Liquid metal nanoparticles for enhanced delivery of benzoporphyrin derivative in photodynamic cancer therapy

Photodynamic therapy (PDT) is a targeted cancer treatment offering precise tumor ablation with minimal systemic toxicity. However, its clinical application is constrained by poor solubility, rapid clearance, and inadequate tumor accumulation of photosensitizers (PS). This study presents an innovative liquid metal nanoparticle (LMNP) platform, composed of gallium-indium eutectic alloy (EGaIn), engineered to address these drug delivery challenges in PDT. Using a one-step sonication process, EGaIn nanoparticles are synthesized and functionalized with folic acid (FA) for tumor-specific targeting, beta cyclodextrin (β-CD) for enhanced drug encapsulation, and benzoporphyrin derivative (BPD) as a PS. The inclusion of β-CD significantly improves the BPD loading capacity, achieving a three-fold enhancement (52% vs. 18%) while ensuring nanoparticle stability and sustained drug release. Covalent binding of FA and β-CD to the gallium oxide surface enables effective targeting and biocompatibility. In vitro analyses demonstrate potent PDT efficacy, even with reduced cellular uptake, underscoring the platform's ability to overcome intracellular delivery barriers. This LMNP-based nanoplatform addresses critical PDT limitations, such as suboptimal drug delivery and systemic toxicity, leveraging the unique chemical and physical properties of EGaIn nanoparticles. Its multifunctional design integrates targeted delivery, controlled release, and precise therapeutic activation, representing a promising advancement in the development of effective, personalized cancer treatment strategies.