Versatile Drug Delivery Platforms: The Emerging Role of Hybrid Nanoparticles in Solid Tumor Therapy

Lipid-Polymer Hybrid Nanoparticles (LPHNPs) have emerged as a revolutionary drug delivery platform in oncology, addressing critical challenges such as poor drug bioavailability, nonspecific distribution, and systemic toxicity. These hybrid systems combine the complementary advantages of polymeric nanoparticles and liposomes, offering improved biocompatibility, high drugloading capacity, and precise tumor targeting. Their unique structural composition facilitates controlled drug release and enhanced stability, enabling sustained therapeutic effects. This review focuses on the characteristics, synthesis methods, and tumor-targeting mechanisms of LPHNPs, highlighting their pivotal role in advancing solid tumor drug delivery. Various preparation techniques, including traditional two-step, modified two-step, and single-step approaches, are discussed to elucidate their contributions to nanoparticle formulation and optimization. LPHNPs employ both passive and active targeting strategies, capitalizing on tumor microenvironment-specific factors, such as pH, enzymes, and temperature, for passive targeting, and leveraging specific ligands, such as folate, antibodies, and aptamers, for active targeting. These mechanisms enhance therapeutic precision and minimize off-target effects, significantly improving treatment outcomes. With advancements in emerging nanotechnologies, LPHNPs demonstrate immense potential as next-generation drug delivery systems, providing solutions to longstanding challenges in cancer therapy. They offer a promising path toward more effective, safe, and patient-specific treatments for solid tumors. This review provides a comprehensive overview of LPHNPs, highlighting their current applications and future prospects for transforming cancer therapeutics.