Autophagy inhibition could hinder the underlying protective mechanisms in the course of
tumor treatment. The advances in autophagy inhibition have driven focus on the functionalized nanoplatforms by combining the current treatment paradigms with complementary autophagy inhibition for enhanced efficacy. Furthermore, Ca2+ overload is also a promising adjuvant target for the
tumor treatment by augmenting mitochondrial damage. In this view, complementary mitochondrial Ca2+ overload and autophagy inhibition were first demonstrated as a novel strategy suitable for homing in on the shortage of
photodynamic therapy (
PDT). We constructed biodegradable
tumor-targeted inorganic/organic hybrid nanocomposites (DPGC/OI) synchronously encapsulating IR780 and
Obatoclax by biomineralization of the nanofilm method, which consists of pH-triggered
calcium phosphate (CP), long circulation
phospholipid block copolymers 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (
DSPE)-poly(
ethylene glycol) (PEG)2000-glucose (DPG). In the presence of the hydrophilic PEG chain and
glucose transporter 1 (Glut-1)
ligands, DPGC would become an effectively
tumor-oriented nanoplatform. Subsequently, IR780 as an outstanding
photosensitizer could produce increased amounts of toxic
reactive oxygen species (ROS) after
laser irradiation.
Calcium phosphate (CP) as the Ca2+ nanogenerator could generate Ca2+ at low pH to induce mitochondrial Ca2+ overload. The dysfunction of mitochondria could enhance increased amounts of ROS. Based on the premise that autophagy would degrade dysfunctional organelles to sustain metabolism and homeostasis, which might participate in resistance to
PDT,
Obatoclax as an autophagy inhibitor would hinder the protective mechanism from
cancer cells with negligible toxicity. Such an enhanced
PDT via mitochondrial Ca2+ overload and autophagy inhibition could be realized by DPGC/OI.