Hypoxia-active nanoparticles used in tumor theranostic

Abstract

Hypoxia is a hallmark of malignant tumors and often correlates with increasing tumor aggressiveness and poor treatment outcomes. Therefore, early diagnosis and effective killing of hypoxic tumor cells are crucial for successful tumor control. There has been a surge of interdisciplinary research aimed at developing functional molecules and nanomaterials that can be used to noninvasively image and efficiently treat hypoxic tumors. These mainly include hypoxia-active nanoparticles, anti-hypoxia agents, and agents that target biomarkers of tumor hypoxia. Hypoxia-active nanoparticles have been intensively investigated and have demonstrated advanced effects on targeting tumor hypoxia. In this review, we present an overview of the reports published to date on hypoxia-activated prodrugs and their nanoparticle forms used in tumor-targeted therapy. Hypoxia-responsive nanoparticles are inactive during blood circulation and normal physiological conditions but are activated by hypoxia once they extravasate into the hypoxic tumor microenvironment. Their use can enhance the efficiency of tumor chemotherapy, radiotherapy, fluorescence and photoacoustic intensity, and other imaging and therapeutic strategies. By targeting the broad habitats of tumors, rather than tumor-specific receptors, this strategy has the potential to overcome the problem of tumor heterogeneity and could be used to design diagnostic and therapeutic nanoparticles for a broad range of solid tumors.

Keywords: bioreductive; metal complex; prodrug; tumor microenvironment.

Figure 1

Structure and activation of metal complex. (A) complex Ir, (B) [Ru(dpp)₃]²⁺ (C) Pt(II) porphyrins (D) Oxygen sensing mechanism of conjugated polyelectrolyte and schematic illumination of energy level of the moieties in phosphorescent transition-metal S₀, ground state, S₁- excited singlet states by fluorescence light, T₁- triplet state form by S₁ intersystem crossing, 1Δ_g-1Σg+.

Figure 2

Activation mechanical of HAP. (A) 5-Nitroimidazole reduced through one electron pathway. (B) AQ4N reduced through two electron pathway (C) Tirapazamine reduced through one electron pathway to form DNA toxic.

Figure 3

The hypoxia-activated phototrigger specifically releases drug to tumor cells.

Figure 4

(A) Schematic of how the light-activated Dox@NP nanoparticles worked in combined combining hypoxia-triggered and PDT treatment strategy. (B) Generation of the ROS and hypoxia-induced disassembly upon laser irradiation. The mechanism of (C) photosensitized reaction induced by Ce6 and (D) stepwise reduction of azobenzene in hypoxia environment9. (E) light-driven synergistic therapy of ROS and Dox-based chemotherapy.