ATP-Decorated Mesoporous Silica for Biomineralization of Calcium Carbonate and P2 Purinergic Receptor-Mediated Antitumor Activity against Aggressive Lymphoma

Abstract

Adenosine triphosphate (ATP) is an important transmitter that mediates various biological effects via purinergic receptors (P2 receptors) in cancer. We investigated the antitumor activity of ATP-decorated and doxorubicin (DOX)-loaded mesoporous silica with biomineralization of calcium carbonate against a highly aggressive and metastatic murine lymphoma called Dalton's lymphoma (DL). Our results suggest that this nanocomposite has unique effects with respect to the morphology and properties of calcium carbonate on the surface of the nanoparticle. DOX in the nanoparticles was prevented from quick release via the interactions of the phosphate group present on ATP and calcium carbonate. This construct is significantly tumoricidal against parental and DOX-resistant DL cells and is thus a promising candidate for applications in drug delivery. The composite nanomaterial has excellent biocompatibility with higher uptake and acts via the participation of the purinergic receptor P2X7. The nanocomposite induces significantly higher apoptosis in tumor cells compared with DOX alone. Treatment of DL-bearing mice with the construct significantly reduces tumor burden, in addition to augmenting the lifespan of tumor-bearing mice as demonstrated by a sustained healthy life of the animals and improved histopathological parameters.

P2X7 Receptor in Hematological Malignancies

“…Additional research showing a relationship between P2X7 and lymphoma concerns an aggressive and metastatic murine form of this neoplasm called Dalton's lymphoma (DL). The authors tested the antitumoral effect of silica particles carrying ATP plus doxorubicin and designed to target cancer in a pH-dependent fashion on DL growth and progression (Srivastava et al, 2018). Srivastava et al (2018) demonstrated a good efficiency of the particles in reducing lymphoma burden and increasing overall survival of lymphoma-bearing mice, suggesting that this effect will be mediated by upregulation of P2X7 receptor and consequent cytotoxicity.…”

Biomineralization Forming Process and Bio-inspired Nanomaterials for Biomedical Application: A Review

“…Adenosine triphosphate (ATP), an existence form of energy, was found to mediate drug-liberating process during cancer therapy, and to be acted as an antineoplastic agent in vitro [76]. Based on this, S.P., et al (2018) [75] synthesized an ATP-loaded nanocomposite with pronounced apoptosis in tumor cells. First, mesoporous silica nanoparticles (MSNPs), a biocompatible deliver, was decorated with ATP on the surface.…”

New Advances in In Vivo Applications of Gated Mesoporous Silica as Drug Delivery Nanocarriers

“…Srivastava et al developed adenosine triphosphate (ATP)‐functionalized MSNs with a calcium carbonate coating for cancer drug delivery against aggressive lymphoma ( Figure ) . ATP could serve as modulator ligand binding purinergic receptors (P2 receptors), which are overexpressed in diverse cancer cells types thus suppressing tumor cell growth.…”