Elemental tellurium (Te) nanoparticles are increasingly important in a variety of applications such as thermoelectricity, photoconductivity, and piezoelectricity. However, they have been explored ...with limited success in their biomedical use, and thus a tremendous challenge still exists in the exploration of Te nanoparticles that can treat tumors as an effective anticancer agent. Here, we introduce bifunctional Te nanodots with well-defined nanostructure as an effective anticancer agent for photo-induced synergistic cancer therapy with tumor ablation, which is accomplished using hollow albumin nanocages as a nanoreactor. Under near-infrared light irradiation, Te nanodots can produce effective photothermal conversion, as well as highly reactive oxygen species such as •O2 – and dismutated •OH via a type-I mechanism through direct electron transfer, thereby triggering the potent in vivo hyperthermia and simultaneous intracellular reactive oxygen species at tumors. Moreover, Te nanodots possess perfect resistance to photobleaching, effective cytoplasmic translocation, preferable tumor accumulation, as well as in vivo renal elimination, promoting severe photo-induced cell damage and subsequent synergy between photothermal and photodynamic treatments for tumor ablation. These findings provide the insight of elemental Te nanodots for biomedical research.
Photodynamic therapy (PDT), as an emerging clinically approved modality, has been used for treatment of various cancer diseases. Conventional PDT strategies are mainly focused on superficial lesions ...because the wavelength of illumination light of most clinically approved photosensitizers (PSs) is located in the UV/VIS range that possesses limited tissue penetration ability, leading to ineffective therapeutic response for deep‐seated tumors. The combination of PDT and nanotechnology is becoming a promising approach to fight against deep tumors. Here, the rapid development of new PDT modalities based on various smartly designed nanocomposites integrating with conventionally used PSs for deep tumor treatments is introduced. Until now many types of multifunctional nanoparticles have been studied, and according to the source of excitation energy they can be classified into three major groups: near infrared (NIR) light excited nanomaterials, X‐ray excited scintillating/afterglow nanoparticles, and internal light emission excited nanocarriers. The in vitro and in vivo applications of these newly developed PDT modalities are further summarized here, which highlights their potential use as promising nano‐agents for deep tumor therapy.
Photodynamic therapy (PDT) for deep tumor treatment is largely limited by light penetration depth in tissue. To address this issue, various strategies based on nanomaterials including near infrared excited PDT, X‐ray excited PDT and internal light emission excited PDT have been proposed. This article provides a comprehensive review of the rapid development of these new PDT modalities.
Transition metal sulfide nanocrystals are developed as a theranostic platform through the protein‐nanoreactor approach with facile functionalization for multimodal NIRF/PA/SPECT/CT imaging and ...photothermal tumor ablation.
Photodynamic therapy (PDT) for deep-seated tumor is largely impeded by the limited penetration depth of excitation light in tissue. X-ray is considered as an ideal energy source to activate ...photosensitizers (PSs) located deep within the body with the assistance of scintillating nanoparticles (ScNPs). However, the efficacy under this concept is not satisfying due to the low scintillating luminescence and weak energy transfer from ScNPs to PSs. Here, mesoporous LaF3:Tb ScNPs were successfully synthesized by a facile hydrothermal process to act as PS carriers and X-ray energy transducers, owing to their good ionizing radiation stopping power and high luminescence efficiency. The formation mechanism of porous structure was elucidated in detail with classical crystallization theory. After a systematic investigation, LaF3:Tb ScNPs with optimized scintillating luminescence were obtained for loading Rose Bengal (RB) to establish an efficient FRET system, owing to their excellent spectral match. The FRET efficiency between ScNPs and RB was calculated to be as high as 85%. Under irradiation, enhanced 1O2 generation induced by LaF3:Tb-RB nanocomposites via FRET process was detected. This LaF3:Tb-RB FRET system shows great potential to be applied in X-ray stimulated PDT for deep-seated tumors in the future.
Titanium dioxide nanoparticles (TiO
2
-NPs) are commonly used as food additives, including some high-fat foods that are risk factors for obesity. However, little is known about the effects of chronic ...TiO
2
-NPs digestion in the population on high fat diet (HFD). Herein, we reported that TiO
2
-NPs exacerbated HFD-induced obesity by disruption of mucus layer and alterations of gut microbiota. Oral intake of TiO
2
-NPs significantly increased body weight, liver weight, and amount of adipose tissues, especially in HFD-fed mice. Mechanistic studies revealed TiO
2
-NPs induced colonic mucus layer disruption and obesity-related microbiota dysbiosis. The damage on mucus was demonstrated through down-regulation of
Muc2
gene and the absorption of mucin protein by TiO
2
-NPs. Consequently, mucus layer damage combined microbiota dysbiosis escalated the low-grade systemic inflammation, which exacerbated HFD-induced obesity. In contrast, gut microbiota depletion eliminated these effects, indicating gut microbiota were necessary for TiO
2
-NPs-induced inflammation and obesity. All the results stated the alarming role of TiO
2
-NPs in the HFD-driven obesity and emphasized the reevaluating the health impacts of nanoparticles commonly used in daily life, particularly, in susceptible population.
