Novel CD44-targeting and pH/redox-dual-stimuli-responsive core–shell nanoparticles loading triptolide combats breast cancer growth and lung metastasis

Abstract

Background The toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited the clinical application. Thus, we fabricated a CD44-targeting and tumor microenvironment pH/redox-sensitive nanosystem composed of hyaluronic acid-vitamin E succinate and poly (β-amino esters) (PBAEss) polymers to enhance the TPL-mediated suppression of breast cancer proliferation and lung metastasis. Results The generated TPL nanoparticles (NPs) had high drug loading efficiency (94.93% ± 2.1%) and a desirable average size (191 nm). Mediated by the PBAEss core, TPL/NPs displayed a pH/redox-dual-stimuli-responsive drug release profile in vitro. Based on the hyaluronic acid coating, TPL/NPs exhibited selective tumor cellular uptake and high tumor tissue accumulation capacity by targeting CD44. Consequently, TPL/NPs induced higher suppression of cell proliferation, blockage of proapoptotic and cell cycle activities, and strong inhibition of cell migration and invasion than that induced by free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and blocking lung metastasis with decreased systemic toxicity in a 4T1 breast cancer mouse model at an equivalent or lower TPL dosage compared with that of free TPL. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis and suppressed expression of matrix metalloproteinases, which contributed to inhibiting tumor growth and pulmonary metastasis. Conclusion Collectively, our results demonstrate that TPL/NPs, which combine tumor active targeting and pH/redox-responsive drug release with proapoptotic and antimobility effects, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity. Graphic Abstract

Activatable NIR-II organic fluorescent probes for bioimaging

“…Responsive probes associated with a single molecule are easy to emit “false positive” signals, while probes activated by two or more pathological changes make the imaging precise and become more attractive ( Table 1 and Figure 16 - 18 ) 102 , 134 - 141 . An activatable NIR-II nanoprobe HISSNPs was developed, which responds to dual-pathological-parameter to control the fluorescence condition for tumor imaging.…”

Single and Multiple Stimuli-Responsive Polymer Particles for Controlled Drug Delivery

“…[ [116][117][118][119][120][121][122] PEG-PEI-GEM polyethylenimine-graft-poly(ethylene glycol)gemcitabine pH Light…”

“…Because redox reactions and differences in pH occur naturally in the body, these two stimuli are very appealing for drug delivery applications [133]. These types of polymers have been created for a myriad of applications, such as enhancing drug delivery and tumor cell uptake, creating a faster drug release rate within the cytoplasm and nucleus, and further stabilizing the stability of nanoparticles in vivo [116,133].…”

Delivery of triptolide: a combination of traditional Chinese medicine and nanomedicine

“…In order to improve the tumor delivery rate and anti-metastatic effect of chemotherapy, Zhang et al designed a CD44-targeting and pH/redox-sensitive nanosystem, which can actively target CD44 overexpressed on the cell surface through hyaluronic acid and release the drug in response to the tumor microenvironment, improving the antitumor effect. At the same time, lung metastasis of tumor was inhibited [ 142 ]. The results in vitro and in vivo indicated that the preparation had good effect on promoting tumor cell apoptosis and anti-tumor metastasis.…”