Engineered gold/black phosphorus nanoplatforms with remodeling tumor microenvironment for sonoactivated catalytic tumor theranostics

Abstract

The imbalance between oxidants and antioxidants in cancer cells would evoke oxidative stress-induced cell death, which has been demonstrated to be highly effective in treating malignant tumors. Sonodynamic therapy (SDT) adopts ultrasound (US) as the excitation source to induce the production of reactive oxygen species (ROS), which emerges as a noninvasive therapeutic strategy with deep tissue penetration depth and high clinical safety. Herein, we construct novel sonoactivated oxidative stress amplification nanoplatforms by coating MnO 2 on Au nanoparticle-anchored black phosphorus nanosheets and decorating soybean phospholipid subsequently (Au/BP@MS). The Au/BP@MS exhibit increased ROS generation efficiency under US irradiation in tumor tissues due to Au/BP nanosensitizer-induced improvement of electron-hole separation as well as MnO 2 -mediated O 2 generation and GSH depletion, thus leading to notable inhibition effect on tumor growth. Moreover, tumor microenvironment-responsive biodegradability of Au/BP@MS endows them with enhanced magnetic resonance imaging guidance and clinical potential for cancer theranostics.

Nanomaterials-Based Tumor Microenvironment Modulation for Magnifying Sonodynamic Therapy

“…Very recently, research on developing novel manganese/iron oxide based nanocomposites as SDT regimens to deplete overexpressed H 2 O 2 , release O 2 , and decrease GSH is receiving more attention to break redox homeostasis and increase ROS levels for suppressing tumors. 4,9,29,30,32 In some typical cases, Fu et al used hollow mesoporous organosilica nanoparticles (HMON) as vehicles to immobilize protoporphyrin IX (PpIX) sonosensitizers and simultaneously load peroxynitrite (VI), highly reactive water, hydrogen peroxide, and phase-changeable medium (lauric acid, LA), obtained an ultrasound-activation multifunctional nanosystem (FHPLP) for highly efficient SDT against hypoxic osteosarcoma. 4 The thermal effect of ultrasonic irradiation can trigger the phase transition of LA, which ensures the controllable release of O 2 and ROS after the occurrence of PpIX-unlocked SDT and intracellular Fenton reaction between peroxynitrite (VI) and H 2 O 2 .…”

“…In addition, Mn-based nanosystems also share the identical actions after rational engineering, such as hollow manganese dioxide (HMnO 2 ) nanostructures. 9,29,30,40 Our group also did an innovative job where combining HMnO 2 with tyrosinasetriggered oxidative stress amplifier (APAP) was implemented. 29 HMnO 2 could react with intratumoral H 2 O 2 to release O 2 to reverse tumor hypoxia and enhance ROS production (Figure 3h) and also boost GSH consumption to attain redox homeostasis disruption and amplify oxidative stress for resisting tumor growth (Figure 3i).…”

“…Different TMEs decide different tumor fates; e.g. , hypoxia and an immunosuppressive microenvironment manipulate cancer development and progression. , More significantly, these different TMEs may activate multiple pathways to compromise or even impair SDT via enhancing tumor resistance, consuming ROS, inactivating immune responses, etc. − In recent years, great breakthroughs have been made in developing TEM-engineered nanomaterials or nanobiotechnologies to provide targeted modulation of various TMEs, which furnished adequate tools or ammunition to arm sonosensitizers to SDT and to magnify SDT efficacy.…”

Potential of Black Phosphorus in Immune-Based Therapeutic Strategies

“…Liu et al discovered that covalent modification, especially benzoic-acid-functionalized BP, can promote the formation of OH − as one of the components of ROS [ 82 ]. On the side, Chen's team employed Au-anchored BP to enhance sensitivity of sound sonosensitizers and employed MnO 2 shell encapsulated BP to enhance antioxidant depletion, both of which amplified the generation efficiency of ROS [ 83 ]. Therefore, SDT is another major innovation followed phototherapy and gives new opportunities for clinical antitumor therapy.…”

A Two‐In‐One Nanoprodrug for Photoacoustic Imaging‐Guided Enhanced Sonodynamic Therapy

“…[11][12][13][14][15] However, SDT relies on ultrasound (US) that has greater penetrative power and can therefore reach deep-seated tumors. [16][17][18][19][20][21] Despite its clinical potential, the efficacy of SDT is also limited due to the lack of safe sonosensitizers and the highly reductive environment of tumor cells that neutralize the ROS produced during SDT. [22,23] Therefore, it is crucial to design sonosensitizers that can change the reductive intracellular environment while satisfying biological safety for the clinical application of SDT.…”