Deep Drug Penetration of Nanodrug Aggregates at Tumor Tissues by Fast Extracellular Drug Release

Abstract

Herein, a new nanodrug of azobenzene-functionalized interfacial cross-linked reverse micelles (AICRM) with 5-fluorouracil loading (5-FU@AICRM) is reported. Upon irradiation with 530 nm light in water, the surface azobenzenes of the nanoparticles change from polar cis-conformation to nonpolar trans-conformation, resulting in the aggregation of 5-FU@AICRM within minutes. Simultaneously, the conformation change unlocks hydrophilic 5-FU with a strong water immigration propensity, allowing them to spray out from the AICRM quickly. This fast release ensures a thorough release of the drug, before the aggregates are internalized by adjacent cells, making it possible to achieve deep tissue penetration. A study of in vivo anticancer activity in A549 tumor-bearing nude mice shows that the tumor inhibition rate (TIR) of 5-FU@AICRM is up to ≈86.2%, 31.6% higher than that of group without green light irradiation and 20.7% higher than that of carmofur (CF, a hydrophobic analog of 5-FU)-loaded AICRM (CF@AICRM), in which CF is released slowly under light irradiation because of its hydrophobicity. Fast drug release upon nanodrug aggregation provides a good solution for balancing the contradiction of "aggregation and penetration" in tumor treatment with nanodrugs.

Metronidazole and Ketoprofen-Loaded Mesoporous Magnesium Carbonate for Rapid Treatment of Acute Periodontitis In Vitro

“…Yao and co-workers loaded 5-fluorouracil into azobenzene-functionalized interfacial cross-linked reverse micelles, relying on the high permeability of small molecules for drug delivery. Although this strategy enhanced the local drug accumulation, it failed to consider the poor solubility of the insoluble drug itself . However, recent studies have revealed that the crystallization of drugs could be restrained when they are embarked into mesoporous holes with pore diameters, ranging from 2 to 50 nm .…”

“…Although this strategy enhanced the local drug accumulation, it failed to consider the poor solubility of the insoluble drug itself. 19 However, recent studies have revealed that the crystallization of drugs could be restrained when they are embarked into mesoporous holes with pore diameters, ranging from 2 to 50 nm. 20 Mesoporous magnesium carbonate (MMC) has recently been synthesized, exhibiting a narrow distribution of pore sizes and a wide superficial area.…”

Surface-Charge-Switchable and Size-Transformable Thermosensitive Nanocomposites for Chemo-Photothermal Eradication of Bacterial Biofilms in Vitro and in Vivo

“…Multifunctional antibacterial nanomaterials, such as polymeric micelles, liposomes, inorganic nanomaterials, and nanocomposites, have attempted to treat pathogenic infections and eradicate mature biofilms. − Antibiotics usually disinfect bacteria through a chemical process by targeting specific cellular components; however, these microorganisms easily develop resistance by gene or phenotype mutation. , On the other hand, near-infrared (NIR)-light-induced photothermal therapy (PTT) kills bacteria by a physical mechanism with outstanding advantages, such as nonreleasing properties, zero drug resistance, and noninvasive therapy . More importantly, PTT-induced hyperthermia can weaken the integrity of bacterial cell membranes and prompt drug absorption. , Therefore, synergistic bactericidal systems were recently designed by combining antibiotic therapy with PTT-induced hyperthermia. , With high chemical stability and excellent biocompatibility, gold nanorods (GNRs) have been widely used with antibacterial agents in photothermal therapy. , Although nanomaterials with photothermal effects can produce local heat under NIR laser irradiation, the distance of thermal radiation is limited.…”