Preparation and In Vitro Evaluation of the DOX@Mem-HMnO2 Bioinspired Nanosystem: A Proof-of-Concept Study

IntroductionCell 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-HMnO₂ nanosystem based on hollow mesoporous manganese dioxide (HMnO₂) 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.MethodsMonodisperse silica nanoparticles were synthesized via a modified Stöber method as sacrificial templates to prepare hollow mesoporous HMnO₂. DOX was loaded into HMnO₂, and native A549 cell membrane was isolated by differential centrifugation and wrapped onto DOX-loaded HMnO₂. 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).ResultsDOX@Mem-HMnO₂ 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 HMnO₂) 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-HMnO₂ produced significantly stronger anti-proliferative and anti-migratory effects than free DOX and DOX@HMnO₂ (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.ConclusionDOX@Mem-HMnO₂ 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.