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Charge-switchable cell-penetrating peptides for rerouting nanoparticles to glioblastoma treatment.
- Source :
-
Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2024 Sep; Vol. 241, pp. 113983. Date of Electronic Publication: 2024 May 28. - Publication Year :
- 2024
-
Abstract
- Glioblastoma (GB) is one of the most lethal types of neoplasms with unique anatomic, physiologic, and pathologic features that usually persist after exposure to standard therapeutic modalities. It is biologically aggressive, and the existence of the blood-brain barrier (BBB) limits the efficacy of standard therapies. In this work, we hypothesize the potential of surface-functionalized ultra-small nanostructured lipid carriers (usNLCs) with charge-switchable cell-penetrating peptides (CPPs) to overcome this biological barrier and improve targeted delivery to brain tumor tissues. The big question is: what is the potential of CPPs in directing nanoparticles toward brain tumor tissue? To answer this question, the usNLCs were functionalized with distinct biomolecules [five CPPs, c(RGDfK) and transferrin, Tf] through electrostatic interaction and its ability as a targeting approach to BBB (HBMEC) and glioma cells (U87 cells) evaluated in terms of physicochemical properties, cellular uptake, permeability in a 2D-BBB model, and tumor growth inhibition. Monte Carlo simulations elucidated CPP adsorption patterns. The permeability studies revealed that targeted usNLCs, especially usNLCs <superscript>Tf</superscript> and usNLCs <superscript>CPP4</superscript> , exhibited an increased permeability coefficient compared to the non-targeted usNLCs. Functionalized usNLCs evidenced enhanced uptake in BBB cells, with smaller CPPs showing higher internalization (CPP1 and CPP2). Similarly, functionalized usNLCs exhibited more significant cytotoxicity in glioma cells, with specific CPPs promoting favorable internalization. Analysis of the endocytic pathway indicated that usNLCs <superscript>CPPs</superscript> were mainly internalized by direct translocation and caveolae-mediated endocytosis. Optimal usNLCs with dual targeting capabilities to both BBB and GB cells provide a promising therapeutic strategy for GB.<br />Competing Interests: Declaration of conflict of interests The authors declare no conflicts of interest.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Brain Neoplasms drug therapy
Brain Neoplasms pathology
Brain Neoplasms metabolism
Cell Line, Tumor
Surface Properties
Cell Proliferation drug effects
Antineoplastic Agents pharmacology
Antineoplastic Agents chemistry
Particle Size
Static Electricity
Monte Carlo Method
Cell Survival drug effects
Lipids chemistry
Drug Delivery Systems
Drug Carriers chemistry
Cell-Penetrating Peptides chemistry
Cell-Penetrating Peptides pharmacology
Glioblastoma drug therapy
Glioblastoma pathology
Glioblastoma metabolism
Nanoparticles chemistry
Blood-Brain Barrier metabolism
Blood-Brain Barrier drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4367
- Volume :
- 241
- Database :
- MEDLINE
- Journal :
- Colloids and surfaces. B, Biointerfaces
- Publication Type :
- Academic Journal
- Accession number :
- 38850741
- Full Text :
- https://doi.org/10.1016/j.colsurfb.2024.113983