Enzyme-catalyzed synthesis of selenium-doped manganese phosphate for synergistic therapy of drug-resistant colorectal cancer

Abstract

Background The development of multidrug resistance (MDR) during postoperative chemotherapy for colorectal cancer substantially reduces therapeutic efficacy. Nanostructured drug delivery systems (NDDSs) with modifiable chemical properties are considered promising candidates as therapies for reversing MDR in colorectal cancer cells. Selenium-doped manganese phosphate (Se-MnP) nanoparticles (NPs) that can reverse drug resistance through sustained release of selenium have the potential to improve the chemotherapy effect of colorectal cancer. Results Se-MnP NPs had an organic–inorganic hybrid composition and were assembled from smaller-scale nanoclusters. Se-MnP NPs induced excessive ROS production via Se-mediated activation of the STAT3/JNK pathway and a Fenton-like reaction due to the presence of manganese ions (Mn2+). Moreover, in vitro and in vivo studies demonstrated Se-MnP NPs were effective drug carriers of oxaliplatin (OX) and reversed multidrug resistance and induced caspase-mediated apoptosis in colorectal cancer cells. OX@Se-MnP NPs reversed MDR in colorectal cancer by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (e.g., ABCB1, ABCC1 and ABCG2). Finally, in vivo studies demonstrated that OX-loaded Se-MnP NPs significantly inhibited proliferation of OX-resistant HCT116 (HCT116/DR) tumor cells in nude mice. Conclusions OX@Se-MnP NPs with simple preparation and biomimetic chemical properties represent promising candidates for the treatment of colorectal cancer with MDR.

Gfi-1 modulates HMGB1-Mediated autophagy to overcome oxaliplatin resistance in colorectal cancer

“…Nevertheless, the pharmacological effects of Gfi1 need to be verified in vivo, which will greatly improve the findings of this study. Nanostructured drug delivery systems with modifiable chemical properties have been identified as promising candidates for reversing drug resistance in CRC [ 43 ]. In addition, tumor-associated fibroblast-derived exosomes have also been found to be associated with drug resistance [ 44 ].…”

Advancements in the Application of the Fenton Reaction in the Cancer Microenvironment

“…The research group led by Cong developed a Ru-based nanozyme with dual catalytic activities (glucose-oxidase-like activity and peroxidase-like activity). The nanozyme was loaded into nanoliposomes and modified with a tumor cell membrane to obtain Ru@ATO-Lip/M nanoparticles [ 50 , 51 ]. Ru exhibits GOx-like activity, strongly catalyzing the reaction between glucose and oxygen to generate H 2 O 2 .…”