Bacterial infection is one of the most serious physiological conditions threatening human health. There is an increasing demand for more effective bacterial diagnosis and treatment through ...noninvasive theranostic approaches. Herein, a new strategy is reported to achieve in vivo metabolic labeling of bacteria through the use of MIL‐100 (Fe) nanoparticles (NPs) as the nanocarrier for precise delivery of 3‐azido‐d‐alanine (d‐AzAla). After intravenous injection, MIL‐100 (Fe) NPs can accumulate preferentially and degrade rapidly within the high H2O2 inflammatory environment, releasing d‐AzAla in the process. d‐AzAla is selectively integrated into the cell walls of bacteria, which is confirmed by fluorescence signals from clickable DBCO‐Cy5. Ultrasmall photosensitizer NPs with aggregation‐induced emission characteristics are subsequently designed to react with the modified bacteria through in vivo click chemistry. Through photodynamic therapy, the amount of bacteria on the infected tissue can be significantly reduced. Overall, this study demonstrates the advantages of metal–organic‐framework‐assisted bacteria metabolic labeling strategy for precise bacterial detection and therapy guided by fluorescence imaging.
A novel strategy for in vivo bacterial metabolic labeling and precise antibacterial therapy is developed based on the combination of a metal–organic framework (MOF) as a carrier for amino acid delivery and photosensitizers with aggregation‐induced emission characteristics for imaging and therapy. The formulated MOF‐assisted strategy represents a promising alternative to antibiotics in image‐guided antibacterial therapy.
Fluorescence and photoacoustic imaging have different advantages in cancer diagnosis; however, combining effects in one agent normally requires a trade-off as the mechanisms interfere. Here, based on ...rational molecular design, we introduce a smart organic nanoparticle whose absorbed excitation energy can be photo-switched to the pathway of thermal deactivation for photoacoustic imaging, or to allow opposed routes for fluorescence imaging and photodynamic therapy. The molecule is made of a dithienylethene (DTE) core with two surrounding 2-(1-(4-(1,2,2-triphenylvinyl)phenyl)ethylidene)malononitrile (TPECM) units (DTE-TPECM). The photosensitive molecule changes from a ring-closed, for photoacoustic imaging, to a ring-opened state for fluorescence and photodynamic effects upon an external light trigger. The nanoparticles' photoacoustic and fluorescence imaging properties demonstrate the advantage of the switch. The use of the nanoparticles improves the outcomes of in vivo cancer surgery using preoperative photoacoustic imaging and intraoperative fluorescent visualization/photodynamic therapy of residual tumours to ensure total tumour removal.
The enzyme-triggered self-assembly of peptides has flourished in controlling the self-assembly kinetics and producing nanostructures that are typically inaccessible by conventional self-assembly ...pathways. However, the diffusion and nanoscale chemical gradient of self-assembling peptides generated by the enzyme also significantly affect the outcome of self-assembly, which has not been reported yet. In this work, we demonstrated for the first time a spatiotemporal control of enzyme-triggered peptide self-assembly. By simply adjusting the temperature, we could change both the catalytic activity of the enzyme of phosphatase and their aggregation states. The strategy kinetically controls the production rate of self-assembling peptides and spatially controls their distribution in the system, leading to the formation of nanoparticles at 37 °C and nanofibers at 4 °C. The nanofibers showed ∼10 times higher cellular uptake by 3T3 cells than the nanoparticles, thanks to their higher stability and more ordered structures. Using such spatiotemporal control, we could prepare optimized nanoprobes with low background fluorescence, rapid and high cellular uptake, and high sensitivity. We postulate that this strategy would be very useful in general for preparing self-assembled nanomaterials with controllable morphology and function.
Extracellular vesicles (EVs) are a class of lipid membrane-bound vesicles released by various cells and mediate cell-to-cell communication. By reason of their high physiochemical stability and ...biocompatibility, EVs are considered as novel drug delivery system. An increasing number of studies have indicated that EVs can be modified to enhance their loading efficiency, targeting ability and therapeutic capabilities for cancer therapy. Compared with the tedious process of gene engineering approaches, direct modification of EVs is easier, faster and versatile. This mini review will summarize the prevailing approaches for direct modification of EVs. Additionally, the potential applications of modified EVs in cancer therapy are also discussed, which will help readers gain a better understanding of the technologies and applications in this field.
Immunogenic cell death (ICD) through apoptosis or necroptosis is widely adopted to improve the therapeutic effect in cancer treatment by triggering a specific antitumor immunity. However, the tumor ...resistance to apoptosis/necroptosis seriously impedes the therapeutic effect. Recently, ferroptosis featured with excessive lipid peroxidation is demonstrated capable of bypassing the apoptosis/necroptosis resistance to kill cancer cells. To date, numerous efficient ferroptosis inducers are developed and successfully utilized for sensitizing cancer cells to ferroptosis. Unfortunately, these inducers can hardly generate adequate immunogenicity during induction of ferroptotic cancer cell death, which distinctly attenuates the efficacy of triggering antitumor immune response, therefore leads to unsatisfactory therapeutic effect. Herein, a novel high‐performance photothermal nanoparticle (TPA‐NDTA NP) is designed by exploiting energy via excited‐state intramolecular motion and employed for immensely assisting ferroptosis inducer to evoke highly efficient ICD through ferroptosis pathway. Tumor models with poor immunogenicity are used to demonstrate the tremendously enhanced therapeutic effect endowed by highly enhanced immunogenic ferroptosis in vitro and in vivo by virtue of the NPs. This study sheds new light on a previously unrecognized facet of boosting the immunogenicity of ferroptosis for achieving satisfactory therapeutic effect in cancer therapy.
