<p>Acid-responsive nanoparticles as a novel oxidative stress-inducing anticancer therapeutic agent for colon cancer</p>

Abstract

Nanoparticles can efficiently carry and deliver anticancer agents to tumor sites. Mounting evidence indicates that many types of cancer cells, including colon cancer, have a weakly acidic microenvironment and increased levels of reactive oxygen species. The construction of nano drug delivery vehicles "activatable" in response to the tumor microenvironment is a new antitumor therapeutic strategy. Methods: Cinnamaldehyde (CA) was designed to link directly with dextran to form a polymer through an acid cleavable acetal bond. Herein, a novel pH-sensitive drug delivery system was constructed with co-encapsulated 10-hydroxy camptothecin (HCPT). Dynamic light scattering (DLS) analysis, transmission electron microscopy (TEM) analysis, and release kinetics analysis of HCPT-CA-loaded nanoparticles (PCH) were conducted to investigate the physical and chemical properties. The cellular uptake signatures of the nanoparticles were observed by confocal microscopy and flow cytometry. Cell viability, cell scratch assay, apoptosis assay, and colony formation assay were performed to examine the potent antiproliferative and apoptotic effects of the PCH. The antitumor mechanism of the treatment with PCH was evaluated by Western blotting, flow cytometry, and TEM analysis. The pharmacokinetics of PCH were examined in healthy Sprague Dawley rats within 6 hours after sublingual vein injection. We lastly examined the biodistribution and the in vivo anticancer activity of PCH using the xenograft mouse models of HCT116 cells. Results: Both HCPT and CA were quickly released by PCH in an acidic microenvironment. PCH not only induced cancer cell death through the generation of intracellular reactive oxygen species in vitro but also facilitated the drug uptake, effectively prolonged drug circulation, and increased accumulation of drug in tumor sites. More attractively, PCH exhibited excellent therapeutic performance and better in vivo systemic safety. Conclusion: Overall, PCH not only utilized the tumor microenvironment to control drug release, improve drug pharmacokinetics, and passively target the drug to the tumor tissue, but also exerted a synergistic anticancer effect. The acid-responsive PCH has enormous potential as a novel anticancer therapeutic strategy.

pH-Responsive Polymer Nanomaterials for Tumor Therapy

“…Acetal/ketal bonds are also widely used in pH-responsive polymer nano-DDSs (NDDSs). Zhao et al ( 91 ) polymerized cinnamaldehyde (CA) directly with glucose through acid-unstable acetal bonds and encapsulated 10-hydroxy camptothecin (HCPT), and then, synthesized a novel type of pH-responsive DDS comprising HCPT–CA-loaded NPs (PCH). In an acidic environment, both HCPT and CA could be rapidly released by PCH.…”

Smart Responsive Nanoformulation for Targeted Delivery of Active Compounds From Traditional Chinese Medicine

“…The acetal linkage dissociated in the acidic environment, and cinnamaldehyde and maltodextrin could return to their native states. Zhao et al ( 2019a ) also used acetal linkages to couple cinnamaldehyde and dextran in 10-hydroxy camptothecin-cinnamaldehyde nanoparticles. The acetal linkage of cinnamaldehyde was hydrolyzed from dextran at an acidic pH, which broke the nanoparticles into water-soluble fragments, and resulted in rapid dissociation.…”

Nanovectors Design for Theranostic Applications in Colorectal Cancer

“…These particles were able to release the drugs in a pH-dependent fashion, to cause ER-stress, selective tumor cells apoptosis by ROSs production and prevent colony formation and wound healing of tumor cell lines in vitro . Furthermore, the encapsulated drug showed increased plasmatic half-life in vivo and decrease renal toxicity of the drugs, increasing tumor accumulation and significantly reducing tumor growth [60].…”