Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma

(A) PrestoBlue assay results after seeding Saos-2 cells (left) and U2OS cells (right) with different concentrations of CQD_7LD and CQD-7LDD nanoparticles and (B) TEM images of Saos-2 (i) and (ii) and U2OS (iii) and (iv) cells treated with a concentration of 10 μg/ml CQD_7LDD.

The article “Layer-by-layer assembly of nanotheranostic particles for simultaneous delivery of docetaxel and doxorubicin to target osteosarcoma” is now published in the journal APL Bioengineering.

The paper, co-authored by Liam Desmond, Simone Margini, Emilio Barchiesi, Giuseppe Pontrelli, Anh N. Phan, and Piergiorgio Gentile, reports the results of the study of a nanotheranostic delivery system (promising emerging field of medicine that combines “therapeutics” and “diagnostics”, characterized by the combination of diagnostics, treatment, and drug monitoring) of drugs against osteosarcoma (OS), a rare form of primary bone cancer that affects about 3.4 × 10⁶ individuals worldwide each year, mainly children.

Given the limitations of existing cancer therapies, the emergence of nanotheranostic platforms has generated considerable research interest in recent decades, as such platforms seamlessly integrate the therapeutic potential of pharmaceutical compounds with the diagnostic capabilities of imaging probes within a single construct.

Specifically, the study involved the development of a nanotheranostic system employing the layer-by-layer (LbL) technique on a core containing doxorubicin (DOXO) and in-house synthesized carbon quantum dots. Using chitosan and chondroitin sulfate as polyelectrolytes, a multilayer coating was constructed to encapsulate DOXO and docetaxel, achieving coordinated co-administration of both drugs. The functionalized LbL nanoparticles showed an approximate size of 150 nm, manifesting a predominantly uniform and spherical morphology, with an encapsulation efficiency of 48% for both drugs.

The presence of seven layers in these systems facilitated controlled drug release over time, as evidenced by in vitro release assays, managing to bypass some of the undesirable biological effects that can occur when the diagnostic and therapeutic phases are separated.

Finally, the impact of functionalized LbL nanoparticles was evaluated on U2OS and Saos-2 osteosarcoma cells. The synergistic effect of the two drugs proved to be crucial in inducing cell death, particularly in Saos-2 cells treated with nanoparticles at concentrations above 10 μg/ml.

Transmission electron microscopy analysis confirmed the internalization of nanoparticles into both cell types through endocytic mechanisms, revealing an underlying mechanism of necrosis-induced cell death.