Design, Synthesis and Activity of New N1-Alkyl Tryptophan Functionalized Dendrimeric Peptides against Glioblastoma

Sowińska, Marta; Szeliga, Monika; Morawiak, Maja; Zabłocka, Barbara; Urbańczyk‐Lipkowska, Zofia

doi:10.3390/biom12081116

Cited by 11 publications

(4 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to the limited data here, the affinity, specificity, and inhibitory activity of P152 should be extensively studied by various investigations, such as co-immunoprecipitation, flow cytometry, and confocal microscopy assays, in the future. Further P152-based modification and functionalization, such as sequence optimization and structure modification, may enhance its anti-migration potency [ 30 ]. P152 suppressing cancer cell migration may reduce the metastasis ability of cancer cells [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

Screening of EWI-2-Derived Peptides for Targeting Tetraspanin CD81 and Their Effect on Cancer Cell Migration

et al. 2023

View full text Add to dashboard Cite

CD81, a transmembrane protein belonging to the tetraspanin family, has recently been suggested as a therapeutic target for cancers. Here, we screened peptides that bind to the tetraspanin CD81 protein, and evaluated their inhibitory activity in cancer cell migration. To screen for CD81-binding peptides (CD81-BP), a peptide array membrane was prepared from the amino acid sequence of the EWI-2 protein, a major partner of CD81, before binding to fluorescently labeled CD81. As a result, four candidate CD81-BPs were identified and characterized. In particular, the CFMKRLRK peptide (called P152 in this study) was found to be the best candidate that preferentially binds to the extracellular loop of CD81, with an estimated dissociation constant of 0.91 µM. Since CD81 was reported to promote cancer cell migration, an initial step in metastasis, the Boyden chamber assay, was next performed to assess the effect of CD81-BP candidates on the migration of MDA-MB-231 human breast cancer cells. Interestingly, our result indicated that P152 could suppress MDA-MB-231 cell migration at the level comparable to that of an anti-human CD81 antibody (5A6). Thus, we propose these CD81-BPs with the anti-migration property against cancer cells for the development of novel therapeutic strategies.

show abstract

Section: Resultsmentioning

confidence: 99%

Screening of EWI-2-Derived Peptides for Targeting Tetraspanin CD81 and Their Effect on Cancer Cell Migration

et al. 2023

View full text Add to dashboard Cite

show abstract

“…PAMAM, as one of the most studied dendrimers, was engineered as a carrier for the delivery of antitumor drugs to GBM [ 211 ]. Amphiphilic peptide dendrimers [ 212 ], poly(propyleneimine) [ 213 ] and Poly(L-lysine) [ 214 ] were used for the same purpose as well. Surface modifications of dendrimers were studied for effectiveness in targeting GBM [ 215 ].…”

Section: Nanocarrier Treatment Optionsmentioning

confidence: 99%

Mechanisms of Resistance and Current Treatment Options for Glioblastoma Multiforme (GBM)

Yalamarty

Filipczak

et al. 2023

Cancers

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer that is difficult to treat due to its resistance to both radiation and chemotherapy. This resistance is largely due to the unique biology of GBM cells, which can evade the effects of conventional treatments through mechanisms such as increased resistance to cell death and rapid regeneration of cancerous cells. Additionally, the blood–brain barrier makes it difficult for chemotherapy drugs to reach GBM cells, leading to reduced effectiveness. Despite these challenges, there are several treatment options available for GBM. The standard of care for newly diagnosed GBM patients involves surgical resection followed by concurrent chemoradiotherapy and adjuvant chemotherapy. Emerging treatments include immunotherapy, such as checkpoint inhibitors, and targeted therapies, such as bevacizumab, that attempt to attack specific vulnerabilities in GBM cells. Another promising approach is the use of tumor-treating fields, a type of electric field therapy that has been shown to slow the growth of GBM cells. Clinical trials are ongoing to evaluate the safety and efficacy of these and other innovative treatments for GBM, intending to improve with outcomes for patients.

show abstract

“…Dendrimers are the hyperbranched, multifunctional, and nanosized macromolecules having a core and repetitive external branching units. 11 The branching and multiple functional surfaces of dendrimers bring forth massive sites for ligands and drugs for conjugation. This makes dendrimers a tailor-made nano drug carrier.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, dendrimers have emerged as promising chemotherapeutic delivery tools among many nano drug delivery carriers. Dendrimers are the hyperbranched, multifunctional, and nanosized macromolecules having a core and repetitive external branching units . The branching and multiple functional surfaces of dendrimers bring forth massive sites for ligands and drugs for conjugation.…”

