Efficacy and safety of traditional Chinese medicine decoction combined with chemotherapy in the treatment of advanced colorectal cancer: A protocol of a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer has become a major chronic and difficult disease endangering human health. After thousands of years of precipitation, traditional Chinese medicine in China is now also being applied in clinical treatment, with its unique advantages in the treatment of cancer. However, the efficacy of traditional Chinese medicine in the treatment of advanced colorectal cancer still cannot reach consensus in the world. Therefore, the aim of this study was to provide a scheme to evaluate the efficacy and safety of traditional Chinese medicine decoction in the treatment of advanced colorectal cancer, thus providing clinical decision-making. METHODS AND ANALYSIS: The systematic review and meta-analysis will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The following 8databases will be searched: China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wan Fang Data, the Chinese Science and Technology Periodical Database (VIP), PubMed, Cochrane Library, Embase, and Web of Science. Relevant data will be performed by Revman 5.3 software provided (Cochrane Collaboration) and Stata 14.0 statistical software. RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. INPLASY REGISTRATION NUMBER: INPLASY202080102.

Enhancing siRNA-based cancer therapy using a new pH-responsive activatable cell-penetrating peptide-modified liposomal system.

As a potent therapeutic agent, small interfering RNA (siRNA) has been exploited to silence critical genes involved in tumor initiation and progression. However, development of a desirable delivery system is required to overcome the unfavorable properties of siRNA such as its high degradability, molecular size, and negative charge to help increase its accumulation in tumor tissues and promote efficient cellular uptake and endosomal/lysosomal escape of the nucleic acids. In this study, we developed a new activatable cell-penetrating peptide (ACPP) that is responsive to an acidic tumor microenvironment, which was then used to modify the surfaces of siRNA-loaded liposomes. The ACPP is composed of a cell-penetrating peptide (CPP), an acid-labile linker (hydrazone), and a polyanionic domain, including glutamic acid and histidine. In the systemic circulation (pH 7.4), the surface polycationic moieties of the CPP (polyarginine) are "shielded" by the intramolecular electrostatic interaction of the inhibitory domain. When exposed to a lower pH, a common property of solid tumors, the ACPP undergoes acid-catalyzed breakage at the hydrazone site, and the consequent protonation of histidine residues promotes detachment of the inhibitory peptide. Subsequently, the unshielded CPP would facilitate the cellular membrane penetration and efficient endosomal/lysosomal evasion of liposomal siRNA. A series of investigations demonstrated that once exposed to an acidic pH, the ACPP-modified liposomes showed elevated cellular uptake, downregulated expression of polo-like kinase 1, and augmented cell apoptosis. In addition, favorable siRNA avoidance of the endosome/lysosome was observed in both MCF-7 and A549 cells, followed by effective cytoplasmic release. In view of its acid sensitivity and therapeutic potency, this newly developed pH-responsive and ACPP-mediated liposome system represents a potential platform for siRNA-based cancer treatment.