High‐performance photothermal nanoagents named TPA‐NDTA nanoparticles (NPs) are designed and fabricated by harvesting excited‐state intramolecular motion from strong‐donating molecular rotor using 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐methoxy(polyethylene glycol)‐2000 as an encapsulation matrix. By virtue of the NP‐based photo‐hyperthermia, highly immunogenic ferroptosis is provoked, which leads to a specifically systemic antitumor immunity, therefore benefiting a lot to the ultimate therapeutic effect in ferroptosis‐driven cancer therapy.
Near infrared (NIR) fluorescence imaging (700-900 nm) is a promising technology in preclinical and clinical tumor diagnosis and therapy. The availability of excellent NIR fluorescent contrast agents ...is still the main barrier to implementing this technology. Herein, we report the design and synthesis of two series of NIR fluorescent molecules with long wavelength excitation and aggregation-induced emission (AIE) characteristics by fine-tuning their molecular structures and substituents. Further self-assembly between an amphiphilic block co-polymer and the obtained AIE molecules leads to AIE nanoparticles (AIE NPs), which have absorption maxima at 635 nm and emission maxima between 800 and 815 nm with quantum yields of up to 4.8% in aggregated states.
and
toxicity results demonstrate that the synthesized AIE NPs are biocompatible. Finally, the synthesized AIE NPs have been successfully used for image-guided tumor resection with a high tumor-to-normal tissue signal ratio of 7.2.
Lysosome‐relevant cell death induced by lysosomal membrane permeabilization (LMP) has recently attracted increasing attention. However, nearly no studies show that currently available LMP inducers ...can evoke immunogenic cell death (ICD) or convert immunologically cold tumors to hot. Herein, we report a LMP inducer named TPE‐Py‐pYK(TPP)pY, which can respond to alkaline phosphatase (ALP), leading to formation of nanoassembies along with fluorescence and singlet oxygen turn‐on. TPE‐Py‐pYK(TPP)pY tends to accumulate in ALP‐overexpressed cancer cell lysosomes as well as induce LMP and rupture of lysosomal membranes to massively evoke ICD. Such LMP‐induced ICD effectively converts immunologically cold tumors to hot as evidenced by abundant CD8+ and CD4+ T cells infiltration into the cold tumors. Exposure of ALP‐catalyzed nanoassemblies in cancer cell lysosomes to light further intensifies the processes of LMP, ICD and cold‐to‐hot tumor conversion. This work thus builds a new bridge between lysosome‐relevant cell death and cancer immunotherapy.
We report an alkaline phosphatase (ALP)‐responsive lysosomal membrane permeabilization (LMP) inducer, which can specifically accumulate in cancer cell lysosomes for evoking immunogenic cell death (ICD) and converting immunologically cold tumors into hot tumors.
Display omitted
•TAT peptide-conjugated IR780 (TAT-IR780) was synthesized.•TAT-IR780 and doxorubicin (DOX) self-assembled to form TID nanoparticles.•TID nanoparticles exhibited excellent cellular ...uptake and nucleus-targeting ability.•TID nanoparticles showed synergistic antitumor effects of PTT/PDT and chemotherapy.
Breast cancer is the most common malignant tumor in women. Phototherapy, mainly including photothermal therapy (PTT) and photodynamic therapy (PDT), shows many advantages such as high spatial selectivity, noninvasive nature, and negligible drug resistance for breast cancer treatment. Additionally, recent investigations have shown that nucleus-targeted PTT can kill cancer cells more directly and more efficiently by “burning” cell nuclei closely. In this study, we developed a nucleus-targeting nanoparticle system for combining PTT/PDT and chemotherapy to treat breast cancer. IR780, a near-infrared (NIR) fluorescence dye that has potent anticancer efficacy of PTT and PDT, was firstly conjugated with TAT peptide through substitution reaction between chlorine atom and sulfhydryl group, thus obtained a conjugate TAT-IR780 with notably enhanced water solubility and optical stability. Next, chemotherapeutic drug doxorubicin (DOX) and TAT-IR780 self-assembled in aqueous medium to form TID nanoparticles with a small size of approximately 100 nm. Both in vitro and in vivo, TID nanoparticles showed greatly enhanced PTT/PDT efficiencies as compared with free IR780. Through the mediation of TAT peptide, TID nanoparticles significantly improved the cellular internalization of IR780 in breast cancer cells and delivered it mostly to the perinuclear region. Upon laser irradiation at 785 nm, TID nanoparticles rapidly destroyed the genetic substances and potently induced the apoptosis of breast cancer cells. In the mice bearing breast cancer, intratumoral injection of TID nanoparticles with local laser irradiation realized fluorescence and photothermal imaging-guided combination treatment of nucleus-targeted PTT/PDT and chemotherapy, and achieved significant synergistic effects on breast tumor ablation and recurrence. In summary, this study provides a nucleus-targeting nanoplatform for dual imaging-guided photo-chemotherapy for breast cancer treatment.
