Phosphatidylserine targeting peptide-functionalized pH sensitive mixed micelles for enhanced anti-tumor drug delivery
Drug delivery; pH-sensitive mixed micelles; Phosphatidylserine; Targeted peptide
In recent decades, targeted drug delivery systems (TDDS) have been widely used as an ideal method of improving therapeutic effects and reducing systemic side effects of chemotherapeutic agents. Historically, a handful of methods have been developed to further improve the targeting ability of delivery systems. Thus, in this study, two methods, taking advantage of tumor characteristics, were used for the creation of a multi-targeted delivery system. The first was the fabrication of pH-sensitive micelles, lending the ability to increase drug release by exploiting the acidic tumor environment. The second method was through utilization of the surface-exposed phosphatidylserine (PS) of tumors, which is normally found in the inner leaflet in healthy cells. Using PS as a target site, PS binding peptide (PSBP-6) was conjugated to pH-sensitive mixed micelles, (consisting of poly (ethylene glycol)-b-poly (D, L-lactide) (PEG-PDLLA) and poly (ethylene glycol)-b-poly (L-histidine) (PEG-PHIS)). After successful preparation of micelles, paclitaxel (PTX), a common chemotherapeutic agent, was selected to measure drug loading capacity and encapsulation efficiency, showing 7.9% and 83.5%, respectively. The in vitro release of PTX from mixed micelles at pH 5.0, 6.5, and 7.4 was 78.1, 56.8, and 51.4%, respectively, indicating acid-triggered drug release. The PSBP-6-modified, mixed micelles exhibited significantly enhanced in vitro cytotoxicity and demonstrated more efficient cellular uptake compared to unmodified mixed micelles in the HeLa cell line. Moreover, pharmacokinetic, in vivo biodistribution, and fluorescence imaging studies showed that PSBP-6-PEG-PDLLA/PEG-PHIS mixed micelles provide prolonged time in blood circulation and enhanced tumor accumulation. These results suggest that the use of PS as a novel targeting site is advantageous, and that these new multi-targeted mixed micelles show great potential for realization of broad prospects in the targeted treatment of tumors for chemotherapeutic delivery.
Guan Siyu; Zhang Qianqian; Bao Jianwei; Duan Tijie; Hu Rongfeng; Czech Tori; Tang Jihui
European Journal of Pharmaceutics and Biopharmaceutics: Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik e.V
2019
2019-12-30
Journal Article
<a href="http://doi.org/10.1016/j.ejpb.2019.12.012" target="_blank" rel="noreferrer noopener">10.1016/j.ejpb.2019.12.012</a>
PMID: 31899369
Recognition Sites for Cancer-Targeting Durg Delivery Systems
Nanoparticles; tumor; ligand; Recognition sites; targeted drug delivery system
BACKGROUND: Target-homing drug delivery systems are now gaining significant traction for use as novel therapeutic approaches in antitumor targeting for cancer therapy. Numerous targeted drug delivery systems have been designed to improve the targeting effects because these systems can display a range of favorable properties. Thus, providing suitable characteristics for clinical applicability of anticancer drugs, such as increasing the solubility, and improving the drug distribution at target sites. The majority of these targeting systems are designed with respect to differences between cancerous and normal tissues, for instance, the low pH of tumor tissues or overexpressed receptors on tumor cell membranes. Because of the growing number of targeting possibilities, it is important to know the tumor-specific recognition strategies for designing novel, targeted, drug delivery systems. Herein, we will identify and summarize literature pertaining to various recognition sites for optimizing the design of targeted drug delivery systems to augment current chemotherapeutic approaches. OBJECTIVE: This review focuses on identification of the recognition sites for developing targeted drug delivery systems for use in cancer therapeutics. METHOD: We have reviewed and compiled cancer-specific recognition sites and their abnormal characteristics within tumor tissues (low pH, high glutathione, targetable receptors, etc.), tumor cells (receptor overexpression or tumor cell membrane changes) and tumor cell organelles (nuclear and endoplasmic reticular dysregulation) utilizing existing scientific literature. Moreover, we have highlighted the design of some targeted drug delivery systems that can be used as homing tools for these recognition sites. RESULTS AND CONCLUSION: Targeted drug delivery systems are a promising therapeutic approach for tumor chemotherapy. Additional research focused on finding novel recognition sites, and subsequent development of targeting moieties for use with drug delivery systems will aid in the evaluation and clinical application of new and improved chemotherapeutics.
Guan Siyu; Zhang Qianqian; Bao Jianwei; Hu Rongfeng; Czech Tori; Tang Jihui
Current Drug Metabolism
2019
2019-10-03
Journal Article
<a href="http://doi.org/10.2174/1389200220666191003161114" target="_blank" rel="noreferrer noopener">10.2174/1389200220666191003161114</a>
PMID: 31580248