Acidity/carbon dioxide-sensitive triblock polymer-grafted photoactivated vesicles for programmed release of chemotherapeutic drugs against glioblastoma

Abstract

Controllable release of chemotherapeutic drugs in tumor sites remains a big challenge for precision therapy. Herein, we developed acidity/carbon dioxide (H⁺/CO₂)-sensitive poly (ethylene glycol)-b-poly (2-(diisopropylamino) ethyl methacrylate)-b-polystyrene triblock polymer (PEG-b-PDPA-b-PS) grafted photoactivated vesicles for programmed release of chemotherapeutic drugs against glioblastoma. In brief, gold nanoparticles (GNPs) were firstly tethered with the H⁺/CO₂-sensitive PEG-b-PDPA-b-PS polymer. Next, the CO₂ precursor (ammonium bicarbonate, NH₄HCO₃) and doxorubicin (DOX) were loaded during self-assembly process of PEG-b-PDPA-b-PS-tethered GNPs, thus obtaining the multifunctional gold vesicles (denoted as GVND). The programmed multi-stimuli responsive drug release by GVND was undergone in multiple steps as follows: 1) the vesicular architecture of GVND was first swelled in tumor acidic microenvironment, 2) the GVND were partially broken under near-infrared (NIR) laser irradiation, 3) the mild hyperthermia generated by GV triggered the thermal decomposition of encapsulated NH₄HCO₃, leading to the in situ generation of CO₂, 4) the generated CO₂ reacted with PDPA of PEG-b-PDPA-b-PS, changing the hydrophilicity and hydrophobicity of GVND, thus vastly breaking its vesicular architecture, finally resulting in a "bomb-like" release of DOX in tumor tissues. Such a multi-stimuli responsive programmed drug delivery and mild hyperthermia under NIR laser activation displayed strong antitumor efficacy and completely eradicated U87MG glioblastoma tumor. This work presented a promising strategy to realize precision drug delivery for chemotherapy against glioblastoma. STATEMENT OF SIGNIFICANCE.

Keywords: Acidity/carbon dioxide-responsive; Ammonium carbonate; Chemotherapy; Glioblastoma; Photoactivated vesicles.