Biomimetic liposomal nanozymes improve breast cancer chemotherapy with enhanced penetration and alleviated hypoxia

Abstract

Background Doxorubicin (Dox) has been recommended in clinical guidelines for the standard-of-care treatment of breast cancer. However, Dox therapy faces challenges such as hypoxia, acidosis, H2O2-rich conditions and condensed extracellular matrix in TME as well as low targeted ability. Methods We developed a nanosystem H-MnO2-Dox-Col NPs based on mesoporous manganese dioxide (H-MnO2) in which Dox was loaded in the core and collagenase (Col) was wrapped in the surface. Further the H-MnO2-Dox-Col NPs were covered by a fusion membrane (MP) of inflammation-targeted RAW264.7 cell membrane and pH-sensitive liposomes to form biomimetic MP@H-MnO2-Dox-Col for in vitro and in vivo study. Results Our results shows that MP@H-MnO2-Dox-Col can increase the Dox effect with low cardiotoxicity based on multi-functions of effective penetration in tumor tissue, alleviating hypoxia in TME, pH sensitive drug release as well as targeted delivery of Dox. Conclusions This multifunctional biomimetic nanodelivery system exhibited antitumor efficacy in vivo and in vitro, thus having potential for the treatment of breast cancer.

Nanocatalysts for modulating antitumor immunity: fabrication, mechanisms and applications

“…Therefore, collagenase can be used to hydrolyze peptide bonds in collagen, thereby disrupting the dense ECM structure. 388 For example, Chen et al loaded collagenase onto mesoporous silica nanoparticles and degraded type I collagen fibers in ECMs, enhancing the penetration of nanomaterials into tumors. 389 Schroeder et al encapsulated collagenase in liposomes, improving drug delivery to the pancreas for pancreatic ductal adenocarcinoma.…”

Nanozymes with biomimetically designed properties for cancer treatment

“…Additionally, incorporating doxorubicin (DOX) into this treatment protocol markedly enhances its antitumor efficacy in vivo . Furthermore, Li et al 175 engineered an innovative nanosystem, H-MnO 2 -DOX-Col NPs, using mesoporous manganese dioxide (H-MnO 2 ) as a base, encapsulating DOX within its core, and coating the surface with collagenase (Col) (Fig. 13B).…”

Advances in cell membrane-based biomimetic nanodelivery systems for natural products

“…The principle of hypotonic lysis is that cells will swell and rupture under low osmotic pressure to release the contents, which is widely used in the extraction of erythrocyte membrane (Feng et al., 2022 ; Xu et al., 2023a , 2023b ). Repeated freeze-thawing involves freezing cells at low temperatures and thawing them repeatedly at room temperature to remove the contents (Ji et al., 2023 ; Li et al., 2023b ). However, freezing and thawing can potentially cause damage such as reduced protein activity.…”