Tumor microenvironment-responsive degradable silica nanoparticles: design principles and precision theranostic applications

Silica nanoparticles have emerged as promising candidates in the field of nanomedicine due to their remarkable versatility and customizable properties. However, concerns about their potential toxicity in healthy tissues and organs have hindered their widespread clinical translation. To address this challenge, significant attention has been directed toward a specific subset of silica nanoparticles, namely degradable silica nanoparticles, primarily because of their excellent biocompatibility and responsive biodegradability. In this review, we provide a comprehensive understanding of degradable silica nanoparticles, categorizing them into two distinct groups: inorganic species-doped and organic moiety-doped silica nanoparticles based on their framework components. Next, the recent progress of tumor microenvironment (TME)-responsive degradable silica nanoparticles for precision theranostic applications is summarized in detail. Finally, current bottlenecks and future opportunities of theranostic nanomedicines based on degradable silica nanoparticles in clinical applications are also outlined and discussed. The aim of this comprehensive review is to shed light on the potential of degradable silica nanoparticles in addressing current challenges in nanomedicine, offering insights into their design, applications in tumor diagnosis and treatment, and paving the way for future advancements in clinical theranostic nanomedicines. In this review, we categorize degradable silica nanoparticles into inorganic and organic types based on their framework components, highlight recent TME-responsive advancements, and discuss challenges in future research and clinical application.