<p>pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer</p>

Abstract

In this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(βamino ester) (PEOz-PLA-PBAE) triblock copolymers were synthesized and were conjugated with an antimalaria drug artesunate (ART), for inhibition of a colon cancer xenograft model. Methods: The as-prepared polymer prodrugs are tended to self-assemble into polymeric micelles in aqueous milieu, with PEOz segment as hydrophilic shell and PLA-PBAE segment as hydrophobic core. Results: The pH sensitivity of the as-prepared copolymers was confirmed by acid-base titration with pKb values around 6.5. The drug-conjugated polymer micelles showed high stability for at least 96 h in PBS and 37°C, respectively. The as-prepared copolymer prodrugs showed high drug loading content, with 9.57%±1.24% of drug loading for PEOz-PLA-PBAE-ART4. The conjugated ART could be released in a sustained and pH-dependent manner, with 92% of released drug at pH 6.0 and 57% of drug released at pH 7.4, respectively. In addition, in vitro experiments showed higher inhibitory effect of the prodrugs on rodent CT-26 cells than that of free ART. Animal studies also demonstrated the enhanced inhibitory efficacy of PEOz-PLA-PBAE-ART2 micelles on the growth of rodent xenograft tumor. Conclusion: The pH-responsive artesunate polymer prodrugs are promising candidates for colon cancer adjuvant therapy.

<p>Synergistic Combination Chemotherapy of Lung Cancer: Cisplatin and Doxorubicin Conjugated Prodrug Loaded, Glutathione and pH Sensitive Nanocarriers</p>

“…[37][38][39] pH sensitive prodrugs have also been utilized to deliver more drugs to the acidic tumor site. [40][41][42] This research combined the GSH and pH sensitive property to one system. The GSH sensitive property of the nanocarriers was evaluated in PBS with or without the presence of GSH to resemble the difference of cellular environment between tumor cells and normal cells.…”

Artemisinin-Type Drugs in Tumor Cell Death: Mechanisms, Combination Treatment with Biologics and Nanoparticle Delivery

“…For example, the pH-responsive DHA-GO-TF and TF-8arm-PEG-DHA delivery systems both showed higher solubility, enhanced tumor delivery specificity, minimal side-effects, and superior tumor growth restrained ability in vivo [184,185]. Third, the release of metal ions by polymer-based nanoparticles was shown to enhance ART or ART derivative-induced tumor inhibition [187][188][189].…”

Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery

“…Efficiently decrease VEGF expression level by about 54.4% and inhibit the formation of intratumoral microvessels at the tumor tissue [16] miR-204-5p inhibitor Apo A-I-mediated active targeting Human ovarian cancer In vitro and in vivo Silence the expression of the oncogene miR-204-5p at tumor sites, inhibit tumor growth, induce 50% reduction in tumor weight [17] Pharmaceutics 2021, 13, 1151 Inhibit original tumor growth, the tumor volumes in micelle group are 1.34-fold smaller than ART group in the 21st day post-treatment [18] S-nitrosoglutathione and doxorubicin ROS and GSH-sensitive targeting Human liver cancer In vitro…”

“…Therefore, it is desirable to design an ART depot with sustained release and targeted delivery properties. Hao et al prepared a micelle composed of pH-sensitive PEOz as hydrophilic corona and polylactide/PBAE conjugation with ART as the hydrophobic core [ 18 ]. The outside copolymer exhibited proton sponge properties at a pH below its pKb (~6.5) owing to the presence of amine groups, which resulted in its pH sensitivity [ 98 ].…”