A Simple and Efficient Embolization-Combined Therapy for Solid Tumors by Smart Poly(amino acid)s Nanocomposites

Abstract

Interventional embolization and minimally invasive thermal ablation are common clinical methods for treatment of unresectable solid tumors, but they both have many insurmountable disadvantages. Inspired by pH-responsive drug delivery systems, we report the tumor microenvironment-gelled nanocomposites with poly­[(l-glutamic acid-ran-l-tyrosine)-b-l-threonine-b-l-cysteine]­s (PGTTCs) coating nanoparticles (NPs, Au or Fe3O4) for noninterventional targeted embolization combined with noninvasive thermal ablation therapy of solid tumors by intravenous injection without catheter use. The results of the animal trial in vivo with tumor-bearing mice and rabbits showed superior targeted embolization and therapy and fluorescence/single-photon emission computed tomography/magnetic resonance multimodal imaging effects. Tumors treated with NPs@PGTTCs were shrunken and necrotized within 30 days, the long-term survival rate was more than 80%, and the same effects can be achieved within 15 days when combined with thermal ablation. The method is so simple and efficient for many hard-to-treat tumors within an acidic microenvironment, which is not only a great improvement and innovation in tumor theranostics but also an important development in nanomedicine.

Recent Progress in Advanced Hydrogel‐Based Embolic Agents: From Rational Design Strategies to Improved Endovascular Embolization

“…A variety of embolic materials have been developed gradually, and more research interests have been focused on the development of smart and/or multifunctional embolic materials. The hydrogel-based embolic agents possess appropriate gelation triggers to avoid the blockage of the catheter and proper viscosities to occlude the target vasculature with various geometries [46] Copyright 2022, American Chemical Society. and sizes.…”

“…In vivo study on tumor-bearing mice demonstrated the synergistic therapeutic effect of embolization and magnetic hyperthermia therapy (Figure 17E,F). [46] In addition, to break through the limited penetration depth of photothermal therapy in treating some tumors, Qian et al prepared a magnetic field-responsive hydrogel composed of silk fibroin (SF) and iron oxide nanotubes (IONCs). The incorporation of IONCs in SF hydrogel (FSH) rarely affected the shear-thinning behavior of SF hydrogel, which facilitated the injection of the composite hydrogel into the deep tumor region.…”

“…Besides these mentioned properties, the hydrogel-based embolic agents can be designed to load therapeutic drugs, [34,[42][43][44] bioactive molecules, [45] and functional nanomaterials. [37,46,47] The developed hybrid hydrogel platforms provide controlled drug delivery in the site of action, local procoagulant activity, realtime imaging visibility, and thermal ablation, which make them more effective for various disease treatments. As for hydrogel coils, recent studies indicated that the introduction of different physical interactions such as hydrophobic interactions, [48] hydrogen bonds, [49] dipole-dipole interactions, [28] and crystalline domains [50] into the hydrophilic hydrogel networks can obtain the stimuli-responsive shape memory hydrogels (SMHs).…”

Recent advances in smart nanoplatforms for tumor non-interventional embolization therapy

“…In addition to the abovementioned materials, pH-responsive polymers can also be used as embolic materials [ 80 , 81 ]. When an aqueous solution of a polymer embolic agent whose responsive pH value is similar to or the same as the pH of the acidic TME is injected into the tumor site, the polymer solution will change from sol to gel as the pH of the tumor tissue decreases, thereby blocking the tumor blood vessels and achieving the purpose of tumor growth inhibition.…”

“…When an aqueous solution of a polymer embolic agent whose responsive pH value is similar to or the same as the pH of the acidic TME is injected into the tumor site, the polymer solution will change from sol to gel as the pH of the tumor tissue decreases, thereby blocking the tumor blood vessels and achieving the purpose of tumor growth inhibition. Based on that, Lu et al developed PGTTCs-coated Au or Fe 3 O 4 NPs for tumor noninterventional targeted embolization and thermal therapy [ 81 ]. The smart composites could change from sol to gel in an acidic microenvironment, thus occluding the blood vessels of tumors after intravenous injection to inhibit tumor growth to some extent.…”