The clinical translation of tumor hypoxia intervention modalities still falls short of expectation, restricted by poor biocompatibility of oxygen-carrying materials, unsatisfactory oxygen loading performance, and abnormally high cellular oxygen consumption-caused insufficient hypoxia relief. Herein, a carrier-free oxygen nano-tank based on modular fluorination prodrug design and co-assembly nanotechnology is elaborately exploited, which is facilely fabricated through the molecular nanoassembly of a fluorinated prodrug (FSSP) of pyropheophorbide a (PPa) and an oxygen consumption inhibitor (atovaquone, ATO). The nano-tank adeptly achieves sufficient oxygen enrichment while simultaneously suppressing oxygen consumption within tumors for complete tumor hypoxia alleviation. Significant, the fluorination module in FSSP not only confers favorable co-assemblage of FSSP and ATO, but also empowers the nanoassembly to readily carry oxygen. As expected, it displays excellent oxygen carrying capacity, favorable pharmacokinetics, on-demand laser-triggerable ATO release, closed-loop tumor hypoxia relief, and significant enhancement to PPa-mediated PDT in vitro and in vivo. This study provides a novel nanotherapeutic paradigm for tumor hypoxia intervention-enhanced cancer therapy.

Photodynamic therapy (PDT) has been extensively investigated for cancer treatment by virtue of singlet oxygen-induced oxidative damage to tumors. Nevertheless, the therapeutic efficiency of PDT is still limited by the low singlet oxygen yield attributed to the improper irradiation duration and the tumor hypoxic microenvironment. To tackle these challenges, we elaborately design a theranostic oxygen nano-economizer to self-report the optimal irradiation duration and alleviate tumor hypoxia simultaneously, which is engineered by fluorescent 9,10-anthracenyl bis (benzoic acid) (DPA)-MOF, tetrakis (4-carboxyphenyl) porphyrin (TCPP), triphenyl phosphine (TPP) and redox-responsive lipid-PEG (DSPE-SS-PEG2k). Upon laser irradiation, the fluorescence of DPA-MOF could be quenched, thereby self-reporting the optimal irradiation duration for sufficient PDT. The decoration of DSPE-SS-PEG2k and TPP endows the theranostic oxygen nano-economizer with a tumor-specific response and mitochondrial targeting capability, respectively. Notably, singlet oxygen generated from TCPP reduces oxygen consumption by disrupting the entire oxidative phosphorylation (OXPHOS) pathway in the mitochondria of tumor cells, further improving the level of singlet oxygen in a self-facilitated manner for hypoxia alleviation-potentiated PDT. As expected, such a self-reported and self-facilitated theranostic oxygen nano-economizer exhibits potent antitumor activity in the 4T1 tumor-bearing mouse model. This study offers a theranostic paradigm for precise and hypoxia alleviation-potentiated cancer therapy. A self-reported and self-facilitated theranostic oxygen nano-economizer (PTTD NPs) for precise photodynamic therapy (PDT) is developed. Under self-reported optimal laser duration, PTTD NPs could alleviate tumor hypoxia for self-facilitating PDT.

Platelets, as abundant corpuscles in the blood, are extensively involved in normal physiological processes and disease occurrence. Recently, remarkable progress in platelet based nanotherapeutics has been made, especially with the burgeoning fields of biotechnology and nanomedicine. Herein, we aim to provide an overview on platelet-inspired nano therapeutics for biomedical applications. First, the recent trends of biomimetic platelet-inspired nanotherapeutics are outlined, mainly including platelet membrane-camouflaged nanosystems, platelets loading with nanoparticles and platelet-mimicking nanocarriers. Then, the emerging nanotherapeutics for functional modulation of platelet aggregation, activation, and inhibition are discussed. Subsequently, platelet derivative-based nanotherapeutics are presented, including platelet extracellular vesicles and platelet polyphosphates. Finally, the clinical application prospects of these emerging nanotherapeutics are highlighted, with particular emphasis on their rationale, advantages, and challenges.

Photodynamic therapy (PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species (ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway (UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib (BTZ, a proteasome inhibitor) and pyropheophorbide a (PPa) for proteasome inhibition-mediated PDT sensitization. The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment, good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment.

