Nanocapsules with remote control to locally amplify the effect of chemotherapy

by Virginia Greco

A research published in ACS Nano and featured on the cover of the issue proposes externally controlled iron magnetoplasmonic nanocapsules for cancer treatment. Satisfactory results have already been obtained in the preclinical phase in mice. This study was carried out by reseachers from the Barcelona Institute of Microelectronics (IMB-CNM-CSIC), the Catalan Institute of Nanoscience and Nanotechnology (ICN2) and the Hebrew University of Jerusalem (HU).

An international team of researcher has developed biodegradable magnetoplasmonic nanocapsules based on metallic iron and loaded with a chemotherapy drug, which are externally controlled with magnetic fields and light, to eradicate tumors using only an ultra-low concentration of the drug. These are the first results published in the journal ACS Nano of a joint research between the Institute of Microelectronics of Barcelona (IMB-CNM-CSIC), the Catalan Institute of Nanoscience and Nanotechnology (ICN2) and the Hebrew University of Jerusalem (HU). The work has been featured on one of the covers of this month's issue of the journal.

The nanocapsules can locally amplify the therapeutic action of the drugs owing to the magnetic increase of their concentration in the tumor and the amplification of the therapeutic effect induced by the local heat generated by the nanocapsules, when they absorb infrared light from an external laser. In this way, side effects are also minimized and unnecessary damage to healthy tissue is avoided.

In vivo therapeutic trials have been carried out in mice on models of human breast tumors and the results have been satisfactory, eliminating tumors with the intravenous administration of the encapsulated drug in nanometric dimensions, at a concentration between 200 and 500 times lower than its therapeutic window.

"By depositing a thin layer of metallic iron on drug-loaded nanocapsules, we have managed to integrate very robust nanomagnets, but colloidally stable thanks to their special magnetic configuration, which minimizes the interaction between them and prevents their aggregation," explains Borja Sepúlveda, principal investigator of the project, now at the IMB-CNM and previously at the ICN2 in the Magnetic Nanostructures Group. The others ICN2 researchers involved in this work are Aritz Lafuente (Doctoral Student), Dr Zhi Li (former Doctoral Student at the ICN2), Dr María José Esplandiu Egido (CSIC Scientific Researcher), Dr Alejandro Gómez Roca (Senior Researcher), ICREA Prof. Josep Nogués Sanmiquel (group leader).

The metallic iron nanolayer "allows us to take advantage of its plasmonic behavior to absorb near-infrared light, which has a high penetration into tissues, very efficiently to generate local heat," he adds. This combination allows "magnetically increasing the concentration of nanocapsules in the tumor and amplifying the therapeutic effect of the encapsulated drug through local hyperthermia induced with an external laser." After the external actuation, the nanocapsules degrade quickly and thus avoid problems of bioaccumulation and toxicity.

Promising results for application in tumors and other diseases

The study has shown that, by improving the administration and efficacy of therapeutic agents through nanocapsules, the concentration of injected drug can be drastically reduced, which could reduce the treatment period, in addition to reduce the frequency and doses of chemotherapy. Another advantage derived from the magnetism of nanocapsules is that it allows non-invasive visualization of their biodistribution and accumulation in the tumor by magnetic resonance. The promising therapeutic results of magnetoplasmonic nanocapsules provide glimpses of applications that could easily spread to other drugs and tumors, and even to other diseases.

The next step of the research is to demonstrate that the strategy is effective with other chemotherapy or photodynamic drugs and for other types of tumors. At the same time, in the MAPSCALE project (MCIN/AEI /10.13039/501100011033 and EU Next Generation EU/ PRTR, 01-12-2022 / 30-11-2024, IP: Josep Nogués / Borja Sepúlveda) a prototype is also being developed to scale up the production of the semi-metal-coated nanocapsules.

Reference article:

Arnon Fluksman, Aritz Lafuente, Zhi Li, Jordi Sort, Silvia Lope-Piedrafita, Maria José Esplandiu, Josep Nogues, Alejandro G. Roca, Ofra Benny, and Borja Sepulveda, Efficient Tumor Eradication at Ultralow Drug Concentration via Externally Controlled and Boosted Metallic Iron Magnetoplasmonic Nanocapsules. ACS Nano 2023, 17, 3, 1946–1958. DOI: 10.1021/acsnano.2c05733