Augumenting the anticancer properties of l-phenylalanine functionalized nanoscopic porous amino acid mimics (Nano-pPAAMs)

Abstract

Therapeutic efficiencies of novel cancer treatment modalities such as photodynamic therapy (PDT) and chemodynamic therapy (CDT) are largely diminished in clinical situations due to the disease’s constantly evolving nature and harsh conditions of the tumour microenvironment (TME); such as insufficiently low intertumoural pH (pH: < 5) and hydrogen peroxide (H2O2) levels. The development of reactive oxygen species (ROS) generating nanomedicine relieves the aforementioned pain points by elevating intertumoural H2O2 levels, typically either via external stimulation (e.g., infrared radiation or ultrasound) or from the innate TME. Their ability to elevate intertumoural H2O2 levels allows them to function as either a standalone anticancer nanomedicine or an adjuvant for follow-up PDT/CDT treatments. L-phenylalanine functionalized nanoscopic porous amino acid mimics (Nano-pPAAMs) stands out amongst the emerging plethora of ROS-generating nanomaterials for their cancer selectivity and intrinsic ability to generate ROS without external stimulation. However, significant high dosages of Nano-pPAAM are required to effectively eradicate the tumour in both in vitro and in vivo studies.

In this study, to reduce the Nano-pPAAM dosage required to eradicate malignancies, two cytotoxins, cetyltrimethylammonium bromide (CTAB) and hydrogen peroxide (H2O2), were successfully loaded into the mesoporous silica nanoparticle cores. The improved Nano-pPAAMs were characterized for their particle stability, size, loading content, chemical integrity and were shown to have successfully been able to retain their cytotoxic payload. A total of six cell lines, three cancerous and three healthy cell lines were selected to evaluate the cancer selectiveness and anticancer potency of the loaded Nano-pPAAM. Based on the dose-response curves plotted, the nanoparticles in order of potency, are: Nano-pPAAM (least potent) < H2O2@pPAAM < CTAB@pPAAM (most potent). Despite the promising results obtained, additional improvements in the Nano-pPAAM design are still recommended to be performed to ensure that the improved Nano-pPAAMs are still selective towards cancer cells.