Modified Aerotaxy for the Plug-in Manufacture of Cell-Penetrating Fenton Nanoagents for Reinforcing Chemodynamic Cancer Therapy

Abstract

The assemblies of anisotropic nanomaterials have attracted considerable interest in advanced tumor therapeutics because of the extended surfaces for loading of active molecules and the extraordinary responses to external stimuli for combinatorial therapies. These nanomaterials were usually constructed through templated or seed-mediated hydrothermal reactions, but the lack of uniformity in size and morphology, as well as the process complexities from multiple separation and purification steps, impede their practical use in cancer nanotherapy. Gas-phase epitaxy, also called aerotaxy (AT), has been introduced as an innovative method for the continuous assembly of anisotropic nanomaterials with a uniform distribution. This process does not require expensive crystal substrates and high vacuum conditions. Nevertheless, AT has been used limitedly to build high-aspect-ratio semiconductor nanomaterials. With these considerations, a modified AT was designed for the continuous in-flight assembly of the cell-penetrating Fenton nanoagents (Mn–Fe CaCO3 (AT) and Mn–Fe SiO2 (AT)) in a single-pass gas flow because cellular internalization activity is essential for cancer nanotherapeutics. The modified AT of Mn–Fe CaCO3 and Mn–Fe SiO2 to generate surface nanoroughness significantly enhanced the cellular internalization capability because of the preferential contact mode with the cancer cell membrane for Fenton reaction-induced apoptosis. In addition, it was even workable for doxorubicin (DOX)-resistant cancer cells after DOX loading on the nanoagents. After combining with immune-checkpoint blockers (antiprogrammed death-ligand 1 antibodies), the antitumor effect was improved further with no systemic toxicity as chemo-immuno-chemodynamic combination therapeutics despite the absence of targeting ligands and external stimuli.

Tuning the Emission of a Nonconventional Aggregation-Induced Emission Polymer via Silicon-Bridged Twisted Intramolecular Charge Transfer for Targeted Delivery and Visualized Drug Release

“…The presence of multiple cavities in the hyperbranched structures makes them potential drug carriers for controlled drug delivery and release. To evaluate the drug loading and releasing capabilities of HBPSi-Apt, DOX, a clinically used anticancer drug, is selected as the model drug. , As can be seen in Figure S26, HBPSi-Apt exhibits concentration-dependent DOX loading behavior, and the maximum loading capacity reaches 611.48 mg/g when exposed to a 0.35 mg/mL DOX solution. Considering that the negatively charged AS1411 aptamer may combine with DOX and thus block the cell-targeting capability of aptamers, we tested the DOX loading capacity of equivalent HBPSi.…”

Advantages of Nanomedicine in Cancer Therapy: A Review

“…This system produced Mn−Fe spike-decorated amorphous CaCO 3 (termed Mn−Fe CaCO 3 (AT)) and SiO 2 (termed Mn−Fe CaCO 3 (AT)) nanoagents for chemodynamic cancer therapies in a continuous, single-pass configuration. 47 Notably, surfaces after AT showcased increased roughness, affecting internalization behavior. The comparison between nanoagents and composite precursor particles using epithelial tumor cells revealed higher internalization rates for nanoagents (after AT) under both normoxic and hypoxic conditions (Figure 5C).…”

“…Internalization of coumarin-6-loaded nanoagents into epithelial tumor cells (C). Reproduced with permission from ref . Copyright 2022 American Chemical Society.…”

Approved Nanomedicine against Diseases

“…In addition, through codelivery, the advantages of synergistic therapy can be improved and compromise drug resistance [ 8 ]. Nanomedicine has obtained breakthroughs in cancer treatment, diagnosis, and gene delivery [ 9 , 10 , 11 , 12 , 13 ], as more than 90 nanoformulations were marketed [ 14 , 15 , 16 ].…”