Meta-Analysis of Efficacy of Chemotherapy Delivered by Mesoporous Silica Nanoparticles to Tumor-Bearing Mice.

Abstract

Nanomedicines have played an important role in the management of cancer patients with PEGylated liposomal doxorubicin (e.g., Doxil) and nab-paclitaxel (Abraxane) being two examples that have been commercially successful. However, the number of patients benefitting from these therapies is small compared with the potential impact. While off-site toxicities have been reduced, long term survival has not been realized. Thus, there continues to be a need for improved therapies and nanomedicine (delivery of drugs using nanoparticle carriers) that provide advantages over the delivery of free drug. Mesoporous silica nanoparticles (MSNs) are a unique class of nanomedicine that offers high loading capacity, the ability of targeting specificity, potential for stimulated drug release and are considered generally safe and non-toxic. This paper provides a comprehensive analysis of 166 published studies in which MSNs were evaluated in vivo and tumor response was reported. Eleven studies with liposomal doxorubicin and 3 studies with Abraxane are also included in the analysis. The MSN formulations exhibit a wide range of size, charge, drug loading and drug release. The tumor inhibition ratio (TIR) of some MSN formulations compared favorably to the FDA approved nanomedicines. However, TIR reached at least 99% in only 14 MSN formulations reported. On average, targeted MSNs and MSNs with combined therapy (multiple drugs, or drugs combined with thermal therapy) performed best. Survival was reported in 14 MSN studies. The reported increased life survival (ILS) tended to be longer for liposomal doxorubicin and Abraxane than for the MSN formulations. The paper also provides an overview of MSN synthesis strategies and compares the development timeline of MSNs to that of Doxil and Abraxane, discussing the barriers to commercialization. Finally, the paper provides recommendations to advance the development and commercialization of MSNs for cancer therapy.