Abu-Serie Marwa M, El-Rashidy Fatma H
Medical Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, City for Scientific Research and Technology Applications (SRTA-City), New Borg El Arab, Alexandria. Egypt.
Biochemistry Department, Faculty of Science, Alexandria University, Alexandria. Egypt.
Recent Pat Anticancer Drug Discov. 2017;12(3):260-271. doi: 10.2174/1574892812666170424144925.
Different strategies against colon cancer are accompanied by treatment failure, because of drug toxicity toward normal cells and cancer stem cells (CSCs) resistance. However, previous patent evaluated liposome that encapsulated inhibitor of CSCs' aldehyde dehydrogenase (ALDH)1; disulfiram, for targeting breast CSCs. Liposome has disadvantages due to its hydrophobicity.
Designing hydrophilic nanoparticles has selectivity to release disulfiram in CC cells rather than in normal colonocytes based on variation in microenvironment between normal and cancer cells.
Disulfiram was nanoformulated by its loading into cationic chitosan and coating with anionic albumin. Their selectivity and targeting were investigated using murine and human colon cancer cells compared to normal mice colon cells.
Zeta potential of the coated nanoparticles confirmed that albumin-layering confers negative charge (-10.3mv) for disulfiram-loaded chitosan nanoparticles (52.9mv). In slightly acidic medium of tumor, the ionic bond between albumin and chitosan hydrolyzed then the positive charge was reversed (47.6mv). Thus coated nanoparticles showed higher sustain release for disulfiram in tumor microenvironment than neutral pH and their uptake was higher in cancer cells than normal cells. This interpreted the highest selectivity of coated nanoparticles for enhancing apoptosis and eliminating CSCs in cancer cells.
These patented coated nanoparticles were the most effective and selective for eradicating colon CSCs without insulting normal stem cells in comparison with disulfiram which was toxic to both normal and CSCs. This novel study that used charge switchable (hydrophilic) nanoparticles for targeting colon CSCs may represent a basis for future in vivo studies.
由于药物对正常细胞的毒性以及癌症干细胞（CSCs）的耐药性，针对结肠癌的不同治疗策略都伴随着治疗失败。然而，先前的专利评估了包裹癌症干细胞醛脱氢酶（ALDH）1抑制剂双硫仑的脂质体，用于靶向乳腺癌症干细胞。脂质体因其疏水性存在缺点。
基于正常细胞与癌细胞微环境的差异，设计对双硫仑在结肠癌细胞中而非正常结肠细胞中有选择性释放的亲水性纳米颗粒。
通过将双硫仑负载于阳离子壳聚糖并包覆阴离子白蛋白来制备其纳米制剂。与正常小鼠结肠细胞相比，使用小鼠和人结肠癌细胞研究其选择性和靶向性。
包覆纳米颗粒的ζ电位证实，白蛋白层赋予负载双硫仑的壳聚糖纳米颗粒（52.9mv）负电荷（-10.3mv）。在肿瘤的微酸性介质中，白蛋白与壳聚糖之间的离子键水解，然后正电荷反转（47.6mv）。因此，包覆纳米颗粒在肿瘤微环境中对双硫仑的缓释能力高于中性pH环境，且其在癌细胞中的摄取高于正常细胞。这解释了包覆纳米颗粒在增强癌细胞凋亡和消除癌症干细胞方面具有最高的选择性。
与对正常干细胞和癌症干细胞均有毒性的双硫仑相比，这些获得专利的包覆纳米颗粒在根除结肠癌症干细胞方面最有效且具有选择性，不会损害正常干细胞。这项使用电荷可切换（亲水性）纳米颗粒靶向结肠癌症干细胞的新研究可能为未来的体内研究奠定基础。
