Unique Advantages of Dendrimers-Structured Mesoporous Silica Nanoparticles over Traditional Hollow Ones in Delivering Bcl2-Functional Converting Peptide for Multidrug Resistant Cancer Treatment.

Abstract

Innovative silica nanomaterials have made the significant advancements in curative therapy against cancers with multidrug resistance (MDR). The study on different-nanostructured mesoporous silica nanoparticles (MSNs) with discrepant pore sizes affecting biomacromolecules in resisting cancer MDR hasn't been reported yet. In this study, a systematic comparison of 6nm-pore sized hollow-structured MSNs (HMSNs) and 10nm-pore sized dendrimers-structured MSNs (LMSNs) for delivering Bcl-2-functional converting peptide (N9) or doxorubicin (DOX) to overcome cancer MDR is comprehensively carried out both in in vitro and in vivo resistant tumor models. The results show that both LMSNs and HMSNs exert no significant difference in delivering DOX to treat drug-resistant cancers. However, compared with N9@HMSNs, N9@LMSNs display the increased loading efficiency, the improved cell-penetrative capability, the higher cancer cell apoptosis effect, the enhanced tumor accumulation and retention efficiency, and the final elevated tumor inhibition efficiency. Unexpectedly, naked LMSNs without surface modification especially at high dosage produce relatively more serious toxicity than HMSNs whatever in cells, zebrafish embryo or mice models. Collectively, the data provide the sufficient theoretical evidence that LMSNs might be a better choice for delivering biomacromolecules to treat resistant cancers after appropriate surface functionalization such as with PEGylation to weaken its intrinsic toxicity.