Photodynamic therapy (PDT) has been extensively explored for cancer treatment. There is growing evidence showing that oxidative DNA damage caused by the vast accumulation of reactive oxygen species (ROS) in tumor cells plays a dominant role in accelerating cell apoptosis. Nevertheless, the repair pathways of aberrant DNA in tumor cells help reduce and reverse such damage. Thus, a precise combination of photodynamic photosensitizers and DNA repair inhibitors is expected to significantly augment the PDT efficacy. But it remains challenging to achieve accurate co-delivery of two drugs into the target sites. Herein, an ingenious dual-drug assembly modality is developed to precisely engineer a novel co-delivery nanomedicine. For proof-of-concept, a carrier-free hybrid nanoassembly of etoposide (VP-16) and pyropheophorbide a (PPa) is elaborately fabricated for multimodal DNA damage-mediated synergistic cancer therapy. Generally, this study exhibits a facile and practical dual-drug co-assembly engineering strategy, constructs an efficient and versatile co-delivery nanoplatform, and enables significant combination anticancer efficacy in vitro and in vivo. Such a dual-drug hybrid nanoassembly has the potential to be utilized as a promising nanomedicine for clinical multimodal cancer therapy.

Thrombotic cardio-cerebrovascular diseases seriously threaten human health. Currently, conventional thrombolytic treatments are challenged by the low utilization, inferior thrombus penetration, and high off-target bleeding risks of most thrombolytic drugs, resulting in unsatisfactory treatment outcomes. Herein, it is proposed that these challenges can be overcome by precisely integrating the conventional thrombolytic strategy with photothermal therapy. After co-assembly engineering optimization, a fibrin-targeting peptide-decorated nanoassembly of DiR (a photothermal probe) and ticagrelor (TGL, an antiplatelet drug) is prepared for thrombus-homing delivery, abbreviated as FT-DT NPs. The elaborately engineered nanoassembly shows multiple advantages, including simple preparation with high drug co-loading capacity, synchronous delivery of two drugs with long systemic circulation, thrombus-targeted accumulation with self-indicating function, as well as photothermal-potentiated thrombus penetration and thrombolysis with high therapeutic efficacy. As expected, FT-DT NPs not only show bright fluorescence signals in the embolized vessels, but also perform photothermal/antiplatelet synergistic thrombolysis in vivo. This study offers a simple and versatile co-delivery nanoplatform for imaging-guided photothermal/antiplatelet dual-modality thrombolysis.

Tumor metastases, that is, the development of secondary tumors in organs distant from the primary tumor, and their treatment remain a serious problem in cancer therapy. The unique challenges for tracking and treating tumor metastases lie in the small size, high heterogeneity, and wide dispersion to distant organs of metastases. Recently, nanomedicines, with the capacity to precisely deliver therapeutic agents to both primary and secondary tumors, have demonstrated many potential benefits for metastatic cancer theranostics. Given the remarkable progression in emerging nanotherapeutics for antimetastatic treatment, it is timely to summarize the latest advances in this field. This review highlights the rationale, advantages, and challenges for integrating biomedical nanotechnology with cancer biology to develop antimetastatic nanotherapeutics.

Thrombus causes insufficient blood flow and ischemia damages to brain and heart, leading to life-threatening cardio-cerebrovascular diseases. Development of efficient antithrombotic strategies has long been a high priority, owing to the high morbidity and mortality of thrombotic diseases. With the rapid development of biomedical nanotechnology in diagnosis and treatment of thrombotic disorder, remarkable progresses have been made in antithrombotic nanomedicines in recent years. Herein, we outline the recent advances in this field at the intersection of thrombus theranostics and biomedical nanotechnology. First, thrombus diagnosis techniques based on biomedical nanotechnology are presented. Then, emerging antithrombotic nanotherapeutics are overviewed, including thrombus-targeting strategies, thrombus stimuli-responsive nanosystems and phase transition-driven nanotherapeutics. Furthermore, multifunctional nanosystems for combination theranostics of thrombotic diseases are discussed. Finally, the design considerations, advantages and challenges of these biomedical nanotechnology-driven therapeutics in clinical translation are highlighted.

目的 对比某国内企业生产的三批羟丙基纤维素L-11(hydroxypropyl cellulose L-11,HPC L-11)表面形貌、粉体学性质和部分功能性指标,分析和研究辅料HPC L-11的批间重现性及其可能对制剂性质的影响.方法 采用扫描电子显微镜、差示扫描量热法、热重分析法、比表面积法、静态液滴法等测定HPC L-11的表面形貌、粉体学性质等.结果 在各研究项目中三批次辅料的结果是一致的.结论 提示国产辅料的质量及批间重现性有所提升.该研究方法及结果对辅料和制剂生产工艺及质量平行稳定有重要意义,对制剂性质、质量和疗效的一致性评价工作具有参考价值.