Evidence That a Peptide-Drug/p53 Gene Complex Promotes Cognate Gene Expression and Inhibits the Viability of Glioblastoma Cells

Sep 21, 2026

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Glioblastoma multiform (GBM) is the deadliest brain cancer, and conventional treatments yield limited survival, driving the search for more effective therapies. The study develops temozolomide–transferrin (Tf) peptide (WRAP5)/p53 gene nanometric complexes shown to be biocompatible, enabling targeting and internalization into SNB19 and U373 glioma cells. Transfection induces p53 expression and increases anticancer cytotoxicity via apoptosis, supported by caspase-3 activation, caspase-9 elevation, and Bax overexpression. Results indicate strong potential for peptide TMZ/p53 co-delivery to promote transfection, p53 expression, and apoptosis for glioblastoma therapy.

LanguageEnglish

CategoryHealthcare

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Pages26

Reading Time1 h 6 min

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Abstract

Introduction

pharmaceutics Article Evidence That a Peptide-Drug/p53 Gene Complex Promotes Cognate Gene Expression and Inhibits the Viability of Glioblastoma Cells Ana Neves 1, T¥nia Albuquerque 1, Róben Faria 1, Cec½lia R. A. Santos 1, Eric Viv±s 2, Prisca Boisgu²rin 2, Diana Carneiro 3, Daniel F. Bruno 3, Maria D. Pavlaki 3, Susana Loureiro 3, 􀂅ngela Sousa 1 and Diana Costa 1, * Citation: Neves, A.; Albuquerque, T.; Faria, R.; Santos, C.R.A.; Viv±s, E.; Boisgu²rin, P.; Carneiro, D.; Bruno, D.F.; Pavlaki, M.D.; Loureiro, S.; et al. Evidence That a Peptide-Drug/p53 Gene Complex Promotes Cognate Gene Expression and Inhibits the Viability of Glioblastoma Cells. Pharmaceutics 2024, 16, 781 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)pharmaceutics16060781 Academic Editor: Wei Wu Received: 25 April 2024 Revised: 28 May 2024 Accepted: 4 June 2024 Published: 8 June 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 CICS-UBI—Health Sciences Research Centre, University of Beira Interior, 6201-001 Covilh¢, Portugal; [a34643@ubi.pt](a34643@ubi.pt) (A.N.); [tania.albuquerque@ubi.pt](tania.albuquerque@ubi.pt) (T.A.); [ruben.faria@ubi.pt](ruben.faria@ubi.pt) (R.F.); [csantos@fcsaude.ubi.pt](csantos@fcsaude.ubi.pt) (C.R.A.S.); [angela@fcsaude.ubi.pt](angela@fcsaude.ubi.pt) (􀂅.S.) 2 PhyMedExp, INSERM, CNRS, University of Montpellier, 34295 Montpellier, France; [eric.vives@umontpellier.fr](eric.vives@umontpellier.fr) (E.V.); [prisca.boisguerin@inserm.fr](prisca.boisguerin@inserm.fr) (P.B.) 3 CESAM—Centre for Environmental and Marine Studies, Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal; [dianaisabel@ua.pt](dianaisabel@ua.pt) (D.C.); [danielbruno@ua.pt](danielbruno@ua.pt) (D.F.B.); [maria.pavlaki@ua.pt](maria.pavlaki@ua.pt) (M.D.P.); [sloureiro@ua.pt](sloureiro@ua.pt) (S.L.) * Correspondence: [dcosta@fcsaude.ubi.pt](dcosta@fcsaude.ubi.pt) Abstract: Glioblastoma multiform (GBM) is considered the deadliest brain cancer. Conventional therapies are followed by poor patient survival outcomes, so novel and more efﬁcacious therapeutic strategies are imperative to tackle this scourge. Gene therapy has emerged as an exciting and innovative tool in cancer therapy. Its combination with chemotherapy has signiﬁcantly improved therapeutic outcomes. In line with this, our team has developed temozolomide–transferrin (Tf) peptide (WRAP5)/p53 gene nanometric complexes that were revealed to be biocompatible with non-cancerous cells and in a zebraﬁsh model and were able to efﬁciently target and internalize into SNB19 and U373 glioma cell lines. The transfection of these cells, mediated by the formulated peptide-drug/gene complexes, resulted in p53 expression. The combined action of the anticancer drug with p53 supplementation in cancer cells enhances cytotoxicity, which was correlated to apoptosis activation through quantiﬁcation of caspase-3 activity. In addition, increased caspase-9 levels revealed that the intrinsic or mitochondrial pathway of apoptosis was implicated. This assumption was further evidenced by the presence, in glioma cells, of Bax protein overexpression—a core regulator of this apoptotic pathway. Our ﬁndings demonstrated the great potential of peptide TMZ/p53 co-delivery complexes for cellular transfection, p53 expression, and apoptosis induction, holding promising therapeutic value toward glioblastoma. Keywords: apoptosis; caspases; cell-penetrating peptides; co-delivery; glioblastoma therapy; p53 1. Introduction Glioblastoma multiform (GBM) is the most common malignant adult brain cancer, characterized by a poor prognosis (approximately 15 months

FAQs

What are the key effects of the peptide-drug/p53 gene complexes on glioblastoma cells?

The complexes enhance p53 expression and increase cytotoxicity in glioma cells. They also trigger apoptosis through caspase activation and related apoptotic markers.

How does the study link apoptosis to specific caspase activities?

Apoptosis is supported by quantification of caspase-3 activity, along with increased caspase-9 levels indicating involvement of the intrinsic/mitochondrial apoptosis pathway.

Why is delivering therapies locally in glioma emphasized in the work?

The approach targets delivery directly after tumor removal by intracranial injection to reduce issues related to blood–brain barrier penetration and drug removal from circulation.

Sep 21, 2026

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