A facile strategy for fine-tuning the stability and drug release of stimuli-responsive cross-linked micellar nanoparticles towards precision drug delivery

Abstract

Precision drug delivery has great impact on the application of precision oncology for better patient care. Here we report a facile strategy for fine-tuning the stability, drug release and responsiveness of stimuli-responsive cross-linked nanoparticles towards precision drug delivery. A series of micellar nanoparticles with different levels of intramicellar disulfide crosslinkages could be conveniently produced with a mixed micelle approach. These micellar nanoparticles were all within a size range of 25–40 nm so that they could take full advantage of the enhanced permeability and retention (EPR) effect for tumor-targeted drug delivery. The properties of these nanoparticles such as critical micelle concentration (CMC), stability, drug release and responsiveness to reductive environment could be well correlated to the levels of crosslink (LOC). Compared to the micellar nanoparticles with a LOC at 0% that caused death of animals of two species (mouse and rat) due to the acute toxicity such as hemolysis, the nanoparticles at all other levels of crosslink were much safer to be administered into animals. The in vitro antitumor efficacy of micellar nanoparticles crosslinked at lower levels (20% & 50%) were much more effective than that of 100% crosslinked micellar nanoparticles in SKOV-3 ovarian cancer cells.

Optimization and Formulation of Nanostructured and Self-Assembled Caseinate Micelles for Enhanced Cytotoxic Effects of Paclitaxel on Breast Cancer Cells

“…Additionally, broad size distribution occurred due to casein reassembled nature but as the figure ( Figure 7 A) shows more than 90% of micelle intensity lies in the 200 nm particle size range, indicating the suitable particle size of our micelle. As long as the particles remain within the size range suitable for systemic administration and able to escape the leaky tumor vessels to reach the tumor, and prevent renal clearance and uptake by reticuloendothelial system, they could be used as smart nanocarriers, previously many studies in our lab [ 41 , 49 , 50 ] and also some other studies [ 51 , 52 , 53 ] supported that particles even though heterogeneous in size could be a fantastic nanocarrier system for efficient and tumor-targeted delivery of anti-cancer drugs and genetic materials.…”

Nano-drug System Based on Hierarchical Drug Release for Deep Localized/Systematic Cascade Tumor Therapy Stimulating Antitumor Immune Responses

“…Stability is one of the significant factors for therapeutic effects, and the encapsulation efficiency is considered as the key criterion to evaluate colloidal stability 34. In this study, the BV/PTX@Au@PDA/DOX was stored at 4 for a period of 0, 5, 10, and 15 days.…”

Telodendrimers: Promising Architectural Polymers for Drug Delivery

“…By mixing telodendrimers with and without cysteine moieties, they investigated the optimal level of cross-linking in relation to micelle properties, such as stability, drug release, and responsiveness to the reductive environment. It was reported that cross-linking levels of 20% and 50% were more effective antitumor formulations against in vivo SKOV-3 ovarian cancer cells [ 185 ].…”