Going even smaller: Engineering sub‐5 nm nanoparticles for improved delivery, biocompatibility, and functionality

Abstract

The rapid development and advances in nanomaterials and nanotechnology in the past two decades have made profound impact in our approaches to individualized disease diagnosis and treatment. Nanomaterials, mostly in the range of 10-200 nm, developed for biomedical applications provide a wide range of platforms for building and engineering functionalized structures, devices, or systems to fulfill the specific diagnostic and therapeutic needs. Driven by achieving the ultimate goal of clinical translation, sub-5 nm nano-constructs, in particular inorganic nanoparticles such as gold, silver, silica, and iron oxide nanoparticles, have been developed in recent years to improve the biocompatibility, delivery and pharmacokinetics of imaging probes and drug delivery systems, as well as in vivo theranostic applications. The emerging studies have provided new findings that demonstrated the unique size-dependent physical properties, physiological behaviors and biological functions of the nanomaterials in the range of the sub-5 nm scale, including renal clearance, novel imaging contrast, and tissue distribution. This advanced review attempts to introduce the new strategies of rational design for engineering nanoparticles with the core sizes under 5 nm in consideration of the clinical and translational requirements. We will provide readers the update on recent discoveries of chemical, physical, and biological properties of some biocompatible sub-5 nm nanomaterials as well as their demonstrated imaging and theranostic applications, followed by sharing our perspectives on the future development of this class of nanomaterials.

Inspirations of Cobalt Oxide Nanoparticle Based Anticancer Therapeutics

“…In anti-tumor treatments, the biocompatibility of nanoparticles directly affects the anti-tumor effects, which therefore reminds us that it is particularly important to further increase the biocompatibility of cobalt oxide nanoparticles. Gold nanoparticles and silica nanoparticles are considered to have good biocompatibility [45,46], but they can also be quickly eliminated in the body through the reticuloendothelial system (RES). Some researchers have improved the biocompatibility of gold nanoparticles by modifying them with marine carbohydrates [47,48].…”

“…Neuroblastoma (NBL) is a malignant tumor caused by the failure of embryonic neural crest cells to differentiate. As NBL patients are very young, always infants, and more than three-quarters of NBL cases are diagnosed before the age of five [46], the commonly used chemotherapy drug for adult cancer treatment is very inappropriate for these cases. At present, cisplatin is a relatively common clinical treatment against cancers, including NBL [62].…”

Excretable, ultrasmall hexagonal NaGdF4:Yb50% Nanoparticles for bimodal imaging and radiosensitization

“…[8] Thus, the development of ultrasmall, biocompatible, multifunctional nanoparticles is of high interest for potential clinical use. [8][9][10] One of the promising applications of theranostic nanoparticles is their ability to enhance radiotherapeutic e cacy. Radiation therapy (RT) is an integral part of clinical management of most solid tumors, and remains one of the most cost-effective treatments for cancer patients.…”

Excretable, ultrasmall hexagonal NaGdF4:Yb50% Nanoparticles for bimodal imaging and radiosensitization

“…[7] Thus, the development of ultrasmall, biocompatible, multifunctional nanoparticles is of high interest for potential clinical use. [7,12,13] One of the promising applications of theranostic nanoparticles is their ability to enhance radiotherapeutic e cacy. Radiation therapy (RT) is an integral part of the clinical management of most solid tumors, and remains one of the most cost-effective treatments for cancer patients.…”