Abstract
Natural prodrugs derived from different natural origins (e.g., medicinal plants, microbes, animals) have a long history in traditional medicine. They exhibit a broad range of pharmacological activities, including anticancer effects in vitro and in vivo. They have potential as safe, cost-effective treatments with few side effects, but are lacking in solubility, bioavailability, specific targeting and have short half-lives. These are barriers to clinical application. Nanomedicine has the potential to offer solutions to circumvent these limitations and allow the use of natural pro-drugs in cancer therapy. Mesoporous silica nanoparticles (MSNs) of various morphology have attracted considerable attention in the search for targeted drug delivery systems. MSNs are characterized by chemical stability, easy synthesis and functionalization, large surface area, tunable pore sizes and volumes, good biocompatibility, controlled drug release under different conditions, and high drug-loading capacity, enabling multifunctional purposes. In vivo pre-clinical evaluations, a significant majority of results indicate the safety profile of MSNs if they are synthesized in an optimized way. Here, we present an overview of synthesis methods, possible surface functionalization, cellular uptake, biodistribution, toxicity, loading strategies, delivery designs with controlled release, and cancer targeting and discuss the future of anticancer nanotechnology-based natural prodrug delivery systems.
Highlights
In 2001, Vallet-Regi et al [1] introduced a mesoporous silica material called Mobil crystalline materials (MCMs)-41 that can be used as a drug carrier
The first clinical trial in humans was conducted with oral delivery of fenofibrate formulation based on the ordered mesoporous silica [33]
Yinxue et al [199] investigated myricetin prodrug (Myr)-loaded mesoporous silica nanoparticles (MSNs) combined with multidrug resistance protein (MRP-1) siRNA and the surface modified with folic acid to treat non-small cell lung cancer (NSCLC)
Summary
In 2001, Vallet-Regi et al [1] introduced a mesoporous silica material called MCM-41 that can be used as a drug carrier. An important advantage of DDS-based MSNs is that the amorphous forms of silica and silicates are generally recognized as safe materials for use as oral delivery ingredients (up to 1500 mg per day) according to the US Food and Drug Administration and the European Food Safety Authority [27]. The first clinical trial in humans was conducted with oral delivery of fenofibrate formulation based on the ordered mesoporous silica [33] Despite these promising results for nanotechnology application in building DDSs, most research for targeted cancer therapy has been focused on drugs and therapeutic molecules of a synthetic nature. This review may help researchers accelerate research and development of this important field of nanomedicine and, clinical applications
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