Overcoming Hurdles in Nanoparticle Clinical Translation: The Influence of Experimental Design and Surface Modification

Abstract

Nanoparticles are becoming an increasingly popular tool for biomedical imaging and drug delivery. While the prevalence of nanoparticle drug-delivery systems reported in the literature increases yearly, relatively little translation from the bench to the bedside has occurred. It is crucial for the scientific community to recognize this shortcoming and re-evaluate standard practices in the field, to increase clinical translatability. Currently, nanoparticle drug-delivery systems are designed to increase circulation, target disease states, enhance retention in diseased tissues, and provide targeted payload release. To manage these demands, the surface of the particle is often modified with a variety of chemical and biological moieties, including PEG, tumor targeting peptides, and environmentally responsive linkers. Regardless of the surface modifications, the nano–bio interface, which is mediated by opsonization and the protein corona, often remains problematic. While fabrication and assessment techniques for nanoparticles have seen continued advances, a thorough evaluation of the particle’s interaction with the immune system has lagged behind, seemingly taking a backseat to particle characterization. This review explores current limitations in the evaluation of surface-modified nanoparticle biocompatibility and in vivo model selection, suggesting a promising standardized pathway to clinical translation.

Redox-responsive nanoplatform for codelivery of miR-519c and gemcitabine for pancreatic cancer therapy

“…In conclusion, the key hurdles of the clinical translation of nanomedicine are biological barriers, large-scale manufacturing, biocompatibility, and safety (40,41). The characterization of our combination micelles shows sufficient drug loading of GEM and miRNA, redox-responsive release of GEM, and controlled release of miRNA.…”

Functionalized Graphene Oxide for Chemotherapeutic Drug Delivery and Cancer Treatment: A Promising Material in Nanomedicine

“…Among these, oral and intravenous administration are the two most common routes of administration of NPs. Concerning the administration of nanoparticles via inhalation, the barriers to drug delivery include clearance in the upper airway by ciliated epithelial cells and in the lower airway by lung-associated macrophages [ 55 ]. The oral administration of a dug through encapsulating NPs, in general, improves drug bioavailability because of enhanced permeation and absorption of nanomaterials.…”

“…Orally administered NPs encapsulate and protect the acid-sensitive or peptidomimetic drug against chemical and metabolic degradation in the gastrointestinal tract, and enable controlled and systemic release of drugs. Nanoparticle formulation further improves the delivery of poorly water-soluble drugs, mediates transcytosis across the tight intestinal barrier, reduces transporter-mediated efflux of drugs, and enables intracellular and transcellular delivery of large macromolecules [ 54 , 55 ]. Nanoparticle therapeutics also reduce the hepatic first-pass effect of oral medications.…”

“…Size is one of the most critical factors that control the circulatory residence time and uptake of NPs by the RES. It has been shown that NPs sized >40 nm are cleared slowly (6 months), while NPs <15 nm are cleared within 24 h [ 55 ]. Notably, small-sized particles <5 nm after undergoing rapid uptake in the liver and spleen are also rapidly removed by kidneys.…”

Editorial of Special Issue “Surface-Functionalized Nanoparticles as Drug Carriers”

“…Finally, Shreffler et al [20] comprehensively review the primary challenges for translating nanomedicines into the clinic. The nanoparticle-immune system interactions often result in the rapid clearance of the nanoparticles and impose an obstacle for the clinical translation of nanoparticle-based systems.…”