<p>Enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery</p>

Abstract

Background: Drug delivery systems (DDS) capable of targeting both cell and organelle levels are highly desirable for effective cancer therapy. In this study, we developed a novel enzyme-responsive, multistage-targeted anticancer DDS based on mesoporous silica nanoparticles (MSNs), which possessed both CD44-targeting and mitochondrial-targeting properties. Materials and methods: Triphenylphosphine (TPP), a mitochondria-targeting compound, was grafted onto the surface of MSNs firstly. Then, Doxorubicin (Dox) was encapsulated into the pore of MSNs, followed by capping with tumor-targeting molecules hyaluronic acid (HA) through electrostatic interactions to form the final product consist of Dox loaded, TPP attached, HA capped mesoporous silica nanoparticles (MSN-DPH). Results: Our results suggested that MSN-DPH was preferentially taken up by cancer cells via CD44 receptor-mediated endocytosis. Moreover, MSN-DPH mainly accumulated in mitochondria owing to the mitochondrial-targeting ability of TPP. Degradation of HA by overexpressed HAase facilitated the release of Dox in cancer cells. Thus, MSN-DPH efficiently killed the cancer cells while exhibited much lower cytotoxicity to normal cells. Conclusion: This study demonstrates a promising multistage-targeted DDS for cancer chemotherapy.

Tumor Microenvironment-Stimuli Responsive Nanoparticles for Anticancer Therapy

“…The DOX-loaded final nanoparticle showed toxicity to stomach cancer MGC-803 cells. A live/dead assay was conducted to understand more about the cytotoxicity of the nanoparticles (Figure 4) (Naz et al, 2019).…”

“…(B) Live/dead images of MGC-803 cells incubated with MSN and MSN-DPH nanoparticles. Reprinted with permission fromNaz et al (2019). This work is published and licensed by Dove Medical Press Limited and incorporate the Creative Commons Attribution-Non-Commercial (unported, v3.0) License (http:// creativecommons.org/licenses/by-nc/3.0/).…”

Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy

“…Based on mesoporous silica nanoparticles (MSNs), a novel enzyme-responsive, multistage-targeted anti-cancer drug delivery system which possessed both CD44-targeting and mitochondrial-targeting properties was developed by Naz and colleagues [143]. First, TPP was attached to the surface of the MSNs, and Dox was then encapsulated into the pore of the MSNs followed by its capping with tumour-targeting molecules of hyaluronic acid (HA).…”

“…The final product consists of Dox-loaded, TPP-attached, HA-capped mesoporous silica nanoparticles (MSN-DPH). MSN-DPH, preferentially taken up by cancer cells via CD44 receptor-mediated endocytosis, primarily accumulated in mitochondria and efficiently killed cancer cells while exhibiting much lower cytotoxicity to normal cells [143]. In addition, a novel delivery platform based on tetrahedral DNA nanostructures (TDNs) that enable mitochondrial import of Dox for cancer therapy was designed by Yan and colleagues.…”

Overcoming Hurdles in Nanoparticle Clinical Translation: The Influence of Experimental Design and Surface Modification

“…However, just as in other mechanisms of payload release, cancer is the most frequently researched disease state. One study used mesoporous silica nanoparticles encapsulating doxorubicin with triphenylphosphine (TPP) and hyaluronic acid (HA) grafted to the surface [93], not only demonstrating uptake by cancer cells via CD44 receptor-medicated endocytosis but also release of doxorubicin in response to HAase cleavage, ultimately decreasing cell viability to 34% [93]. This study demonstrates how effective enzyme responsive payload release can be.…”