mobility group box protein, TOX) using a fluorinated prodrug strategy. In this way, the enhanced immunogenic cell death (ICD) induced by the combination of DOX and MPI can act as “offense” signaling to increase CD8+ T‐cell infiltration, while the decreased TOX expression interfered with siTOX can serve as “defense” signaling to mitigate CD8+ T‐cell exhaustion. As a result, the integration of DOX, MPI, and siTOX in such a bifunctional system produced a potent antitumor immune response in liver cancer and metastasis, making it a promising delivery platform and effective strategy for converting “cold” tumors into “hot” ones.

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Section: Resultsmentioning

confidence: 70%

Manipulating Offense and Defense Signaling to Fight Cold Tumors with Carrier‐Free Nanoassembly of Fluorinated Prodrug and siRNA

Zhang

Sun

et al. 2022

Advanced Materials

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“…RLX has shown efficacy against pancreatic adenocarcinoma growth through ERβ and the IL-6/gp130/STAT3 signaling pathway interference in PDAC cell line (Pozios et al, 2021 ). MEL has been widely investigated for utilization in cancer therapy, for reviews (Liu et al, 2016 ; Wang et al, 2022 ). MEL has demonstrated effectiveness in enhancing apoptosis through the enhancement of death receptor 3 expression and inhibition of NF-κB pathway in A549 and NCI-H460 cells and downregulating of ERK and Akt signaling pathway in leukemic U937 cells (Moon et al, 2006 ; Choi et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“…This peptide has shown promise in wound healing, oxidative stress, apoptosis, inflammation, antiviral, and multi-resistant bacterial infection (Moreno & Giralt, 2015 ; Mahmoudi et al, 2020 ; Memariani et al, 2020 ; Lima et al, 2021 ; Eid et al, 2022 ). Various reports have indicated promising anticancer activity of MEL (Gajski & Garaj-Vrhovac, 2013 ; Liu et al, 2016 ; Rady et al, 2017 ; Wang et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Potentiality of raloxifene loaded melittin functionalized lipidic nanovesicles against pancreatic cancer cells

et al. 2022

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Pancreatic cancer (PC) frequency and incidence have grown rapidly in recent years. One of the most serious problems with PC is the existence of asymptotic manifestations, which frequently delays early detection, and until the diagnosis is established, tumor cells progress to the metastatic stage. Another significant concern with PC is the scarcity of well-defined pharmacotherapeutic drugs. The aim of this study was to develop an efficient nanocarrier system to augment the efficacy of raloxifene (RLX) against PC cells. As a result, the current investigation was carried out in order to give an effective treatment method, in which an optimum RLX loaded phospholipid-based vesicles with melittin (PL-MEL) was chosen using experimental design software, with particle size, zeta potential and entrapment efficiency % as dependent variables. Furthermore, anticancer activity against PANC1 cells was assessed. The optimized nanovesicle parameters were 172.5 nm for the measured size, zeta potential of –0.69 mV, and entrapment efficiency of 76.91% that were in good agreement with the expected ones. RLX-raw, plain formula, and optimized RLX-PL-MEL showed IC 50 concentrations of 26.07 ± 0.98, 9.166 ± 0.34, and 1.24 ± 0.05 µg/mL, respectively. Furthermore, cell cycle analysis revealed that the nanovesicle was most effective in the G2-M phase, whereas Bax, and Bcl-2 estimates revealed that optimized RLX formula had the highest apoptotic activity among treatments investigated. However, as compared to RLX alone or plain formula alone, the optimized formula demonstrated higher expression of TNFα and Bax while a significant reduction of Bcl-2 and NF-κB expression was observed. mitochondrial membrane potential (MMP) analysis confirmed the apoptosis as well as the anticancer effect of the optimized formula. Thus, the present study results showed an improvement in the anti-PC effects of the RLX with phospholipid conjugated melittin, making it a novel treatment approach against PC.

