Hypoxia-activated ROS burst liposomes boosted by local mild hyperthermia for photo/chemodynamic therapy.

Single reactive oxygen species (ROS)-mediated therapy, photodynamic therapy (PDT) or chemodynamic therapy (CDT) is severely hindered in hypoxic solid tumor. Herein, to address the urgent challenge, a hypoxia-activated ROS burst liposome has been fabricated to achieve synergistic PDT/CDT that is initiated by the structural dissociation of poly(metronidazole) liposome in hypoxic tumor microenvironment (TME). The therapeutic enhancement of our ROS-blasting treatment is simultaneously regulated by external light-initiated PDT and endogenous iron oxide nanoclusters-triggered CDT, which is synergistically boosted and amplified by localized mild hyperthermia under 808/660 nm coirradiation. More importantly, in vitro and in vivo experiments demonstrate that electron-affinic poly(aminoimidazole) product from hypoxia-responsive transition of poly(metronidazole) polymers could efficiently enhance hypoxic cell apoptosis and induce solid tumor ablation. Thus, this work offers a potential hypoxia-activated ROS burst-PDT/CDT strategy with a superior antitumor efficacy, highlighting a promising clinical application.

Near-infrared light-activated red-emitting upconverting nanoplatform for T1-weighted magnetic resonance imaging and photodynamic therapy.

Photodynamic therapy (PDT) has increasingly become an efficient and attractive cancer treatment modality based on reactive oxygen species (ROS) that can induce tumor death after irradiation with ultraviolet or visible light. Herein, to overcome the limited tissue penetration in traditional PDT, a novel near-infrared (NIR) light-activated NaScF4: 40% Yb, 2% Er@CaF2 upconversion nanoparticle (rUCNP) is successfully designed and synthesized. Chlorin e6, a photosensitizer and a chelating agent for Mn2+, is loaded into human serum albumin (HSA) that further conjugates onto rUCNPs. To increase the ability to target glioma tumor, an acyclic Arg-Gly-Asp peptide (cRGDyK) is linked to rUCNPs@HSA(Ce6-Mn). This nanoplatform enables efficient adsorption and conversion of NIR light (980 nm) into bright red emission (660 nm), which can trigger the photosensitizer Ce6-Mn complex for PDT and T1-weighted magnetic resonance imaging (T1-weighted MRI) for glioma diagnosis. Our in vitro and in vivo experiments demonstrate that NIR light-activated and glioma tumor-targeted PDT can generate large amounts of intracellular ROS that induce U87 cell apoptosis and suppress glioma tumor growth owing to the deep tissue penetration of irradiated light and excellent tumor-targeting ability. Thus, this nanoplatform holds potential for applications in T1-weighted MRI diagnosis and PDT of glioma for antitumor therapy. STATEMENT OF SIGNIFICANCE: A near-infrared (NIR) light-activated nanoplatform for photodynamic therapy (PDT) was designed and synthesized. The Red-to-Green (R/G) ratio of NaScF4: 40% Yb, 2% Er almost reached 9, a value that was much higher than that of a traditional Yb/Er-codoped upconversion nanoparticle (rUCNP). By depositing a CaF2 shell, the red-emission intensities of the rUCNPs were seven times strong as that of NaScF4: 40% Yb, 2% Er. The enhanced red-emitting rUCNPs could be applied in many fields such as bioimaging, controlled release, and real-time diagnosis. The nanoplatform had a strong active glioma-targeting ability, and all results achieved on subcutaneous glioma demonstrated that our NIR light-activated red-emitting upconverting nanoplatform was efficient for PDT. By loading Ce6-Mn complex into rUCNPs@HSA-RGD, the nanoplatform could be used as a T1-weighted magnetic resonance imaging agent for tumor diagnosis.

pH-Responsive Magnetic Mesoporous Silica-Based Nanoplatform for Synergistic Photodynamic Therapy/Chemotherapy.

By overcoming drug resistance and subsequently enhancing the treatment, the combination therapy of photodynamic therapy (PDT) and chemotherapy has promising potential for cancer treatment. However, the major challenge is how to establish an advanced nanoplatform that can be efficiently guided to tumor sites and can then stably release both chemotherapy drugs and a photosensitizer simultaneously and precisely. In this study, which considered the possibility and targeting efficiency of a magnetic targeting strategy, a novel Fe3O4@mSiO2(DOX)@HSA(Ce6) nanoplatform was successfully built; this platform could be employed as an efficient synergistic antitumor nanoplatform with magnetic guidance for highly specific targeting and retention. Doxorubicin (DOX) molecules were loaded into mesoporous silica with high loading capability, and the mesoporous channels were blocked by a polydopamine coating. Human serum albumin (HSA) was conjugated to the outer surface to increase the biocompatibility and blood circulation time, as well as to provide a vehicle for loading photosensitizer chlorin e6 (Ce6). The sustained release of DOX under acidic conditions and the PDT induced by red light exerted a synergistic inhibitory effect on glioma cells. Our experiments demonstrated that the pH-responsive Fe3O4@mSiO2(DOX)@HSA(Ce6) nanoplatform was guided to the tumor region by magnetic targeting and that the nanoplatform suppressed glioma tumor growth efficiently, implying that the system is a highly promising photodynamic therapy/chemotherapy combination nanoplatform with synergistic effects for cancer treatment.

Application of nanosized Fe3O4 in anticancer drug carriers with target-orientation and sustained-release properties.

The purpose of this study was to prepare human serum albumin (HSA) microspheres with Fe(3)O(4) magnetic nanoparticles for tumor target therapy. Fe(3)O(4) was obtained by liquid-phase coprecipitation; HSA-coated magnetic particles were attained by solidification at high temperature. The result was that nanosized Fe(3)O(4) is a cubic crystal by XRD and the average size is 18.7 nm; the average size of HSA-coated magnetic particles is 341 nm. Fe(3)O(4) magnetic nanoparticles coated with HSA can be used for targeted-drug carriers with target-orientation and sustained-release properties.