Phase change material based H2O2 self-supply nanoparticles for enhanced thermal responsive chemodynamic tumor therapy.
Summary Phototheranostics integrates deep-tissue imaging with phototherapy (containing photothermal therapy and photodynamic therapy), holding great promise in early diagnosis and precision treatment of cancers. Recently, second near-infrared (NIR-II) fluorescence imaging exhibits the merits of high accuracy and specificity, as well as real-time detection. Among the NIR-II fluorophores, organic small molecular fluorophores have shown superior properties in the biocompatibility, variable structure, and tunable emission wavelength than the inorganic NIR-II materials. What's more, some small molecular fluorophores also display excellent cytotoxicity when illuminated with the NIR laser. This review summarizes the progress of small molecular NIR-II fluorophores with different central cores for cancer phototheranostics in the past few years, focusing on the molecular structures and phototheranostic performances. Furthermore, challenges and prospects of future development toward clinical translation are discussed.
Hypoxia severely impedes photodynamic therapy (PDT) efficiency. Worse still, considerable tumor metastasis will occur after PDT. Herein, an organic superoxide radical (O2∙−) nano‐photogenerator as a highly effcient type I photosensitizer with robust vascular‐disrupting efficiency to combat these thorny issues is designed. Boron difluoride dipyrromethene (BODIPY)‐vadimezan conjugate (BDPVDA) is synthesized and enwrapped in electron‐rich polymer‐brushes methoxy‐poly(ethylene glycol)‐b‐poly(2‐(diisopropylamino) ethyl methacrylate) (mPEG‐ PPDA) to afford nanosized hydrophilic type I photosensitizer (PBV NPs). Owing to outstanding core–shell intermolecular electron transfer between BDPVDA and mPEG‐PPDA, remarkable O2∙− can be produced by PBV NPs under near‐infrared irradiation even in severe hypoxic environment (2% O2), thus to accomplish effective hypoxic‐tumor elimination. Simultaneously, the efficient ester‐bond hydrolysis of BDPVDA in the acidic tumor microenvironment allows vadimezan release from PBV NPs to disrupt vasculature, facilitating the shut‐down of metastatic pathways. As a result, PBV NPs will not only be powerful in resolving the paradox between traditional type II PDT and hypoxia, but also successfully prevent tumor metastasis after type I PDT treatment (no secondary‐tumors found in 70 days and 100% survival rate), enabling enhancement of existing hypoxic‐and‐metastatic tumor treatment.
Tumor hypoxia severely impedes the therapeutic efficacy of type II photodynamic therapy (PDT) depending on singlet oxygen (1O2) generation. To combat hypoxic tumors, herein, a new approach is devised to boost superoxide radical (O2•−) photogeneration for type I PDT. Heavy atoms are introduced onto aza‐BODIPY molecules (iodine substituted butoxy‐aza‐BODIPY, IBAB) to promote their intersystem‐crossing (ISC) ability. Meanwhile, methoxy‐poly(ethylene glycol)‐b‐poly(2‐(diisopropylamino) ethyl methacrylate) (mPEG‐PPDA) with enhanced electron‐donating efficiency is employed as a coating matrix to encapsulate IBAB, thereby obtaining amphiphilic aza‐BODIPY nanoplatforms (PPIAB NPs). Under irradiation, triplet‐state IBAB in PPIAB NPs is efficiently generated from singlet state favored by the elevated ISC ability. The electron‐rich environment provided by mPEG‐PPDA can donate triplet‐state IBAB with one electron to form charge‐separated‐state IBAB, which in turn transfers electron to O2 for O2•− production. Significantly, owing to recyclable O2 generated by disproportionation or Harber–Weiss/Fenton reaction, prominent O2•− is generated by PPIAB NPs even in a severe hypoxic environment (2% O2), enabling superior therapeutic efficacy (96.2% tumor‐inhibition rate) over NPs not following this strategy. Thus, the proof‐of‐concept design of ISC‐enhanced and electron‐rich polymer encapsulating PPIAB NPs illuminates the path to preparing O2•− photogenerator for hypoxic cancer treatment.
