Nano CaCO₃ “Lysosomal Bombs” Enhance Chemotherapy Drug Efficacy via Rebalancing Tumor Intracellular pH

Abstract

Successful delivery of drugs to the target site is half the battle against tumors as intracellular alkalization pH (pHi) microenvironments severely restricted the efficacy of chemotherapy drugs delivered into tumor cells. Herein, a redox-selective pH-triggered “lysosomal bomb” (DSA/CC-DOX) is developed based on vaterite calcium carbonate and disulfide-cross-linked sodium alginate (DSA) with doxorubicin (DOX) encapsulated. Benefiting from the acid-triggered volume expansion of CaCO3, DSA/CC-DOX NPs can act like a “lysosomal bomb” that rapidly tears the lysosomal membrane with the release of acidic inclusions and the loaded DOX, and then the alkalized pHi in human liver tumor cells (HepG2) can be decreased from 7.61 to 7.09, thus promoting the intracellular accumulation of DOX nearly 3 times more than the free drug. In addition, facilitated by the responsive break of the disulfide bond to GSH, the release of DOX in HepG2 is nearly 8 times that of human normal liver cell (LO2). Notably, DSA/CC-DOX treatment increased the tumor inhibition rate of free drug by 16% and effectively reduced the cardiotoxicity of DOX in the mouse H22 liver cancer model. Overall, acidifying the tumor intracellular environment is a prospective way to improve the antitumor capacity of chemotherapy drug.

Colchicine-Containing Nanoparticles Attenuates Acute Myocardial Infarction Injury by Inhibiting Inflammation

“…However, in clinical work, intracardiac injection of drugs is risky and di cult to operate. Our previous study showed that taking advantage of the acidi cation of intracellular pH by calcium carbonate nanoparticle, the e cacy of the loaded DOX was remarkably improved, and its toxicity was signi cantly reduced [13]. Therefore, in this study, colchicine was encapsulated into calcium carbonate nanoparticles, which, on the one hand, reduced adverse reactions, and on the other hand, increased the therapeutic effect.…”

Colchicine-Containing Nanoparticles Attenuates Acute Myocardial Infarction Injury by Inhibiting Inflammation

“…Our previous study showed that taking advantage of the acidi cation of intracellular pH by calcium carbonate nanoparticle, the e cacy of the loaded DOX was remarkably improved, and its toxicity was signi cantly reduced [13]. Therefore, in this study, colchicine was encapsulated into calcium carbonate nanoparticles, which, on the one hand, reduced adverse reactions, and on the other hand, increased the therapeutic effect.…”

Rotatable Aggregation‐Induced‐Emission/Aggregation‐Caused‐Quenching Ratio Strategy for Real‐Time Tracking Nanoparticle Dynamics

“…A similar faster breaking process (Figure S10, Supporting Information) was displayed in human liver tumor cells (HepG2 cells), due to a higher GSH express of HepG2 cells than U‐251 cells (Figure S9, Supporting Information). [ 37 ]…”