Targeted pH-responsive delivery of rosmarinic acid via phenylboronic acid functionalized mesoporous silica nanoparticles for liver and lung cancer therapy

Abstract

Currently, chemotherapy is one of the most practiced approaches for the treatment of cancers. However, existing chemotherapeutic drugs have poor aqueous solubility, poor selectivity, higher systematic toxicity, and poor target accumulation. In this study, we designed and synthesized a boronic acid/ester-based pH-responsive nano-valve that specifically targets the microenvironment in cancer cells. The nano-valve comprises phenylboronic acid-coated mesoporous silica nanoparticles (B-MSN) loaded with polyphenolic compound Rosmarinic acid (ROS-B-MSN). The nano-valve was further coated with lignin (LIG) to achieve our desired LIG-ROS-BMSN nano-valve for targeted chemotherapy against Hep-G2 and NCI-H460 cell lines. The structure and properties of NPs were characterized by Fourier-transformed infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM) in combination with EDX, and Dynamic light scattering (DLS). The outcomes revealed that the designed LIG-ROS-BMSN were in the nanorange (144.1 ± 0.70 nm), had negative Zeta potential (-15.7 ± 0.46 mV) and had a nearly spherical morphology. In vitro, drug release investigations showed a controlled pH-dependent release profile under mild acidic conditions that could enhance the targeted chemotherapeutic response against cancer in mild acidic environments. The obtained LIG-ROS-BMSN nano valve achieved significantly lower IC₅₀ values of (1.70 ± 0.01 μg/mL and 3.25 ± 0.14 μg/mL) against Hep-G2 and NCI-H460 cell lines as compared to ROS alone, which was (14.0 ± 0.7 μg/mL and 29.10 ± 0.25 μg/mL), respectively. The cellular morphology before and after treatment was further confirmed via inverted microscopy. The outcomes of the current study imply that our designed LIG-ROS-BMSN nanovalve is a potential carrier for cancer chemotherapeutics.

GRAPHICAL ABSTRACT

Keywords:

• Targeted chemotherapy
• rosmarinic acid
• pH-responsive drug delivery
• boronic acid silica nanoparticles
• liver cancer cells
• lung cancer cells

Acknowledgments

The authors would like to thank H.E.J Research Institute of Chemistry University of Karachi and Higher Education Commission for funding and support.

Credit authorship contribution statement

Muhammad Kawish: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, writing (original draft), review, and editing. Nimra Naz Siddiqui: In vitro cellular experiments. Abdelbari Elhissi, Humera Jahan: Methodology and manuscript review. Hina Zahid: Writing – review & editing. Bushra khatoon: Methodology. Muhammad Raza Shah: Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – review & editing.

Disclosure statement

The author(s) reported no potential conflicts of interest.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.