H-Dots: Renal Clearable Zwitterionic Nanocarriers for Disease Diagnosis and Therapy

Nanocarriers have shown significant promise in the diagnosis and treatment of various diseases, utilizing a wide range of biocompatible materials such as metals, inorganic substances, and organic components. Despite diverse design strategies, key physicochemical properties, including hydrodynamic diameter, shape, surface charge, and hydrophilicity/lipophilicity, are crucial for optimizing biodistribution, pharmacokinetics, and therapeutic efficacy. However, these properties are often influenced by drug payload, presenting an ongoing challenge in developing versatile platform technologies for theranostics. To enable tissue- and organ-specific targeting while minimizing nonspecific uptake, renal clearable Harvard dots (H-dots) have emerged as a promising organic nanocarrier platform. Composed of an ε-polylysine backbone for a tunable charge, near-infrared fluorophores for tracking their fate in living organisms, and β-cyclodextrins for potential drug delivery, H-dots offer a multifunctional approach to theranostic nanomedicine. Recent studies demonstrate that H-dots are effective for targeted imaging and drug delivery to solid tumors. This review highlights current nanocarrier design strategies and recent advances in H-dot applications for cancer diagnosis and therapy.