Section: Introductionmentioning

confidence: 99%

Angiopep-2 Grafted PAMAM Dendrimers for the Targeted Delivery of Temozolomide: In Vitro and In Vivo Effects of PEGylation in the Management of Glioblastoma Multiforme

Sahoo

Kumar

Jain

et al. 2023

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

The present study was aimed to synthesize, characterize, and evaluate the angiopep-2 grafted PAMAM dendrimers (Den, G 3.0 NH2) with and without PEGylation for the targeted and better delivery approach of temozolomide (TMZ) for the management of glioblastoma multiforme (GBM). Den-ANG and Den-PEG2-ANG conjugates were synthesized and characterized by 1H NMR spectroscopy. The PEGylated (TMZ@Den-PEG2-ANG) and non-PEGylated (TMZ@Den-ANG) drug loaded formulations were prepared and characterized for particle size, zeta potential, entrapment efficiency, and drug loading. An in vitro release study at physiological (pH 7.4) and acidic pH (pH 5.0) was performed. Preliminary toxicity studies were performed through hemolytic assay in human RBCs. MTT assay, cell uptake, and cell cycle analysis were performed to evaluate the in vitro efficacy against GBM cell lines (U87MG). Finally, the formulations were evaluated in vivo in a Sprague–Dawley rat model for pharmacokinetics and organ distribution analysis. The 1H NMR spectra confirmed the conjugation of angiopep-2 to both PAMAM and PEGylated PAMAM dendrimers, as the characteristic chemical shifts were observed in the range of 2.1 to 3.9 ppm. AFM results revealed that the surface of Den-ANG and Den-PEG2-ANG conjugates were rough. The particle size and zeta potential of TMZ@Den-ANG were observed to be 229.0 ± 17.8 nm and 9.06 ± 0.4 mV, respectively, whereas the same for TMZ@Den-PEG2-ANG were found to be 249.6 ± 12.9 nm and 10.9 ± 0.6 mV, respectively. The entrapment efficiency of TMZ@Den-ANG and TMZ@Den-PEG2-ANG were calculated to be 63.27 ± 5.1% and 71.48 ± 4.3%, respectively. Moreover, TMZ@Den-PEG2-ANG showed a better drug release profile with a controlled and sustained pattern at PBS pH 5.0 than at pH 7.4. The ex vivo hemolytic study revealed that TMZ@Den-PEG2-ANG was biocompatible in nature as it showed 2.78 ± 0.1% hemolysis compared to 4.12 ± 0.2% hemolysis displayed by TMZ@Den-ANG. The outcomes of the MTT assay inferred that TMZ@Den-PEG2-ANG possessed maximum cytotoxic effects against U87MG cells with IC50 values of 106.62 ± 11.43 μM (24 h) and 85.90 ± 9.12 μM (48 h). In the case of TMZ@Den-PEG2-ANG, the IC50 values were reduced by 2.23-fold (24 h) and 1.36-fold (48 h) in comparison to pure TMZ. The cytotoxicity findings were further confirmed by significantly higher cellular uptake of TMZ@Den-PEG2-ANG. Cell cycle analysis of the formulations suggested that the PEGylated formulation halts the cell cycle at G2/M phase with S-phase inhibition. In the in vivo studies, the half-life (t 1/2) values of TMZ@Den-ANG and TMZ@Den-PEG2-ANG were enhanced by 2.22 and 2.76 times, respectively, than the pure TMZ. After 4 h of administration, the brain uptake values of TMZ@Den-ANG and TMZ@Den-PEG2-ANG were found to be 2.55 and 3.35 times, respectively, higher than that of pure TMZ. The outcomes of various in vitro and ex vivo experiments promoted the use of PEGylated nanocarriers for the management of GBM. Angiopep-2 grafted PEGylated PAMAM dendrimers can be potential and promising drug carri...

show abstract

Design, Synthesis and Activity of New N1-Alkyl Tryptophan Functionalized Dendrimeric Peptides against Glioblastoma

Cited by 11 publications

References 75 publications

Screening of EWI-2-Derived Peptides for Targeting Tetraspanin CD81 and Their Effect on Cancer Cell Migration

Screening of EWI-2-Derived Peptides for Targeting Tetraspanin CD81 and Their Effect on Cancer Cell Migration

Mechanisms of Resistance and Current Treatment Options for Glioblastoma Multiforme (GBM)

Angiopep-2 Grafted PAMAM Dendrimers for the Targeted Delivery of Temozolomide: In Vitro and In Vivo Effects of PEGylation in the Management of Glioblastoma Multiforme

Contact Info

Product

Resources

About