Boron phenyl alanine targeted chitosan–PNIPAAm core–shell thermo-responsive nanoparticles: boosting drug delivery to glioblastoma in BNCT

Abstract

Boron neutron capture therapy (BNCT) is one of the best treatment modalities for glioblastoma multiform that could selectively kill the tumor cells. To be successful in BNCT, it is crucial to have enough ¹⁰B in the tumor. l-boron phenylalanine (l-BPA) targeted thermo-responsive core–shell nanoparticles (NPs) of chitosan-poly(N-isopropylacrylamide) (PNIPAAm) were our idea for endocytosis via sialic acid receptors, and selective delivery of ¹⁰B to glial cells. Methotrexate (MTX) was chosen as a model drug for evaluating the efficacy of NPs in tumor cells, and BPA was selected for BNCT purposes. The polymeric conjugates were synthesized and the chemical structures were approved by spectroscopic methods (FTIR, ¹H NMR, and ¹¹B NMR). Cargos were loaded efficiently (>95%) in the prepared NPs, and the release profile of MTX and BPA was studied around the lower critical solution temperature (LCST; about 39 °C). The loaded drugs were released quantitatively at the LCST, while almost no drug was released at 37 °C. The prepared NPs did not show considerable hemolysis ratio (<2%) and were still safe when loaded BPA, on U87MG cells. The MTX loaded NPs showed lower IC₅₀ (30.78 µg/mL) than the free MTX (37.03 µg/mL) in MTT assay, and targeted NPs had the lowest IC₅₀s in U87MG cell lines (27.35 µg/mL). Targeted BPA@CSSU-PNI NPs were uptaken better than the non-targeted ones by U87MG cells, and CR-39 assay showed the boron content efficiency for further applications in BNCT. This study's results introduce novel targeted thermo-responsive NPs for treating glioblastoma using BNCT.

Graphical Abstract

Keywords:

• Boron neutron capture therapy (BNCT)
• chitosan nanoparticles (Cs NPs)
• thermo-responsive NPs
• 4-boron-l-phenylalanine (l-BPA)
• glioblastoma multiform (GBM)
• targeted drug delivery

Acknowledgements

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Disclosure statement

The authors report no conflicts of interest.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials.

Additional information

Funding

The authors wish to thank the Research vice Chancellery of Isfahan University of Medical Sciences for supporting this work.