A Dual Functional Nanoreactor for Synergistic Starvation and Photodynamic Therapy

Abstract

The combination of photodynamic therapy (PDT) and enzyme therapy is a highly desirable approach in malignant tumor therapies as it takes advantage of the spatial-controlled PDT and the effective enzyme-catalyzed bioreactions. However, it is a challenge to co-encapsulate hydrophilic enzymes and hydrophobic photosensitizers, and these two agents often interfere with each other. In this work, a protocell-like nanoreactor (GOx-MSN@MnPc-LP) has been designed for synergistic starvation therapy and PDT. In this nanoreactor, the hydrophilic glucose oxidase (GOx) is loaded in the pore of mesoporous silica nanoparticles (MSNs), while the hydrophobic manganese phthaleincyanide (MnPc) is loaded in the membrane layer of liposome. This spatial separation of two payloads protects GOx and MnPc from the cellular environment and avoids interference with each other. GOx catalyzes the oxidation of glucose, which generates hydrogen peroxide and gluconic acid, leading to the starvation therapy via glucose consumption in cancer cells, as well as the disruption of cellular redox balance. MnPc produces cytotoxic singlet oxygen under 730 nm laser irradiation, achieving PDT. The antitumor effects of the nanoreactor have been verified on tumor cells and tumor-bearing mice models. GOx-MSN@MnPc-LP efficiently inhibits tumor growth in vivo with a single treatment, indicating the robust synergy of starvation therapy and PDT treatment. This work also offers a versatile strategy for delivering hydrophilic enzymes and hydrophobic photosensitizers using a protocell-like nanoreactor for effective cancer treatment.

Tumor Microenvironment‐“AND” Near‐Infrared Light‐Activated Coordination Polymer Nanoprodrug for On‐Demand CO‐Sensitized Synergistic Cancer Therapy

“…[ 14 ] The highly treatment efficient of CDT drug is due to the generation of the large amounts of highly toxic hydroxyl radicals (•OH) producted by Fenton‐like reaction between hydrogen peroxide (H 2 O 2 ) and catalysts. [ 10e,15 ] In addition, the latest research shows that the photodynamic therapy could promote the cellular uptake of nanoreagents because such procedure is constantly accompanied by the production of H 2 O 2 in the cell. [ 2 ] Moreover, CDT should do that because itself is also a reactive oxygen species (ROS) therapy strategy.…”

An Update on Mesoporous Silica Nanoparticle Applications in Nanomedicine

“…Furthermore, MSNs have also been used to co-encapsulate agents that might interfere with each other. For example, the GOx-MSN@MnPc-LP nanoparticles have been designed to co-deliver hydrophilic enzymes and hydrophobic photosensitizers [ 356 ]. These MSNs are simultaneously loaded with the hydrophilic glucose oxidase (GOx) and the hydrophobic manganese phthaleincyanide (MnPc) in different compartments, demonstrating the combinatory effects of different agents in inhibiting tumor growth in spatially controlled PDT.…”

A Novel H2O2 Generator for Tumor Chemotherapy-Enhanced CO Gas Therapy

“…As a new metal-organic framework (MOF), ZIF-8 has good drug delivery properties and biocompatibility (17)(18)(19)(20)(21). Compared to other metal-organic framework (MOF) materials (22)(23)(24)(25)(26), ZIF-8 has several unique characteristics. ZIF-8 comprises 2-methylimidazole and Zn 2+ .…”