Cancer is a leading public health problem worldwide. Its treatment remains a daunting challenge, although significant progress has been made in existing treatments in recent years. A large concern is the poor therapeutic effect due to lack of specificity and low bioavailability. Gene therapy has recently emerged as a powerful tool for cancer therapy. However, delivery methods limit its therapeutic effects. Exosomes, a subset of extracellular vesicles secreted by most cells, have the characteristics of good biocompatibility, low toxicity and immunogenicity, and great designability. In the past decades, as therapeutic carriers and diagnostic markers, they have caught extensive attention. This review introduced the characteristics of exosomes, and focused on their applications as delivery carriers in DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering RNA (siRNA), circular RNA (circRNA) and other nucleic acids. Meanwhile, their application in cancer therapy and exosome-based clinical trials were presented and discussed. Through systematic summarization and analysis, the recent advances and current challenges of exosome-mediated nucleic acid delivery for cancer therapy are introduced, which will provide a theoretical basis for the development of nucleic acid drugs.
Graphical Abstract
Nowadays, energy and environment have become the critical issues to determine the sustainability of the Earth. Freshwater crises, as a increasingly serious global problem, poses a great threat to our...
Understanding
the morphology and hemodynamics of cerebral vasculature
at large penetration depths and microscale resolution is fundamentally
important to decipher brain diseases. Among the various imaging technologies,
three-photon (3P) microscopy is of significance by virtue of its deep-penetrating
capability and submicron resolution, which especially benefits in vivo vascular imaging. Aggregation-induced emission luminogens
(AIEgens) have been recognized to be extraordinarily powerful as 3P
probes. However, systematic studies on the structure–performance
relationship of 3P AIEgens have been seldom reported. Herein, a series
of AIEgens has been designed and synthesized. By intentionally introducing
benzene rings onto electron donors (D) and acceptors (A), the molecular
distortion, conjugation strength, and the D–A relationship
can be facilely manipulated. Upon encapsulation with DSPE-PEG2000, the optimized AIEgens are successfully applied for 3P
microscopy with emission in the far-red/near-infrared-I (NIR-I, 700–950
nm) region under the near-infrared-III (NIR-III, 1600–1870
nm) excitation. Impressively, using mice with an opened skull, vasculature
within 1700 μm and a microvessel with a diameter of 2.2 μm
in deep mouse brain were clearly visualized. In addition, the hemodynamics
of blood vessels were well-characterized. Thus, this work not only
proposes a molecular design strategy of 3P AIEgens but also promotes
the performance of 3P imaging in cerebral vasculature.
Chemo-photothermal therapy based on nanoparticles has emerged as a promising strategy for cancer treatment. However, its therapeutic efficacy and application potential are largely subjected to the uncontrollability and biotoxicity of functional nanoplatforms. Herein, a novel biocompatible and biodegradable metal organic framework (MOF), which was constructed by growing crystalline zeolitic imidazolate framework-8 on gold nanoroad (Au@ZIF-8), was designed and fabricated for efficient drug loading and controlled release. Owing to the large surface area and guest-matching pore size of ZIF-8, doxorubicin (DOX) was successfully loaded into the Au@ZIF-8 with a high drug loading efficiency of ~ 37%. Under NIR light or weakly acidic environment, the ZIF-8 layer was quickly degraded, which resulted in an on-demand drug release in tumour site. More importantly, under the irradiation of near infrared (NIR) laser, highly efficient cancer treatment was achieved in both in vitro cell experiment and in vivo tumour-bearing nude mice experiment due to the synergistic effect of photothermal (PTT) therapy and chemotherapy. In addition, the in vivo study revealed the good biocompatibility of Au@ZIF-8. This work robustly suggested that Au@ZIF-8 could be further explored as a drug delivery system for chemo-photothermal synergistic therapy.
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