Boosting nutrient starvation-dominated cancer therapy through curcumin-augmented mitochondrial Ca2+ overload and obatoclax-mediated autophagy inhibition as supported by a novel nano-modulator GO-Alg@CaP/CO

Abstract

Background By hindering energy supply pathway for cancer cells, an alternative therapeutic strategy modality is put forward: tumor starvation therapy. And yet only in this blockade of glucose supply which is far from enough to result in sheer apoptosis of cancer cells. Results In an effort to boost nutrient starvation-dominated cancer therapy, here a novel mitochondrial Ca2+ modulator Alg@CaP were tailor-made for the immobilization of Glucose oxidase for depriving the intra-tumoral glucose, followed by the loading of Curcumin to augment mitochondrial Ca2+ overload to maximize the therapeutic efficiency of cancer starvation therapy via mitochondrial dysfunctions. Also, autophagy inhibitors Obatoclax were synchronously incorporated in this nano-modulator to highlight autophagy inhibition. Conclusion Here, a promising complementary modality for the trebling additive efficacy of starvation therapy was described for cutting off the existing energy sources in starvation therapy through Curcumin-augmented mitochondrial Ca2+ overload and Obatoclax-mediated autophagy inhibition. Graphical Abstract

Nanorod/nanodisk‐integrated liquid crystalline systems for starvation, chemodynamic, and photothermal therapy of cancer

“…ATP assay was conducted for assessing the catalytic potential of designed hybrid gel system (Figure S16). GOx‐treated group exhibited distinct reduction of intracellular ATP level compared to control (no treatment) group 75 . CNC/ICG/GOx/Cu/LAP + NIR group also displayed significant decrease in the intracellular ATP level by the glucose deprivation of GOx.…”

“…GOx-treated group exhibited distinct reduction of intracellular ATP level compared to control (no treatment) group. 75 CNC/ICG/GOx/Cu/LAP + NIR group also displayed significant decrease in the intracellular ATP level by the glucose deprivation of GOx. It suggests that the bioactivity of incorporated GOx in the gel structure is appropriately maintained for ST. Of note, the combination of CDT/PTT with ST (as shown in CNC/ICG/GOx/Cu/LAP + NIR group) further reduced intracellular ATP level as reported.…”

Harnessing bioactive nanomaterials in modulating tumor glycolysis-associated metabolism

“…The results are consistent with another report in which HSP inhibitor and GOx together enhanced the efficacy of mild-temperature PTT [ 119 ]. It has been demonstrated that Ca .2+ overload-induced mitochondrial disruption promotes autophagy [ 120 ]. Wang et al reported the blockade of autophagosome degradation via obatoclax could inhibit ATP release, synergizing with GOx to cut off energy sources in starvation therapy [ 120 ].…”

“…It has been demonstrated that Ca .2+ overload-induced mitochondrial disruption promotes autophagy [ 120 ]. Wang et al reported the blockade of autophagosome degradation via obatoclax could inhibit ATP release, synergizing with GOx to cut off energy sources in starvation therapy [ 120 ].

Fig.

…”

Advances in Nanodelivery Systems Based on Metabolism Reprogramming Strategies for Enhanced Tumor Therapy

“…Glucose reprogramming strategies reduced tumor energy and material supply by blocking tumor glucose uptake, robbing glucose and inhibiting glycolysis, etc . The lactic acid metabolism reprogramming strategy improved the tumor microenvironment (TME) by depleting high levels of lactate. , The lipid metabolism reprogramming strategy inhibited tumor proliferation by reducing the material supply of prostate cancer and lymphoma, inhibiting angiogenesis, increasing the formation of lipid peroxides, etc. , The amino acid metabolism reprogramming strategy destroyed the tumor’s self-protection system by depleting glutamine, GSH, and cysteine overexpressed in the tumors, as well as inhibiting the production of these amino acids, thereby rendering the tumor more vulnerable. − The metal ion reprogramming strategy promoted tumor apoptosis through interfering with ion homeostasis, reacting with metabolite H 2 O 2 to generate additional cytotoxic hydroxyl radicals (•OH), and inducing mitochondrial damage. , To sum up, metabolism reprogramming strategies holded promise for enhanced tumor therapy.…”