Targeted pH-responsive delivery of rosmarinic acid <i>via</i> 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 nano range (144.1 ± 0.70 nm) had negative Zeta potential (-15.7 ± 0.46 mV) and 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 mild acidic environments of cancer. 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 implying that our designed LIG-ROS-BMSN nano valve is a potential carrier for cancer chemotherapeutics.

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