Bioreducible nanocapsules for folic acid-assisted targeting and effective tumor-specific chemotherapy

Abstract

Introduction Increasing demands in precise control over delivery and functionalization of therapeutic agents for tumor-specific chemotherapy have led to a rapid development in nanocarriers. Herein, we report a nanocapsule (NC) system for tumor-oriented drug delivery and effective tumor therapy. Materials and methods Functionalized hyaluronan is utilized to build up the NC shells, in which bioreduction cleavable sites, targeting ligand folic acid (FA), and zwitterionic tentacles are integrated. Results The hollow NCs obtained (~50 nm in diameter) showed well-defined spherical shell structures with a shell thickness of ~8 nm. These specially designed NCs (doxorubicin [DOX]/FA-Z-NCs) with high drug encapsulation content exhibited good biocompatibility in vitro and fast intracellular drug release behavior mediated by intracellular glutathione. Conclusion Cellular uptake tests demonstrated rapid uptake of these functionalized NCs and effective escape from endosomes. Antitumor efficacy of the DOX/FA-Z-NCs was confirmed by the significant tumor growth inhibition effect as well as greatly reduced side effects, in contrast with those of the free drug DOX hydrochloride.

Enhancing the in vitro and in vivo activity of itraconazole against breast cancer using miltefosine-modified lipid nanocapsules

“…Tumor cell proliferation and treatment efficacy can be assessed by the Ki-67 proliferative protein expression determined by immunohistochemical staining of the tumor (Dowsett et al., 2011 ; Yi et al., 2018 ). The tumor section of untreated mice showed the maximum Ki-67 expression ( Figure 6(C) ).…”

“…The anti-proliferative activity of test formulations was determined by tumor immunohistochemical staining of the Ki-67 proliferating protein in formalin-fixed, paraffin-embedded specimens (Yi et al., 2018 ). Briefly, 4 μm-thick tumor tissue sections were dried, deparaffinized, and rehydrated following standard procedures.…”

Crosslinked polymer nanocapsules for therapeutic, diagnostic, and theranostic applications

“…Their biodegradability is also preferred to allow eventual elimination and to minimize their long‐term side effects. Accordingly, biopolymers with intrinsic degradability, such as alginate (Nguyen et al, 2015), chitosan (Chen, Wang, et al, 2014; Yin et al, 2010), hyaluronic acid (Yi, Ma, Kang, & Gu, 2018), and starch (Baier et al, 2012), have been employed as the base polymers of CPNCs. A broad variety of CPNCs derived from synthetic polymers have also been studied, and in principle, their non‐cleavable segments should have a molecular weight (MW) less than 40 kDa to facilitate renal clearance (Tong & Cheng, 2007).…”

“…Furthermore, dual redox‐responsiveness to higher concentrations of both reactive oxygen species (ROS; an oxidizing agent) and glutathione (a reducing agent) in cancer cells resulted in triggered release of DOX and an excellent antitumor effect. Using FA as tumor‐targeting moiety, Yi et al demonstrated that hyaluronic acid‐based, DOX‐encapsulated CPNCs with FA‐terminated zwitterionic tentacles exhibited both a higher cytotoxicity, more efficient in vitro cellular uptake by 4 T1 cells, and more significant antitumor efficacy toward tumor‐bearing BALB/c mouse, as compared to the control CPNCs without FA modification (Yi et al, 2018).…”

<p>Static DNA Nanostructures For Cancer Theranostics: Recent Progress In Design And Applications</p>

“…These redox/pH dual stimuli-responsive nanohydrogels make promising candidates for delivering anti-cancer drugs because of their biocompatibility, adequate drug loading capacity, biodegradability, controlled yet fast drug release potential (Figure 8B). 160 Moreover, bioreducible nanohydrogels-like nanocapsules (NCs) were reported to actively target cancer cells coated with folic acid 27Figure 8DNA nanoswitch systems as cancer theranostics.…”