Surface Charge of Supramolecular Nanosystems for In Vivo Biodistribution: A MicroSPECT/CT Imaging Study

Abstract

Bioimaging has revolutionized medicine by providing accurate information for disease diagnosis and treatment. Nanotechnology‐based bioimaging is expected to further improve imaging sensitivity and specificity. In this context, supramolecular nanosystems based on self‐assembly of amphiphilic dendrimers for single photon emission computed tomography (SPECT) bioimaging are developed. These dendrimers bear multiple In3+ radionuclides at their terminals as SPECT reporters. By replacing the macrocyclic 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid cage with the smaller 1,4,7‐triazacyclononane‐1,4,7‐triacetic acid scaffold as the In3+ chelator, the corresponding dendrimer exhibits neutral In3+‐complex terminals in place of negatively charged In3+‐complex terminals. This negative‐to‐neutral surface charge alteration completely reverses the zeta‐potential of the nanosystems from negative to positive. As a consequence, the resulting SPECT nanoprobe generates a highly sought‐after biodistribution profile accompanied by a drastically reduced uptake in liver, leading to significantly improved tumor imaging. This finding contrasts with current literature reporting that positively charged nanoparticles have preferential accumulation in the liver. As such, this study provides new perspectives for improving the biodistribution of positively charged nanosystems for biomedical applications.

Self-Assembling Supramolecular Dendrimers for Biomedical Applications: Lessons Learned from Poly(amidoamine) Dendrimers

“…Figure 11 illustrates amphiphilic dendrimers 11-12, which we conceived and developed to construct supramolecular dendrimer nanoprobes for SPECT and PET imaging. 2,18,19 The first ever supramolecular dendrimer nanoprobe for SPECT imaging was formed from 11. 18 This dendrimer is composed of a Figure 11B, left panel), which accumulated effectively within the tumor via the EPR effect for SPECT imaging (Figure 11C, left panel).…”

“…By employing different small and simple amphiphilic building units, we have successfully constructed various supramolecular dendrimers for the delivery of drugs, nucleic acid therapeutics, and bioimaging agents. [1][2][3][4][5][18][19][20][21][22][23][24][25][26][27] It is worth mentioning that amphiphilic dendrimers can also readily self-assemble into vesicle structures known as "dendrimersomes". 28,29 The dendrimersome concept-which differs from the supramolecular dendrimer concept described in the present work-was inaugurated by Percec et al, 28 and has been investigated extensively as a means of mimicking membranes in biological applications.…”

Dendrimer-decorated nanogels: Efficient nanocarriers for biodistribution in vivo and chemotherapy of ovarian carcinoma

“…The ovarian carcinoma, especially, having the highest mortality rate in gynecological cancers, is difficult to theranostics drawing support from nanoplatforms due to its dense extracellular matrix [ 7 , 8 ]. In recent years, some novel nanocarriers have been designed by optimizing their physicochemical properties, such as size, softness, shape, surface charge and modification, to achieve highly efficient delivery, to improve theranostic efficacy and reduce systemic toxicity [ [9] , [10] , [11] , [12] , [13] ].…”

Safety Evaluation of Nanotechnology Products

“…Surface charge can substantially influence the efficiency and the in vivo fate of NPs [ 266 , 267 ]. The surface densities and charges (negative, neutral, or positive) are different for each NP.…”