Schematic illustration of the controllable synthesis of LNNPs by employing nanomicelles as a template and the TME-responsive drug delivery strategy [IMGAE: PROFESSOR CHEN’S GROUP]

Nanomaterials have received considerable attention as therapeutic nanoagents in biomedical fields. Currently, the applications of conventional inorganic-organic hybrid nanoagents are severely hampered by their uncontrollable synthesis, poor tumor responsiveness, and inefficient body clearance. It remains a challenge to develop intelligent nanoagents capable of overcoming the dilemma between efficient therapy and long-term toxicity.

In a study published in Angew. Chem. Int. Ed., a research group led by Professor Chen Xueyuan from the Fujian Institute of Research on the Structure of Matter (FJIRSM) of the Chinese Academy of Sciences developed a novel class of tumor-microenvironment (TME)-responsive biodegradable nanoagents based on self-assembled lanthanide nucleotide nanoparticles (LNNPs).

The researchers constructed amorphous LNNPs of finely tunable size (4.6-105.7 nm) and highly uniform monodispersity by employing nanomicelles as a template.

Taking advantage of the porous network structure and TME-responsive biodegradable feature of LNNPs, the researchers realized highly efficient loading of drugs like doxorubicin (DOX) and stimuli-responsive drug release with the activation of H2O2 and acidic pH in tumor cells.

They observed the unique accumulation of ultrasmall DOX@LNNPs (sub-5 nm) in tumors with the peak level of 9.42 percent ID/g at 12 h p.i., indicating their superior tumor targeting efficiency. Meanwhile, the blood circulation half-life of ultrasmall DOX@LNNPs was determined to be 3.3 h, which is superior to that of traditional renal-clearable nanomaterials (t1/2< 2 h). The proposed nanoagents can be excreted from the body within 24 h via renal pathway, which fundamentally reduces long-term toxicity in vivo. Benefiting from high tumor accumulation, TME-responsive drug release, and rapid renal clearance of the nanoagents, the researchers realized significantly improved chemotherapy efficacy upon targeted tumor sites without evident systemic toxicity.

This study provides a novel approach to constructing inorganic-organic hybrid nanoagents for nontoxic and precise cancer therapy, and may thereby accelerate the exploitation and clinical translation of lanthanide-containing nanomedicine for further biomedical applications.

For more information, please contact:

Professor Chen Xueyuan

E-mail: xchen@fjirsm.ac.cn

Fujian Institute of Research on the Structure of Matter (FJIRSM),

Chinese Academy of Sciences

Source: Fujian Institute of Research on the Structure of Matter (FJIRSM),

Chinese Academy of Sciences