CBPUV nanoparticles show excellent anticancer activity

Scientists from the Japan Advanced Institute of Science and Technology (JAIST) and the Centre National de la Recherche Scientifique (CNRS) have created new self-assembled amino acid based nanoparticles that showed excellent anticancer efficacy. These nanoparticles could help to fight multi-drug resistance in cancer and improve the overall efficacy of treatment outcomes.

Amino acids, the fundamental molecules that form proteins, have different chemical groups on each end and side chain, and therefore can form a chain by forming an amide bond. However, these linkages are weak and easily degraded under physiological conditions.

In the new study, the team was led by Dr Eijiro Miyako, Associate Professor at the Japan Advanced Institute of Science and Technology (JAIST), and Dr Alberto Bianco and Dr Cécilia Ménard-Moyon from the Centre National de la Recherche Scientifique (CNRS). To crosslink the Fmoc-protected amino acids, they employed ultraviolet light at 254 nm, which led to CBPUV nanoparticles, and riboflavin-mediated crosslinking at 365 nm led to CBPRibo nanoparticles.

Dr Miyako said: “Amino acids being the building blocks of proteins have numerous advantages, such as better biocompatibility. Therefore, we wanted to create novel self-assembled amino acid-based nanoparticles which can be triggered through multiple mechanisms.”

The self-assembled amino acids were stably crosslinked dimers of Fmoc-Tyr-OH (Tyrosine) and Fmoc-Trp-OH (Tryptophan). Then, the anticancer drug doxorubicin was loaded into the crosslinked amino acid nanoparticles. The researchers used a tannic acid-Iron (Fe³⁺) complex (or TAF) as the outer layer of coating to increase the stability of the nanoparticles. This coating can degrade inside the cells through the glutathione enzymatic release or by pH difference in the tumour microenvironment.

Also, the coating can be used in photothermal anticancer therapy, where external light increases the temperature surrounding the cancer tissue, causing cancer cell death.

A combined approach

The synthesised nanoparticles were studied for their structural integrity, stability, and drug release under different pH conditions. Using cell culture techniques, the functional profile, cellular uptake, and biocompatibility of self-assembled amino acid nanoparticles were then studied.

After crosslinking, the amino acid-based nanoparticles showed changes in colour, size, absorbance, fluorescence, and thermal stability. Compared to CBPRibo, CBPUV showed superior stability after crosslinking. CBPUV also consistently maintained its structure, but CBPRibo exhibited partial disassembly, forming hollow spheres.

A stable coating is essential for in vivo delivery. Minimal drug release under physiological pH 7.4 was shown.  At pH 5.5, incomplete coating degradation resulted in negligible drug release. However, the addition of glutathione (GSH) at pH 5.5 significantly boosted drug release by initiating TAF coating degradation, indicating GSH/pH responsiveness.

The combined acidic and GSH treatment intensified coating degradation: this responsive behaviour enables controlled drug release in specific physiological conditions. In vitro assessments demonstrated concentration-dependent cytotoxicity and improved efficacy in combined chemo/photothermal therapy. Finally, in vivo studies on tumour-bearing mice showed much tumour growth inhibition, which promises anticancer effects without observed side effects.

Dr Miyako concluded: “Nanotechnology holds promise of transforming basic laboratory science into a powerful tool for combating complex diseases like cancer. We are optimistic that this pioneering research will advance, potentially evolving into cutting-edge cancer treatment technology ready for clinical trials within ten years.”

The study was published in Small.