Nanoparticles in cancer therapy: Strategies to penetrate and modulate the tumor microenvironment – A review

Abstract

Despite advances in conventional cancer treatments such as surgery, chemotherapy, and radiation, these approaches still face significant challenges, including systemic toxicity, limited tumor specificity, and therapy resistance. These limitations highlight the need for more effective, targeted therapeutic strategies. Nanotechnology has emerged as a promising solution in oncology, offering enhanced drug delivery, improved therapeutic efficacy, and reduced side effects. Among nanotechnology-based approaches, nanoparticle-based systems have gained clinical interest due to their biocompatibility, stability, and safety. Although various studies have investigated inorganic, organic, biological, and hybrid nanoparticles, existing reviews often focus solely on individual types, lacking direct comparisons of their performance regarding tumor penetration, controlled drug release, toxicity profiles, therapy resistance, and immune evasion capabilities. This review provides a comprehensive comparative analysis of these nanoparticle systems within the context of tumor microenvironment barriers. It also discusses critical challenges in clinical translation and highlights emerging hybrid platforms that integrate the advantages of multiple nanoparticle types, offering promising strategies for advancing cancer nanotherapy.