Biodegradable mesoporous manganese carbonate nanocomposites for LED light-driven cancer therapy via enhancing photodynamic therapy and attenuating survivin expression

Lihua Li,Xianfeng Yang,Xiaoming Wei,Zefeng Lin,Ling Huang,Xiangling Ye,Lingling Chen,Zhongmin Yang

doi:10.1186/s12951-021-01057-2

Abstract

Triple-negative breast cancer (TNBC) is one of the most daunting diseases, low toxicity and efficient approaches are in urgent demand. Herein, we developed degradable mesoporous manganese carbonate nanocubes (MnCO3 NCs), incorporated with survivin shRNA-expressing plasmid DNA (iSur-pDNA) and riboflavin (Rf), namely MRp NCs, for synergistic TNBC therapy. The MnCO3, itself, could generate O2 and CO2 under H2O2 and thus relieve the hypoxia and acidic tumor microenvironment (TME). Furthermore, the MnCO3 NCs exhibited high Rf loading capacity and iSur-pDNA delivery ability after polyethyleneimine modification. Specifically, MRp NCs decompose in TME, meanwhile they deprived the endogenous expression of survivin gene and significantly amplified the generation of reactive oxygen species after exposure to LED light, resulting in serious tumor destruction. The multifunctional MRp NCs with LED light-driven characters are able to provide a high efficiency, low toxicity and promising strategy for TNBC therapy.

Highlights

Triple-negative breast cancer (TNBC) is an important and intractable subtype of breast cancer due to the lack of biomarkers and its high metastasis [1]
We developed M nCO3/Rf/ pDNA nanocomposites which consisted of mesoporous MnCO3 nanocubes (NCs) loading with riboflavin (Rf ) and survivin shRNA expressing plasmid for combined TNBC therapy
Characterization of MRp NCs Firstly, the monodisperse MnCO3 NCs were prepared by a microemulsion method according to our previous method [19]

Summary

Introduction

Triple-negative breast cancer (TNBC) is an important and intractable subtype of breast cancer due to the lack of biomarkers and its high metastasis [1]. Biodegradation of MnCO3 in TME simulation solution PEI-MnCO3 NCs were incubated in a solution of PBS (pH = 6.5) containing 2 mM H 2O2 for 3, 12 and 24 h, respectively. The 4T1 cells were treated with PEI-MnCO3 NCs (50 μg mL−1) as experiment group and medium as control group, the cells were cultured with BCECF AM (5 μM) for 20 min, and their images were observed under fluorescence microscopy.

Results

Conclusion