Cross-Linked Lipoic Acid Trisulfide Nanoparticles: Revisiting H₂S Intervention as a Stand-alone Modality for Cancer...

Area of Science:

• Biochemistry
• Nanotechnology
• Oncology

Background:

• Hydrogen sulfide (H2S) exhibits anticancer properties but faces challenges in sustained delivery.
• Current H2S-based therapies have limited persistence in tumor tissues.

Purpose of the Study:

• To develop a novel nanoparticle system for efficient and sustained intratumoral delivery of H2S.
• To evaluate the anticancer efficacy and biocompatibility of the developed H2S-releasing nanoparticles.

Main Methods:

• Synthesis of cross-linked lipoic acid trisulfide nanoparticles (cLATN) as a combined H2S donor and transporter.
• Investigation of cLATN cellular uptake via thiol-mediated pathways.
• Assessment of H2S release kinetics and duration in tumor tissues.
• Evaluation of therapeutic efficacy and biocompatibility in preclinical cancer models.

Main Results:

• cLATN demonstrated stoichiometric H2S loading and sustained release (>48 h) triggered by glutathione.
• Nanoparticles exhibited efficient tumor cell entry through thiol-mediated uptake.
• cLATN achieved an 83% tumor inhibition rate, outperforming doxorubicin in efficacy.
• Favorable biocompatibility was observed, indicating a better safety profile than doxorubicin.

Conclusions:

• cLATN represent a promising platform for sustained H2S delivery in cancer therapy.
• This approach overcomes limitations of current H2S-based treatments, positioning H2S as a potential stand-alone anticancer modality.
• The study highlights the potential of cLATN for broader clinical applications in cancer treatment.