Biomimetic Upconverting Nanoplatforms for Glioblastoma Bioimaging and Targeted Therapy

Glioblastoma (GB) is an aggressive and fast-progressing brain tumor with high recurrence rates and poor patient survival. Its resistance to conventional treatments and limited therapeutic options highlight the urgent need for innovative strategies to improve outcomes. In this scenario, we present a multifunctional biomimetic nanoplatform designed for targeted therapy and bioimaging of GB. The system comprises core–shell upconverting nanoparticles (UCNPs) coated with a mesoporous silica (UCNP@mSiO2), loaded with the chemotherapeutic agent temozolomide (TMZ), and cloaked with U251 GB cell membranes (BUCNP:TMZ). The mesoporous silica shell enhances stability and drug-loading capacity, while the membrane coating improves colloidal stability, immune evasion, and homotypic targeting. The UCNP core enables real-time near-infrared (NIR) imaging under 980 nm excitation. BUCNP:TMZ exhibits an average diameter of approximately 80 nm, a TMZ encapsulation efficiency of 58.5%, and drug complete release after 4 h at pH 5.5. Cellular internalization studies demonstrated preferential uptake of BUCNP:TMZ in homologous U251 GB cells compared to nonparental U87 and nonmalignant HDFn cells. Cell-viability assays showed a concentration-dependent cytotoxic response, with BUCNP:TMZ reducing U251 viability by over 50% at 50 μg mL–1, while showing minimal toxicity toward HDFn fibroblasts. This multifunctional nanoplatform integrates targeted delivery, NIR bioimaging, and sustained drug release into a single construct, offering a promising approach for GB theranostics.