Biomimetic targeting magnetite hollow nanostructures based on pH-responsive benzoic-imine bonds for antitumor activity

• Published in: Journal of industrial and engineering chemistry (Seoul, Korea) Vol. 123; pp. 371 - 381
• Main Authors: Kunene, Sikhumbuzo Charles, Lin, Kuen-Song, Weng, Meng-Tzu, Carrera Espinoza, Maria Janina, Lin, You-Sheng, Lin, Yi-Ting
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 25.07.2023; 한국공업화학회
• Subjects: Cell membrane; Homotypic-targeting; Magnetite hollow nanostructures; PEGylated; pH-responsive; 화학공학; Cell membrane; XANES; DMSO; EPR; DL; FT-IR; DLS; APTES; XRD; Homotypic-targeting; MTT; EXAFS; DR; HR-TEM; Magnetite hollow nanostructures; PEGylated; PBS; MHNs; SQUID; CM; DOX; BET; HCL; USFDA; SDS-PAGE; PEG; pH-responsive; FE-SEM; TEM; MHNCs
• ISSN: 1226-086X; 1876-794X
• DOI: 10.1016/j.jiec.2023.03.054

[Display omitted] •pH-responsive nanostructures were formed via benzoic imine covalent bonds.•Cancer CM functionalization offers a nanosystem with homotypic-targeting ability.•High DOX was released at pH 5.5 and low drug release under pH 7.4.•PEG and CM improved tumors cellular uptake via EPR and homotypic-recognition.•MHNC–DOX–PEG/CM displayed antitumor effect with lower tumor volumes. In this study, versatile homotypic-targeting and PEGylated magnetite hollow nanostructures (MHNs) that are pH-responsive used as doxorubicin (DOX) nanocarriers are demonstrated. Cancer cell membrane (CM) and polyethylene glycol (PEG) functionalization through benzoic imine bonds endows DOX-conjugated nanocarriers with enhanced tumor accumulation and penetration, biomimetic-targeting specificity, as well as on-demand drug release, which improves their antitumor efficacy. The characteristic diffraction peaks of magnetite nanocarriers at 35° indexed as (311) plane of magnetite can be observed. Hierarchical mesoporous nanostructures with specific pore size distributions of approximately 99.9, 97.2, and 95.6%, were developed. In vitro studies revealed that drug-free nanostructures exhibited excellent biocompatibility with more than 95% cell viability. In contrast, drug-conjugated nanostructures demonstrated high therapeutic effect, pH-responsive drug release, and enhanced intracellular uptake in HepG2 cells. In vivostudies showed that the MHNC–DOX–PEG/CM formulations displayed the best antitumor efficacy, with the lowest tumor volume and weight. Furthermore, significantly large apoptotic and necrotic areas were identified in the tumor tissues from the DOX-conjugated groups, but no noticeable inflammation or hemorrhage was observed in the main organs. Therefore, these results suggest that the formulated nanostructures have great potential for cancer therapies.