Hybrid Membrane Biomimetic Photothermal Nanorobots for Enhanced Chemodynamic-Chemotherapy-Immunotherapy

Abstract

Glioblastoma multiforme (GBM) is a highly invasive and fatal brain tumor with a grim prognosis, where current treatment modalities, including postoperative radiotherapy and temozolomide chemotherapy, yield a median survival of only 15 months. The challenges of tumor heterogeneity, drug resistance, and the blood–brain barrier necessitate innovative therapeutic approaches. This study introduces a strategy employing biomimetic magnetic nanorobots encapsulated with hybrid membranes derived from platelets and M1 macrophages to enhance blood–brain barrier penetration and target GBM. The nanorobots encapsulate a polypyrrole/Fe 3 O 4 nanocomplex (PPy@F) for photothermal therapy (PTT) and promote the Fenton reaction of Fe 3 O 4 to generate chemodynamic therapy (CDT). Additionally, temozolomide and PD-L1 antibody (SNTSESF) act as chemotherapy drug and immune checkpoint inhibitor, respectively. The biomimetic design leverages the functional properties of cell membranes to improve the blood residence time and tumor targeting. The integration of PTT and CDT aims to transform “cold” tumors into “hot” tumors, thereby enhancing immunotherapeutic efficacy. This multifaceted approach, PTT, CT, CDT, and immune checkpoint blockade therapy, offers a promising strategy for the treatment of GBM.