- Review
Intrinsically Selective Nanoplatforms for Precision Therapy and Monitoring
- Aurelie F. Brownsberger,
- Carlie Kudary and
- Prakash D. Nallathamby
- + 9 authors
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.
9 May 2026



![Principal endocytic routes determining nanoparticle intracellular fate. Clathrin-mediated endocytosis (CME) and caveolin-mediated endocytosis (CVME) represent the primary processes of receptor-mediated endocytosis (RME). Conversely, additional RME mechanisms, such as flotillin, ARF6, RhoA, or CDC42-mediated endocytosis, also exist within the cell. Adapted with permissions from [66] 2020 Manzanares et al.](https://mdpi-res.com/cdn-cgi/image/width=281%2Cheight=192/https://mdpi-res.com/jnt/jnt-07-00011/article_deploy/html/images/jnt-07-00011-ag-550.jpg)

![Adding gadolinium contrast agent makes brain tumors significantly easier to spot under MRI [18]. Nanocarrier-based gadolinium formulations, such as liposomal or fullerene-based nanoparticles, improve imaging sensitivity while reducing systemic exposure and toxicity [19,90]. In the context of personalized nanomedicine, nanoparticle-based imaging approaches can provide information on tumor localization, vascular permeability, and microenvironmental characteristics that influence nanoparticle accumulation and delivery. Such imaging strategies may therefore support disease characterization, patient stratification, and longitudinal monitoring of therapeutic responses [6,16,17,91]. Abbreviations: MRI, magnetic resonance imaging. Created in BioRender. Sharon, S. (2026) https://BioRender.com/vidamsv (accessed on 7 April 2026).](https://mdpi-res.com/cdn-cgi/image/width=281%2Cheight=192/https://mdpi-res.com/jnt/jnt-07-00009/article_deploy/html/images/jnt-07-00009-ag-550.jpg)
