Dual Hypoxia-Targeting RNAi Nanomedicine for Precision Cancer Therapy

Abstract

As a hallmark of solid tumors, hypoxia promotes tumor growth, metastasis, and therapeutic resistance by regulating the expression of hypoxia-related genes. Hypoxia also represents a tumor-specific stimulus that has been exploited for the development of bioreductive prodrugs and advanced drug delivery systems. Cell division cycle 20 (CDC20) functions as an oncogene in tumorigenesis, and we demonstrated the significant upregulation of CDC20 mRNA in the tumor vs paratumor tissues of breast cancer patients and its positive correlation with tumor hypoxia. Herein, a hypoxia-responsive nanoparticle (HRNP) was developed by self-assembly of the 2-nitroimidazole-modified polypeptide and cationic lipid-like compound for delivery of siRNA to specifically target CDC20, a hypoxia-related protumorigenic gene, in breast cancer therapy. The delivery of siCDC20 by HRNPs sufficiently silenced the expression of CDC20 and exhibited potent antitumor efficacy. We expect that this strategy of targeting hypoxia-correlated protumorigenic genes by hypoxia-responsive RNAi nanoparticles may provide a promising approach in cancer therapy.

Recent Developments on Semiconducting Polymer Nanoparticles as Smart Photo-Therapeutic Agents for Cancer Treatments—A Review

“…The degree of intracellular O 2 level or hypoxia has been considered as an early indicator of cancers, and many efforts have been made to develop responsive drug delivery systems and SPN based NPs for targeting such hypoxic environments in cancers [ 96 , 97 , 98 , 99 , 100 , 101 , 102 ]. PDT agents can typically make use of such low oxygen environments to generate ROS, which in turn effectively eradicate cancerous tissues and cells.…”

Recent advances in peptide-based nanomaterials for targeting hypoxia

“…The delivery nanosystem showed prolonged blood circulation, high tumor accumulation, efficient CDC20 silencing, and high potent antitumor efficacy. 36 Hypoxia-responsive polypeptides based on nitrobenzyl alcohol derivatives (NADs) are commonly found in the literature. One example of these, investigated by Park and co-workers, involved preparing hypoxia-responsive polymeric micelles formed by an amphiphilic block copolymer poly(ethylene glycol)-poly(ε-(4-nitro)benzyloxycarbonyl-L-lysine),…”

Design, Bioanalytical, and Biomedical Applications of Aptamer-Based Hydrogels

“…Compared with viral vectors, non-viral vectors are safer and more desirable. Therefore, the development of safe non-viral vectors is highly desirable (97,149,152,153).…”