Precision oncotherapy can remove tumors without causing any apparent iatrogenic damage or irreversible side effects to normal tissues. Second nearinfrared (NIR-II) nanotheranostics can simultaneously perform diagnostic and therapeutic modalities in a single nanoplatform, which exhibits prominent perspectives in tumor precision treatment. Among all NIR-II nanotheranostics, NIR-II organic nanotheranostics have shown an exceptional promise for translation in clinical tumor treatment than NIR-II inorganic nanotheranostics in virtue of their good biocompatibility, excellent reproducibility, desirable excretion, and high biosafety. In this review, recent progress of NIR-II organic nanotheranostics with the integration of tumor diagnosis and therapy is systematically summarized, focusing on the theranostic modes and performances. Furthermore, the current status quo, problems, and challenges are discussed, aiming to provide a certain guiding significance for the future development of NIR-II organic nanotheranostics for precision oncotherapy.
ObjectivesTo investigate the validity of data extraction in systematic reviews of adverse events, the effect of data extraction errors on the results, and to develop a classification framework for data extraction errors to support further methodological research.DesignReproducibility study.Data sourcesPubMed was searched for eligible systematic reviews published between 1 January 2015 and 1 January 2020. Metadata from the randomised controlled trials were extracted from the systematic reviews by four authors. The original data sources (eg, full text and ClinicalTrials.gov) were then referred to by the same authors to reproduce the data used in these meta-analyses.Eligibility criteria for selecting studiesSystematic reviews were included when based on randomised controlled trials for healthcare interventions that reported safety as the exclusive outcome, with at least one pair meta-analysis that included five or more randomised controlled trials and with a 2×2 table of data for event counts and sample sizes in intervention and control arms available for each trial in the meta-analysis.Main outcome measuresThe primary outcome was data extraction errors summarised at three levels: study level, meta-analysis level, and systematic review level. The potential effect of such errors on the results was further investigated.Results201 systematic reviews and 829 pairwise meta-analyses involving 10 386 randomised controlled trials were included. Data extraction could not be reproduced in 1762 (17.0%) of 10 386 trials. In 554 (66.8%) of 829 meta-analyses, at least one randomised controlled trial had data extraction errors; 171 (85.1%) of 201 systematic reviews had at least one meta-analysis with data extraction errors. The most common types of data extraction errors were numerical errors (49.2%, 867/1762) and ambiguous errors (29.9%, 526/1762), mainly caused by ambiguous definitions of the outcomes. These categories were followed by three others: zero assumption errors, misidentification, and mismatching errors. The impact of these errors were analysed on 288 meta-analyses. Data extraction errors led to 10 (3.5%) of 288 meta-analyses changing the direction of the effect and 19 (6.6%) of 288 meta-analyses changing the significance of the P value. Meta-analyses that had two or more different types of errors were more susceptible to these changes than those with only one type of error (for moderate changes, 11 (28.2%) of 39 v 26 (10.4%) 249, P=0.002; for large changes, 5 (12.8%) of 39 v 8 (3.2%) of 249, P=0.01).ConclusionSystematic reviews of adverse events potentially have serious issues in terms of the reproducibility of the data extraction, and these errors can mislead the conclusions. Implementation guidelines are urgently required to help authors of future systematic reviews improve the validity of data extraction.
Despite the clinical potential, photodynamic therapy (PDT) relying on singlet oxygen (1O2) generation is severely limited by tumor hypoxia and endosomal entrapment. Herein, a proton‐driven transformable 1O2‐nanotrap (ANBDP NPs) with endosomal escape capability is presented to improve hypoxic tumor PDT. In the acidic endosomal environment, the protonated 1O2‐nanotrap ruptures endosomal membranes via a “proton‐sponge” like effect and undergoes a drastic morphology‐and‐size change from nanocubes (≈94.1 nm in length) to nanospheres (≈12.3 nm in diameter). Simultaneously, anthracenyl boron dipyrromethene‐derived photosensitizer (ANBDP) in nanospheres transforms to its protonated form (ANBDPH) and switches off its charge‐transfer state to achieve amplified 1O2 photogeneration capability. Upon 730 nm photoirradiation, ANBDPH prominently produces 1O2 and traps generated‐1O2 in the anthracene group to form endoperoxide (ANOBDPH). Benefitting from the hypoxia‐tolerant 1O2‐release property of ANOBDPH in the dark, the 1O2‐nanotrap brings about sustained therapeutic effect without further continuous irradiation, thereby achieving remarkable antitumor performance.
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