Improving Antitumor Activity with N-Trimethyl Chitosan Entrapping Camptothecin in Colon Cancer and Lung Cancer

Abstract

Camptothecin (CPT) exerts very strong antitumor activities by suppressing the activity of DNA topoisomerase I, but its application is greatly limited owing to its low solubility and the instability of the active lactone form. To overcome this bottleneck, we prepared the novel camptothecin nanocolloids based on N-trimethyl chitosan (CPT-TMC) to efficiently administer CPT systemically. In this study, we investigated the antitumor activity of CPT-TMC against both colon cancer and lung cancer. In vitro cell experiments both CPT and CPT-TMC significantly inhibited the growth of CT26 cells and LL/2 cells, but no statistical difference was observed between CPT-TMC and CPT. In vivo studies, CPT-TMC more effectively inhibited tumor growth and prolonged survival time than CPT both in the CT26 colon carcinoma subcutaneous model and in the LL/2 Lewis lung carcinoma subcutaneous model. In addition, results of PCNA and CD31 immunohistochemical staining of tumor tissues also confirmed the improved antitumor effect of CPT-TMC. These findings suggest that N-trimethyl chitosan could increase the antitumor effect of CPT. Consequently, CPT delivery by N-trimethyl chitosan is a potential approach for effective treatment of cancer.

Association between expression of DNA mismatch repair genes and clinical features and prognosis of patients with radical resection of colon cancer

“…Surgical resection is the current major treatment for colon cancer. However, as tiny lesions may be overlooked during the surgery, the possibility of recurrence in patients with stage II/III colon cancers is approximately 20-50% (Clarizia et al, 2006;De Sousa E. Melo et al, 2013;Jin et al, 2014;Parnaby et al, 2015;Sun et al, 2015;Tan et al, 2015). DNA mismatch repair (MMR) proteins, such as hMLH1, hMSH2, hMSH6, and hPMS2, correct base mismatches that occur during DNA replication, and are therefore an important component in maintaining genomic stability (Erie and Weninger, 2014;Xu et al, 2015).…”

Current Advances in Chitosan Nanoparticles Based Oral Drug Delivery for Colorectal Cancer Treatment

“…Tumor growth and prolonged the survival time were efficiently suppressed by N-trimethyl chitosan nanocolloids compared with free camptothecin in the CT26 colon carcinoma subcutaneous model. [ 213 ] N,N,N-trimethyl chitosan chloride/poly (acrylic acid)/silver (TMC/PAA/Ag) nanocomposites - - PS= 30–65 nm HCT116 TMC/PAA/Ag (3%) had the highest cytotoxicity effect (the less cell viability %) on colon cancer line compared with TMC/PAA/Ag (2%) and TMC/PAA nanocomposites. [ 214 ] PLGA nanoparticles coated with folic acid-chitosan (αT-PCF-NPs) Alpha terpineol Folate receptor PS= 263.95 nm PDI= 25% ZP= +38.20 mV EE= 88.1% HT-29 αT-PCF-NPs had an inhibitory effect on HT-29 cells compared to HFF cells through pro-apoptotic effect and anti-apoptotic genes.…”