Dual Blood–Brain Barrier–Glioma Targeting Peptide–Poly(levodopamine) Hybrid Nanoplatforms as Potential Near Infrared Phototheranostic Agents in Glioblastoma

Combined chemo–phototherapy for boosting the efficacy of individual modalities by synergism for antiglioma treatments is in its embryonic stage and far away from effective clinical translation. Herein, moving a step closer, we recommend a facile stratagem to fabricate smart biocompatible and biodegradable multifunctional nanoplatforms comprising inherently fluorescent poly(levodopamine) nanoparticles (FLs) co-loaded with doxorubicin (DOX) and indocyanine green (ICG). The designed near-infrared (NIR) phototheranostic agents upon NIR laser irradiation helped precipitate combined chemo–phototherapy [both photothermal therapy (PTT) and photodynamic therapy (PDT)] and optical imaging under one roof. Excellent glioma-targeting ability was allocated to the nanoplatforms by conjugating them with a novel chimeric therapeutic peptide with glioma homing and antiglioma dual functionality. Further, DOX/ICG/peptide co-loaded nanoplatforms (FLDIPs) exhibited triggered drug release in response to multiple stimuli. Studies performed in 2D C6 glioma cells and 3D spheroids exhibited superior combined chemo–PDT/PTT effects (∼94% killing in cells and ∼87% in spheroids) of the designed FL based nanoplatforms compared to individual therapeutic components. Herein, the FL based multifunctional nanoplatforms with active targeting ability and stimuli responsive drug release behavior will further help in nullifying chemotherapy based adverse effects and mitigate chemo-resistance by adopting a combinatorial approach.