Preparation and In Vitro Evaluation of the DOX@Mem-HMnO2 Bioinspired Nanosystem: A Proof-of-Concept Study
Jiangang Chen, Ao Xu, Yusheng Tang, Zhen Yang, Shibo Gao, Yan ZhangIntroduction
Cell membrane–coated nanoparticles are emerging as promising biomimetic platforms for targeted cancer drug delivery, owing to their homotypic tumor-targeting ability and favorable biocompatibility. In this study, we fabricated a biomimetic DOX@Mem-HMnO 2 nanosystem based on hollow mesoporous manganese dioxide (HMnO 2 ) coated with A549 lung adenocarcinoma cell membrane (Mem) and loaded with doxorubicin (DOX), and evaluated its in vitro biological performance using the A549 cell model.
Methods
Monodisperse silica nanoparticles were synthesized via a modified Stöber method as sacrificial templates to prepare hollow mesoporous HMnO 2 . DOX was loaded into HMnO 2 , and native A549 cell membrane was isolated by differential centrifugation and wrapped onto DOX-loaded HMnO 2 . SEM and TEM characterized morphology and membrane coating; UV-Vis spectrophotometry confirmed DOX loading; particle size and zeta potential were measured, and colloidal stability was monitored over 72 h in deionized water and DMEM. CCK-8 and Transwell assays evaluated anti-proliferative and anti-migratory effects (≥3 independent replicates).
Results
DOX@Mem-HMnO 2 was successfully prepared as spherical, relatively monodisperse nanoparticles with an observable membrane-like outer layer and retained DOX characteristic absorbance. Zeta potential shifted from −42.1 ± 1.8 mV (bare HMnO 2 ) to −23.8 ± 1.5 mV after membrane coating and −30.2 ± 1.6 mV after DOX loading. The nanosystem remained stable without aggregation over 72 h. All DOX-containing groups inhibited A549 proliferation in a concentration-dependent manner; DOX@Mem-HMnO 2 produced significantly stronger anti-proliferative and anti-migratory effects than free DOX and DOX@HMnO 2 (P < 0.05), while empty carriers showed low intrinsic cytotoxicity. This study is limited to in vitro A549 experiments; direct evidence for homotypic targeting and in vivo performance is absent.
Conclusion
DOX@Mem-HMnO 2 can be readily synthesized with uniform morphology, favorable colloidal stability, and enhanced in vitro anti-proliferative and anti-migratory activity against A549 cells, providing a proof-of-concept basis for further biological validation.