Significant progress is achieved for the utilization of graphene quantum dots as enzyme mimics in various biomedical fields recently. Although promising, the biocatalytic performance is far from satisfactory. Here, the rational design and synthesis of specific oxygenated groups enriched graphene quantum dots (o-GQDs) via a facile oxidation reflux route is reported. These well-prepared o-GQDs with uniform size exhibit an ultrahigh peroxidase-like activity in a wide range of pH values, and their superior performance is verified by using glucose detection as a typical model. Compared with classical nanozymes, these o-GQDs show multiple times higher enzymatic activity. It is believed that the super facile synthesis strategy can greatly facilitate the practical use of o-GQDs as enzyme mimics in the future.
Nanoscale porphyrinic metal–organic
frameworks (NMOFs) have emerged as promising therapeutic platforms
for the photodynamic therapy (PDT) of cancer in recent years. However,
the relatively large sizes of current NMOFs ranging from tens to hundreds
of nanometers usually lead to inefficient body clearance and unsatisfactory
PDT effect, thus amplifying their long-term toxicity and restricting
their further usage. To overcome these shortcomings, herein, ultrasmall
porphyrinic metal–organic framework nanodots (MOF QDs) prepared
from NMOFs are rationally synthesized via a facile
method and used as renal-clearable nanoagents for the enhanced PDT
of cancer. Compared with the precursor NMOFs, our well-prepared MOF
QDs can generate 2-fold effective toxic reactive oxygen species (ROS)
upon the same light irradiation and greatly decrease the inefficacy
of PDT caused by the inefficient use of ROS generated from the interior
of NMOFs. Meanwhile, the IC50 value of ultrasmall MOF QDs
is nearly one-third that of NMOFs, and in vivo results
demonstrate that our MOF QDs exhibit better PDT efficacy than NMOFs
under the same treatment owing to their overcoming the limited ROS
diffusion distance. Significantly, these ultrasmall MOF QDs show efficient
tumor accumulation and rapid renal clearance in vivo, indicating their potential in biomedical utility. Last but not
least, comprehensive investigations of long-term toxicity of these
MOF QDs well demonstrate their overall safety. Therefore, this study
will offer valuable insight into the development of safe and high-performance
PDT nanoplatforms for further clinical translation.
Acute kidney injury (AKI) is a syndrome characterized by rapid loss of renal excretory function with high in-hospital mortality. The excess generation of reactive oxygen species (ROS) in kidneys during...
Ultrasound (US)-mediated sonodynamic therapy (SDT) has been emerged as a spatiotemporally controllable therapeutic modality in combating cancer because of its high tissue-penetration depth and minimal invasiveness. However, the elevated nuclear...
Physiological
microenvironment engineering has shown great promise
in combating a variety of diseases. Herein, we present the rational
design of reinforced and injectable blood-derived protein hydrogels
(PDA@SiO2-PRF) composed of platelet-rich fibrin (PRF),
polydopamine (PDA), and SiO2 nanofibers that can act as
dual-level regulators to engineer the microenvironment for personalized
bone regeneration with high efficacy. From the biophysical level,
PDA@SiO2-PRF with high stiffness can withstand the external
loading and maintaining the space for bone regeneration in bone defects.
Particularly, the reinforced structure of PDA@SiO2-PRF
provides bone extracellular matrix (ECM)-like functions to stimulate
osteoblast differentiation via Yes-associated protein (YAP) signaling
pathway. From the biochemical level, the PDA component in PDA@SiO2-PRF hinders the fast degradation of PRF to release autologous
growth factors in a sustained manner, providing sustained osteogenesis
capacity. Overall, the present study offers a dual-level strategy
for personalized bone regeneration by engineering the biophysiochemical
microenvironment to realize enhanced osteogenesis efficacy.
Autologous blood-derived protein hydrogels have shown great promise in the field of personalized regenerative medicine. However, the inhospitable regenerative microenvironments, especially the unfavorable immune microenvironment, are closely associated with their limited tissue-healing outcomes. Herein, novel immunomodulatory blood-derived hybrid hydrogels (PnP-iPRF) are rationally designed and constructed for enhanced bone regeneration via multichannel regulation of the osteogenic microenvironment. Such double-network hybrid hydrogels are composed of clinically approved injectable platelet-rich fibrin (i-PRF) and polycaprolactone/hydroxyapatite composite nanofibers by using enriched polydopamine (PDA) as the anchor. The polycaprolactone component in PnP-iPRF provides a reinforced structure to stimulate osteoblast differentiation in a proper biomechanical microenvironment. Most importantly, the versatile PDA component in PnP-iPRF can not only offer high adhesion capacity to the growth factors of i-PRF and create a suitable biochemical microenvironment for sustained osteogenesis but also reprogram the osteoimmune microenvironment via the induction of M2 macrophage polarization to promote bone healing. The present study will provide a new paradigm to realize enhanced osteogenic efficacy by multichannel microenvironment regulations and give new insights into engineering high-efficacy i-PRF hydrogels for regenerative medicine.
Chemotherapeutic drug-induced acute kidney injury (AKI) involves pathologically increased labile iron species in the kidneys that mediate the excessive generation of reactive oxygen species (ROS) to induce ferroptosis and apoptosis, subsequently driving renal dysfunction. Herein, we report renal clearable quantum dot−drug conjugates (QDCs) composed of carbon quantum dot (CDs), deferoxamine (DFO), and poly(ethylene glycol) (PEG) for attenuating chemotherapeutic drug-induced AKI. The CDs component in QDCs can not only provide DFO with high renal specificity to effectively remove the pathological labile iron species in the kidneys to block the source of ROS generation but also exert high antioxidative effects to avoid renal oxidative damage caused by the ROS that have been overproduced. In cisplatin-induced AKI mice, QDCs can inhibit ferroptosis and apoptosis with high efficacy for AKI treatment. This study will provide a new paradigm to realize enhanced therapeutic efficacy for AKI by simultaneously removing the pathological labile iron species and eliminating overproduced ROS in the kidneys to achieve the goal of addressing both symptoms and root causes.
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