Multifunctional Tumor pH-Sensitive Self-Assembled Nanoparticles for Bimodal Imaging and Treatment of Resistant Heterogeneous Tumors

Abstract

Nanoparticle-based diagnosis-therapy integrative systems represent an emerging approach to cancer treatment. However, the diagnostic sensitivity, treatment efficacy, and bioavailability of nanoparticles as well as the heterogeneity and drug resistance of tumors pose tremendous challenges for clinical implementation. We herein report on the fabrication of tumor pH-sensitive magnetic nanogrenades (termed PMNs) composed of self-assembled iron oxide nanoparticles and pH-responsive ligands. These PMNs can readily target tumors via surface-charge switching triggered by the acidic tumor microenvironment, and are further disassembled into a highly active state in acidic subcellular compartments that "turns on" MR contrast, fluorescence and photodynamic therapeutic activity. We successfully visualized small tumors implanted in mice via unique pH-responsive T1MR contrast and fluorescence, demonstrating early stage diagnosis of tumors without using any targeting agents. Furthermore, pH-triggered generation of singlet oxygen enabled pH-dependent photodynamic therapy to selectively kill cancer cells. In particular, we demonstrated the superior therapeutic efficacy of PMNs in highly heterogeneous drug-resistant tumors, showing a great potential for clinical applications.

Magnetic Nanoparticles for Precision Oncology: Theranostic Magnetic Iron Oxide Nanoparticles for Image-Guided and Targeted Cancer Therapy

“…For example, Ling et al developed tumor pH-sensitive magnetic nanogrenades that were composed of self-assembled IONPs and pH-responsive ligands. These pH-sensitive magnetic nanogrenades could target to tumor cells and disassembled into active compartments under acid conditions to produce MRI and fluorescent signals, which led to the detection of small tumors with a diameter of 3 mm [96]. In addition, future science group Review Zhu, Zhou, Mao & Yang IONP-based hybrid nanoparticles coated with gold or quantum dots required surface plasmon resonance effect [97].…”

Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy

“…These obstacles existing in the body could considerably prevent nanomedicine from reaching its targets in a sufficient drug concentration (7,8). To overcome these barriers, a variety of strategies have been envisioned (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Despite great advances, these strategies have mainly focused on one or a few biological barriers and led to suboptimal therapeutic effect.…”

Inorganic Nanocarriers Overcoming Multidrug Resistance for Cancer Theranostics

“…By combination with anti‐ABCG2 monoclonal antibodies (mAbs), anticancer drugs‐loaded iron oxide nanoparticles can significantly inhibit the proliferation and migration of CSCs, and further lead to an obvious suppression of tumor growth in CSC‐transplanted mice 76. Recently, Ling et al developed pH‐sensitive magnetic nanoparticles (PMNs), which can disassemble in the acidic tumor microenvironment ( Figure 3 A,B) and switch the surface charge of nanoparticles; this resulted in an increase in cell adsorption and permeation 77. In addition, the disassembly would bring pH‐responsive T1 MR contrast and fluorescence, which enabled early stage diagnosis of tumors (Figure 3C,D).…”

“…E) H&E and TUNEL staining of tumor tissue sections to determine treatment effectiveness in terms of tumor cell death by apoptosis. Adapted with permission 77. Copyright 2016, American Chemical Society.…”