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“…52,54,[91][92][93][94] Melittin is a cationic bee venom-derived 26-amino acid peptide with high lytic activity both at neutral and endosomal pH; its activity can be synthetically modulated by including an N-terminal or C-terminal cysteine for conjugation. [95][96][97] Peptide GE11 has been used in numerous applications 63,[98][99][100][101][102][103][104][105] as ligand for active targeting to the EGFR overexpressed on the surface of many cancer types. Furthermore, charge reversal by reversible acylation of melittin with dimethylmaleic anhydride (DMMAn) had been previously applied to abolish its lytic activity in the extracellular environment, albeit the endosomal escape activity was recovered upon endosomal acidification.…”

Section: Aim Of This Thesismentioning

confidence: 99%

Receptor-Targeted Dual pH-Triggered Intracellular Protein Transfer

Lyu

Yazdi

Lin

et al. 2022

ACS Biomater. Sci. Eng.

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Protein therapeutics, including monoclonal antibodies, cytokines, transcription factors, enzymes, and peptides, play an essential role against cancer, infectious diseases, cardiovascular disorders, immunological diseases, and metabolic disorders, resulting in brilliant successes. [9][10][11] Compared with chemotherapy, the critical function of protein therapeutics in treating diseases that lack effective therapeutic options relies on the unique advantages of (i) abundant species; (ii) complex set of biological functions; (iii) high specificity; (iv) fewer adverse effects; (v) excellent biocompatibility and biodegradability; and (vi) inherent amino, carboxyl, and hydroxyl groups for chemical conjugations. 12 Proteins, in contrast to genetic drugs, act on their targets in a way that is both more direct and more specific. This allows them to regulate biological processes in a way that eliminates the risk of permanent gene mutation, off-target effects brought on by persistent gene expression, and the possibility of cancer development. 11 Major challenges of protein therapeuticsThe progress path toward clinical application of proteins is neither straightforward nor uncomplicated, for example, due to the limited administration routes, low bioavailability of proteins in circulation, and host immune responses that may result in the inactivation of proteins before reaching their sites of action. 13 Therefore, biotechnologists have employed tremendous efforts to overcome the delivery drawbacks 2, 14, 15 to protect them from denaturation and degradation, facilitate tumor-targeted delivery, and control the protein release/activity in targeted sites. 16,17 Most protein medicines now available on the market were created based on extracellular targets. These extracellular targets include cell membrane proteins (PD1, HER2, CD20, etc.) and secretory proteins (TNFα, IL12, VEGF, etc.). 11,18 Despite the success of current protein products that mostly address extracellular targets, efficient cytosolic delivery of Ju, E. et al. 36 first reported that gold nanoclusters (AuNCs) can self-assemble with Streptococcus pyogenes Cas9 (SpCas9) protein under physiological conditions, and the complexes (SpCas9-AuNCs) efficiently deliver SpCas9 protein into the cell nucleus.SpCas9-AuNCs could be disassembled at a lower pH 4.5 but are stable at a higher pH 7.4. SpCas9 is delivered into cells and the cell nucleus, where it performs its cleavage function, through the assembly disassembly process. Furthermore, the E6 oncogene was effectively knockout by self-assembled SpCas9-AuNCs nanoparticles after the HPV18 E6 sgRNA transfected into cervical cancer cells. Consequently, this causes the tumorsuppressing protein p53 to resume its normal activity and induces apoptosis in cervical cancer cells but had little effect on the normal cells. Because of their unique characteristics, SpCas9-AuNCs are an intriguing biomaterial for the treatment of cancer.Nanogels are water-rich nanoscale three-dimensional polymer networks. Because of this, it is simple for nan...

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Melittin-Based Nano-Delivery Systems for Cancer Therapy

Cited by 38 publications

References 146 publications

Manipulating Offense and Defense Signaling to Fight Cold Tumors with Carrier‐Free Nanoassembly of Fluorinated Prodrug and siRNA

Manipulating Offense and Defense Signaling to Fight Cold Tumors with Carrier‐Free Nanoassembly of Fluorinated Prodrug and siRNA

Potentiality of raloxifene loaded melittin functionalized lipidic nanovesicles against pancreatic cancer cells

Receptor-Targeted Dual pH-Triggered Intracellular Protein Transfer

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