Perfluoroalkyl groups-containing polymeric micelles were constructed to transport oxygen, overcome the hypoxia of tumours and enhance photodynamic cancer therapy.

The drug resistance in cancer treatment with DOX is mainly related to the overexpression of drug efflux proteins, residing in the plasma and nuclear membranes. Delivering DOX into the mitochondria, lacking drug efflux proteins, is an interesting method to overcome DOX resistance. To solve the problem of positively charged triphenylphosphonium (TPP) for mitochondrial targeting in vivo, a charge reversal strategy was developed.Methods: An acidity triggered cleavable polyanion PEI-DMMA (PD) was coated on the surface of positively charged lipid-polymer hybrid nanoparticle (DOX-PLGA/CPT) to form DOX-PLGA/CPT/PD via electrostatic interaction. The mitochondrial localization and anticancer efficacy of DOX-PLGA/CPT/PD was evaluated both in vitro and in vivo.Results: The surface negative charge of DOX-PLGA/CPT/PD prevents from rapid clearance in the blood and improved the accumulation in tumor tissue through the enhanced permeability and retention (EPR) effect. The hydrolysis of amide bonds in PD in weakly acidic tumor tissue leads to the conversion of DOX-PLGA/CPT/PD to DOX-PLGA/CPT. The positive charge of DOX-PLGA/CPT enhances the interaction with tumor cells, promotes the uptake and improves DOX contents in tumor cells. Once endocytosed by tumor cells, the exposed TPP in nanomedicine results in effective mitochondrial localization of DOX-PLGA/CPT. Afterward, DOX can release from the nanomedicine in the mitochondria, target mtDNA, induce tumor cells apoptosis and overcome DOX resistance of MCF-7/ADR breast cancer.Conclusion: Tumor acidity triggered charge reversal of TPP-containing nanomedicine and activation of mitochondrial targeting is a simple and effective strategy for the delivery of DOX into the mitochondria of cancer cells and overcoming DOX resistance of MCF-7/ADR tumor both in vitro and in vivo, providing new insight in the design of nanomedicines for cancer chemotherapy.

Reliability engineering plays an important role in the design, manufacture, maintenance, and replacement of industrial products. Over the last few decades, accelerated degradation testing (ADT) has been largely utilized to shorten test durations, reduce the samples needed, and provide sufficient degradation data to ensure the effective reliability assessment of the concerned products. Meanwhile, performance degradation modeling has been recognized as an essential approach to help researchers and producers understand the health conditions of the deteriorating systems. However, the diversity in reliability tests, degradation models, and statistical analysis techniques has increased the difficulty in selecting appropriate reliability assessment methods in specific scenarios. Besides, there are no systematic reviews focused on modeling and analysis of performance degradation data. Therefore, this paper aims to (1) present ADT fundamentals, including the basic theory, ADT methods, accelerated stress variables, type of acceleration models, as well as ADT optimization, (2) comprehensively review current states and future challenges in degradation modeling, (3) discuss the problem of model mis-specification and compare different approaches for parameter estimation, (4) highlight future opportunities and possible directions deserving further research.

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