Intrinsically Selective Nanoplatforms for Precision Therapy and Monitoring

Nanoparticles offer a versatile platform for the selective eradication of pathogenic or diseased cells by integrating therapeutic payload delivery with precision targeting. Precision targeting can be achieved (1) actively through ligand conjugation, (2) passively by exploiting the physiological abnormalities of diseased tissues, or (3) intrinsically through the innate biophysical properties of the nanoparticle. Intrinsically selective nanoplatforms (iNPs) are particularly advantageous when the disease-promoting agent does not possess distinct surface markers, such as in the case of certain “untargetable cancers” or cancers without known targets. Indeed, nanocarriers for chemotherapeutic or gene delivery have achieved selective cancer cell apoptosis without requiring marker presentation, thereby expanding the therapeutic window of the payload. Disease-promoting agents whose physical properties are different from those of healthy cells are also good candidates for intrinsic nanoparticle targeting. For example, antimicrobial nanomaterials have been designed to disrupt bacterial membranes and reduce the risk of antimicrobial resistance by leveraging stiffness differentials between bacterial cell walls and eukaryotic membranes. Nanoparticle systems with intrinsic targeting mechanisms can also enable non-invasive imaging with near-infrared fluorescence, MRI, and photoacoustic imaging for real-time biodistribution tracking and treatment monitoring. This review synthesizes current innovations in nanoplatform design with intrinsic targeting capabilities, spans applications in infectious and non-communicable diseases, and discusses emerging strategies to enhance specificity, overcome resistance, and translate these platforms toward clinical and field deployment.