Injectable and Self-Healing Thermosensitive Magnetic Hydrogel for Asynchronous Control Release of Doxorubicin and Docetaxel to Treat Triple-Negative Breast Cancer

Abstract

Integration of two or more drugs into a multiagent delivery system has been considered to have profound impact on both in vitro and in vivo cancer treatment due to their efficient synergistic effect. This study presents a cheap and simple chitosan hydrogel cross-linked with telechelic difunctional poly(ethylene glycol) (DF-PEG-DF) for synthesis of an injectable and self-healing thermosensitive dual-drug-loaded magnetic hydrogel (DDMH), which contains both doxorubicin (DOX) and docetaxel (DTX) for chemotherapy and iron oxide for magnetic hyperthermia induced stimuli responsive drug release. The as-prepared DDMH not only have good biocompatibility but also exhibit unique self-healing, injectable, asynchronous control release properties. Meanwhile, it shows an excellent magnetic field responsive heat-inducing property, which means that DDMH will produce a large amount of heat to control the surrounding temperature under the alternative magnetic field (AMF). A remarkably improved synergistic effect to triple negative breast cancer cell line is obtained by comparing the therapeutic effect of codelivery of DOX and DTX/PLGA nanoparticles (DTX/PLGA NPs) with DOX or DTX/PLGA NPs alone. In vivo results showed that DDMH exhibited significant higher antitumor efficacy of reducing tumor size compared to single drug-loaded hydrogel. Meanwhile, the AMF-trigger control release of drugs in codelivery system has a more efficient antitumor effect of cancer chemotherapy, indicating that DDMH was a promising multiagent codelivery system for synergistic chemotherapy in the cancer treatment field.

Injectable and Self-Healing Chitosan Hydrogel Based on Imine Bonds: Design and Therapeutic Applications

“…Recently, Xie et al designed a thermosensitive dual-drug-loaded magnetic GC/DF-PEG hydrogel (DDMH), as shown in Figure 8a [47]. This hydrogel encapsulated both DOX and docetaxel (DTX)-PLGA nanoparticles for chemotherapy.…”

“…Data presented the mean ± standard deviation of five mice. Reprinted with permission [47]. Copyright 2015, American Chemical Society.…”

Nanocomposite Polymer Scaffolds Responding under External Stimuli for Drug Delivery and Tissue Engineering Applications

“…In another work by Xie et al, injected crosslinked chitosan-PEG hydrogels loaded with IO NPs reduced tumors in mice thanks to a combination of drug release (DOX and docetaxel) and hyperthermia. [193] In this work, the authors used a bi-functional PEG as crosslinkers for chitosan hydrogel matrix and formed a self-healing thermoresponsive scaffold embedded with the two synergic drugs and the magnetic NPs. The nanocomposite hydrogel was shown to be biocompatible and provided a relevant magnetothermal transfer upon AMF.…”

Non-Platinum Metal Complexes as Potential Anti-Triple Negative Breast Cancer Agents

“…However, both cisplatin chemotherapies and its analogs have been shown to have major drawbacks (i.e., intrinsic and acquired chemoresistance, high general toxicity and limited spectrum of activity) [26] which have motivated extensive investigations into alternative metal-based cancer therapies that effectively target both cancer cell proliferation and metastasis. In this sense, we can mention chemotherapy with gold compounds [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]-because they are nontoxic, nonimmunogenic and have good photothermal and optical properties, biocompatibility and stability [40,47,48]-and also with copper [49][50][51], ruthenium [16,[52][53][54][55][56][57][58][59], iron [56,[60][61][62][63][64][65], palladium [50], silver [66,…”