Bioengineering stimuli-responsive organic-inorganic nanoarchitetures based on carboxymethylcellulose-poly-l-lysine nanoplexes: Unlocking the potential for bioimaging and multimodal chemodynamic-magnetothermal therapy of brain cancer cells.

in International journal of biological macromolecules by Alexandra A P Mansur, Sandhra M Carvalho, Zélia I P Lobato, M Fátima Leite, Klaus Krambrock, Herman S Mansur

TLDR

  • Scientists designed novel hybrid nanoplexes for bioimaging and killing brain cancer cells, demonstrating effective production and promising results, paving the way for future research and potential clinical applications.

Abstract

Regrettably, glioblastoma multiforme (GBM) remains the deadliest form of brain cancer, where the early diagnosis plays a pivotal role in the patient's therapy and prognosis. Hence, we report for the first time the design, synthesis, and characterization of new hybrid organic-inorganic stimuli-responsive nanoplexes (NPX) for bioimaging and killing brain cancer cells (GBM, U-87). These nanoplexes were built through coupling two nanoconjugates, produced using a facile, sustainable, green aqueous colloidal process ("bottom-up"). One nanocomponent was based on cationic epsilon-poly-l-lysine polypeptide (εPL) conjugated with ZnS quantum dots (QDs) acting as chemical ligand and cell-penetrating peptide (CPP) for bioimaging of cancer cells (QD@εPL). The second nanocomponent was based on anionic carboxymethylcellulose (CMC) polysaccharide surrounding superparamagnetic magnetite "nanozymes" (MNZ) behaving as a capping macromolecular shell (MNZ@CMC) for killing cancer cells through chemodynamic therapy (CDT) and magnetohyperthermia (MHT). The results demonstrated the effective production of supramolecular aqueous colloidal nanoplexes (QD@εPL_MNZ@CMC, NPX) integrated into single nanoplatforms, mainly electrostatically stabilized by εPL/CMC biomolecules with anticancer activity against U-87 cells using 2D and 3D spheroid models. They displayed nanotheranostics (i.e., diagnosis and therapy) behavior credited to the photonic activity of QD@εPL with luminescent intracellular bioimaging, amalgamated with a dual-mode killing effect of GBM cancer cells through CDT by nanozyme-induced biocatalysis and as "nanoheaters" by magnetically-responsive hyperthermia therapy.

Overview

  • The study aimed to design, synthesize, and characterize new hybrid organic-inorganic nanoplexes (NPX) for bioimaging and killing brain cancer cells (GBM, U-87).
  • The researchers created two nanoconjugates using a green aqueous colloidal process, one based on cationic epsilon-poly-l-lysine polypeptide (εPL) conjugated with ZnS quantum dots (QDs) and the other based on anionic carboxymethylcellulose (CMC) polysaccharide surrounding superparamagnetic magnetite 'nanozymes' (MNZ).
  • The primary objective was to develop a nanotheranostic platform that could visualize and treat GBM cells using photonic activity and chemodynamic therapy (CDT) and magnetohyperthermia (MHT).

Comparative Analysis & Findings

  • The results showed the effective production of supramolecular aqueous colloidal nanoplexes (QD@εPL_MNZ@CMC, NPX) with anticancer activity against U-87 cells using 2D and 3D spheroid models.
  • The nanoplexes displayed nanotheranostics behavior, with photonic activity of QD@εPL allowing for luminescent intracellular bioimaging, and a dual-mode killing effect of GBM cancer cells through CDT and MHT.
  • TheNPX demonstrated electrostatic stabilization by εPL/CMC biomolecules, which facilitated their interactions with GBM cells and enabled targeted delivery of the nanotherapeutic agents.

Implications and Future Directions

  • The study highlights the potential of the developed NPX for diagnosis and therapy of GBM, a devastating brain cancer, and underscores the need for further research to explore its clinical applicability and overcome the challenges associated with its translation.
  • Future studies should focus on exploring the NPX's therapeutic efficacy in preclinical models and investigating its potential as a personalized treatment approach.
  • The researchers suggest that the NPX could be optimized for specific cancer types and tailored for individual patients, which would require a multidisciplinary approach incorporating engineering, biology, and clinical expertise.
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