Metalloporphyrin-Encapsulated Biodegradable Nanosystems for Highly Efficient Magnetic Resonance Imaging-Guided Sonodynamic Cancer Therapy

Abstract

Traditional photodynamic therapy (PDT) suffers from the critical issues of low tissue-penetrating depth of light and potential phototoxicity, which are expected to be solved by developing new dynamic therapy-based therapeutic modalities such as sonodynamic therapy (SDT). In this work, we report on the design/fabrication of a high-performance multifunctional nanoparticulate sonosensitizer for efficient in vivo magnetic resonance imaging (MRI)-guided SDT against cancer. The developed approach takes the structural and compositional features of mesoporous organosilica-based nanosystems for the fabrication of sonosensitizers with intriguing theranostic performance. The well-defined mesoporosity facilitates the high loading of organic sonosensitizers (protoporphyrin, PpIX) and further chelating of paramagnetic transitional metal Mn ions based on metalloporphyrin chemistry (MnPpIX). The mesoporous structure of large surface area also maximizes the accessibility of water molecules to the encapsulated paramagnetic Mn ions, endowing the composite sonosensitizers with markedly high MRI performance (r = 9.43 mM s) for SDT guidance and monitoring. Importantly, the developed multifunctional sonosensitizers (HMONs-MnPpIX-PEG) with controllable biodegradation behavior and high biocompatibility show distinctively high SDT efficiency for inducing the cancer-cell death in vitro and suppressing the tumor growth in vivo. This report provides a paradigm that nanotechnology-enhanced SDT based on elaborately designed high-performance multifunctional sonosensitizers will pave a new way for efficient cancer treatment by fully taking the advantages (noninvasiveness, convenience, cost-effectiveness, etc.) of ultrasound therapy and quickly developing nanomedicine.

A Multifunctional Biodegradable Nanocomposite for Cancer Theranostics

“…2019, 6, 1802001 and free ICG (Figure 6e). [14,45] Quantitative analysis of the ICG fluorescence intensity distribution in the organs and tumor is shown in Figure S15 of the Supporting Information, and is in agreement with the ex vivo fluorescence imaging. These results confirmed that ICG/PFP@ HMOP-PEG could effectively extend the blood circulation time of ICG due to the PTX prodrug capping and PEGylation.…”

“…These not only enhance the tumor cell uptake of the nanoparticles (Figure 4e-h), but also serve as an ultrasound imaging agent (Figure 4a). [14,15] HMONs and other mesoporous silica systems have been constructed for the delivery of PFP and perfluorohexane in several recent studies, [18,27] and found to act as potent bubble generators. [14,15] HMONs and other mesoporous silica systems have been constructed for the delivery of PFP and perfluorohexane in several recent studies, [18,27] and found to act as potent bubble generators.…”

“…[7][8][9] The latter are similar to mesoporous silicas, but rather than comprising pure SiO 2 contain organic functional groups within the silica framework. [14][15][16][17] For instance, Huang et al fabricated hollow MONs with a physiologically active disulfide bond (SS) incorporated into the silica framework. [10,11] Various organic moieties can be incorporated into MONs, and since these are intrinsic components of the framework they do not block the pore channels.…”

Engineering of inorganic nanoparticles as magnetic resonance imaging contrast agents

“…In addition, the well-defined mesoporosity of HMSNs can enable efficient encapsulation of photosensitizers ( i.e ., protoporphyrin) for therapeutic purposes, as well as further confinement of paramagnetic Mn ions based on metalloporphyrin chelating chemistry. 188 This mesoporous structure endowed these intriguing sensitizers with remarkably enhanced MRI performance ( r 1 = 9.43 mM −1 s −1 ).…”

Theranostic nanosensitizers for highly efficient MR/fluorescence imaging‐guided sonodynamic therapy of gliomas

“…The optical and T 1 relaxation properties of DVDMS‐Mn‐LPs hold promises for dual‐mode contrast agent for fluorescence and MR imaging of tumours (Figure ). In fact, abundant macromolecules and nanoparticles have been used as platforms for manganese loading, resulting in improved r 1 value of chelated Mn 2+ (generally between 5 and 30 per mmol/L per seconds) . In our study, the r 1 value for DVDMS‐Mn‐LPs was about 4‐fold higher than that of the clinical approved Magnevist due to increased local concentration of Mn 2+ and lowered molecular tumbling rate in those nanocarrier systems .…”