Nano Enabled Dual-Responsive Drug Carrier Originated from Acetalated Dextran/Carboxylated Nanocellulose-Based Core–Shell Microspheres

Magneto-photoresponsive polymeric microspheres represent a promising platform for targeted, externally triggered drug delivery. However, achieving precise control while minimizing phototoxicity remains a major challenge. In this study, we developed biodegradable core–shell microspheres composed of acetalated dextran (AcD) and cellulose modified by citric acid (CMC), co-loaded with a photoacid generator (PAG), Fe 3 O 4 nanoparticles, and zerovalent iron (ZVI). These components enable dual-stimuli responsiveness, in which short UV exposure (365 nm, 10 min on/off cycles) and an alternating magnetic field (AMF, 150 Oe) act synergistically to enhance photoacid generation and trigger rapid drug release. Upon dual stimulation, the system exhibited rapid release kinetics, with cumulative release reaching ∼98% for curcumin within 45 min and ∼98% for doxorubicin (DOX) within 60 min. Cytocompatibility studies showed minimal toxicity toward healthy HEK293 cells, while DOX-loaded microspheres reduced viability of HepG2 liver cancer cells to ∼14% after 24 h. In 3D MCF-7 spheroid models, DOX-loaded microspheres induced significant spheroidal disintegration and a ∼41% reduction in acid phosphatase activity over 21 days. This work demonstrates a programmable, biodegradable, magneto-photoresponsive microsphere system capable of efficient and tumor-selective drug delivery, offering great potential for next-generation localized chemotherapy applications.