Image-guided therapy is one of the most promising strategies for efficiently curing a tumor. Here, a novel nanomaterial with chemiexcited far-red/near-infrared (FR/NIR) emission and singlet oxygen ...(1O2) generation is reported for precise diagnosis and treatment of tumors. Bis2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl oxalate (CPPO) and a specially designed photosensitizer TBD with aggregation-induced FR/NIR emission were co-encapsulated by pluronic F-127 and soybean oil to form C-TBD nanoparticles (C-TBD NPs). These NPs serve as a specific H2O2 probe to precisely track tumors in vivo through chemiluminescence imaging. In addition, effective 1O2 generation by C-TBD NPs in response to tumor H2O2 was observed, which could efficiently induce tumor cell apoptosis and inhibit tumor growth. Both the chemiluminescence response and the therapeutic function were further enhanced when β-phenylethyl isothiocyanate was used to enhance the H2O2 production at the tumor site. Our results prove that C-TBD NPs provide a new strategy for intelligent, accurate, and non-invasive tumor therapy.
Display omitted
•Chemiluminescent nanoparticles with singlet oxygen production are synthesized•The nanoparticles offer selective chemiluminescence imaging of deep tumors•The nanoparticles offer light-source-free photodynamic tumor therapy•The nanoparticles provide a unique platform for precise cancer theranostics
Precise image-guided therapy is key to eradicating tumors in clinical practice. Here, we report a new nanomaterial based on a chemiexcited photosensitizer, which can be specifically activated by H2O2 within the tumor environment to produce far-red/near-infrared luminescence and singlet oxygen. Using such a nanoparticle, primary and metastatic breast tumors can be clearly identified through chemiluminescence imaging with a very high signal-to-noise ratio. Accompanied by the use of an anti-tumor drug, FEITC, the signal of the tumor could be further enhanced as a result of elevated H2O2 production at the tumor site. More importantly, specific tumor killing can be achieved through chemiexcited singlet oxygen production, and the effect of therapy is also increased in the presence of FEITC. Considering the multiple advantages of simultaneous tumor theranostics, our nanoparticle design represents a promising strategy for future clinical tumor therapy.
Organic nanoparticles exhibiting intense FR/NIR chemiluminescence and strong chemiexcited singlet oxygen generation in the presence of H2O2 have been successfully used for selective tumor imaging and therapy. Both tumor chemiluminescent signals and singlet oxygen production can be further enhanced in the presence of an anti-tumor drug, FEITC, which could increase the amount of H2O2 at the tumor site for effective tumor treatment. Our design represents a new strategy for light-source-free image-guided tumor therapy.
Display omitted
Wound healing dressings are increasingly needed clinically due to the large number of skin damage annually. Nitric oxide (NO) plays a key role in promoting wound healing, thus ...biomaterials with NO-releasing property receive increasing attention as ideal wound dressing. In present study, we prepared a novel functional wound dressing by combining electrospun poly(ε-caprolactone) (PCL) nonwoven mat with chitosan-based NO-releasing biomaterials (CS-NO). As-prepared PCL/CS-NO dressing released NO sustainably under the physiological conditions, which was controlled by the catalysis of β-galactosidase. In vivo wound healing characteristics were further evaluated on full-thickness cutaneous wounds in mice. Results showed that PCL/CS-NO wound dressings remarkably accelerated wound healing process through enhancing re-epithelialization and granulation formation and effectively improved the organization of regenerated tissues including epidermal-dermal junction, which could be ascribed to the pro-angiogenesis, immunomodulation, and enhanced collagen synthesis provided by the sustained release of NO. Therefore, PCL/CS-NO may be a promising candidate for wound dressings, especially for the chronic wound caused by the ischemia.
Serious skin damage caused by trauma, surgery, burn or chronic disease has become one of the most serious clinical problems. Therefore, there is an increasing demand for ideal wound dressing that can improve wound healing. Due to the vital role of nitric oxide (NO), we developed a novel functional wound dressing by combining electrospun polycaprolactone (PCL) mat with NO-releasing biomaterial (CS-NO). The sustained release of NO from PCL/CS-NO demonstrated positive effects on wound healing, including pro-angiogenesis, immunomodulation, and enhanced collagen synthesis. Hence, wound healing process was remarkably accelerated and the organization of regenerated tissues was effectively improved as well. Taken together, PCL/CS-NO dressing may be a promising candidate for wound treatment, especially for the chronic wound caused by the ischemia.
PDF