Glioblastoma multiforme (GBM) is one of the most fatal malignancies due to the existence of blood-brain barrier (BBB) and the difficulty to maintain an effective drug accumulation in deep GBM ...lesions. Here we present a biomimetic nanogel system that can be precisely activated by near infrared (NIR) irradiation to achieve BBB crossing and deep tumor penetration of drugs. Synthesized by crosslinking pullulan and poly(deca-4,6-diynedioic acid) (PDDA) and loaded with temozolomide and indocyanine green (ICG), the nanogels are inert to endogenous oxidative conditions but can be selectively disintegrated by ICG-generated reactive oxygen species upon NIR irradiation. Camouflaging the nanogels with apolipoprotein E peptide-decorated erythrocyte membrane further allows prolonged blood circulation and active tumor targeting. The precisely controlled NIR irradiation on tumor lesions excites ICG and deforms the cumulated nanogels to trigger burst drug release for facilitated BBB permeation and infiltration into distal tumor cells. These NIR-activatable biomimetic nanogels suppress the tumor growth in orthotopic GBM and GBM stem cells-bearing mouse models with significantly extended survival.
Abstract
Combining immune checkpoint blockade (ICB) therapy with photodynamic therapy (PDT) holds great potential in treating immunologically “cold” tumors, but photo-generated reactive oxygen ...species (ROS) can inevitably damage co-administered ICB antibodies, hence hampering the therapeutic outcome. Here we create a ROS-responsive hydrogel to realize the sustained co-delivery of photosensitizers and ICB antibodies. During PDT, the hydrogel skeleton poly(deca-4,6-diynedioic acid) (PDDA) protects ICB antibodies by scavenging the harmful ROS, and at the same time, triggers the gradual degradation of the hydrogel to release the drugs in a controlled manner. More interestingly, we can visualize the ROS-responsive hydrogel degradation by Raman imaging, given the ultrastrong and degradation-correlative Raman signal of PDDA in the cellular silent window. A single administration of the hydrogel not only completely inhibits the long-term postoperative recurrence and metastasis of 4T1-tumor-bearing mice, but also effectively restrains the growth of re-challenged tumors. The PDDA-based ROS-responsive hydrogel herein paves a promising way for the durable synergy of PDT and ICB therapy.
Live-cell Raman imaging based on bioorthogonal Raman probes with distinct signals in the cellular Raman-silent region (1800-2800 cm
) has attracted great interest in recent years. We report here a ...class of water-soluble and biocompatible polydiacetylenes with intrinsic ultrastrong alkyne Raman signals that locate in this region for organelle-targeting live-cell Raman imaging. Using a host-guest topochemical polymerization strategy, we have synthesized a water-soluble and functionalizable master polydiacetylene, namely poly(deca-4,6-diynedioic acid) (PDDA), which possesses significantly enhanced (up to ~10
fold) alkyne vibration compared to conventional alkyne Raman probes. In addition, PDDA can be used as a general platform for multi-functional ultrastrong Raman probes. We achieve high quality live-cell stimulated Raman scattering imaging on the basis of modified PDDA. The polydiacetylene-based Raman probes represent ultrastrong intrinsic Raman imaging agents in the Raman-silent region (without any Raman enhancer), and the flexible functionalization of this material holds great promise for its potential diverse applications.
Smart nanocarriers are of particular interest as nanoscale vehicles of imaging and therapeutic agents in the field of theranostics. Herein, we report dually pH/reduction-responsive terpolymeric ...vesicles with monodispersive size distribution, which are constructed by assembling acetal- and disulfide-functionalized star terpolymer with near-infrared cyanine dye and anticancer drug. The vesicular nanostructure exhibits multiple theranostic features including on-demand drug releases responding to pH/reduction stimuli, enhanced photothermal conversion efficiency of cyanine dye, and efficient drug translocation from lysosomes to cytoplasma, as well as preferable cellular uptakes and biodistribution. These multiple theranostic features result in ultrahigh-contrast fluorescence imaging and thermo-chemotherapy-synergized tumor ablation. The dually stimuli-responsive vesicles represent a versatile theranostic approach for enhanced cancer imaging and therapy.
Display omitted
•Tri-chamber nanofibers in the form of core–shell microstructure embedded on one side of the Janus main structure were designed.•Hydrophilic and pH sensitive polymers were combined ...skillfully in complicated structure nanocomposites.•The tri-chamber nanofibers facilitated the rapid release of quercetin and the delayed and sustained release of tamoxifen citrate.•The tri-chamber nanofibers could result in a synergistic anticancer action of quercetin and tamoxifen citrate.
A tri-fluid electrospinning process was successfully developed to prepare tri-chamber complex nanofibers. The core–shell and Janus structure were combined to form a delicate and complicated architecture for solving the problem of co-administration of quercetin and tamoxifen citrate, improving the oral bioavailability, and enhancing their synergistic anti-breast cancer actions. Scanning electron microscope, transmission electron microscope and confocal fluorescent microscopy images showed the complex structure of the designed nanofibers. Fourier transform infrared and X-ray diffraction analyses verified that the model drugs and the polymeric excipients had good compatibility and were presented in an amorphous state. The in vitro release study certified that the tri-chamber nanofibers facilitated the rapid release of quercetin compared with that of the crude drug (90% versus 38%) and the delayed and sustained release of tamoxifen citrate at the same time interval (decreased by 1.88 times). The in vivo pharmacokinetic and pharmacodynamic analysis verified that the tri-chamber nanofibers could result in increased oral bioavailability and enhanced synergistic anticancer action of quercetin and tamoxifen citrate. The findings proved that a new medicated drug delivery system with advanced dual-, time-, and target-specific drug release profiles was developed using the electrospun complex nanostructure.
PDF
