Inorganic nanoparticles with tunable and diverse properties hold tremendous potential in the field of nanomedicine, while having non‐negligible toxicity concerns in healthy tissues/organs that have resulted in their restricted clinical translation to date. In the past decade, the emergence of biodegradable or clearable inorganic nanoparticles has made it possible to completely solve this long‐standing conundrum. A comprehensive understanding of the design of these inorganic nanoparticles with their metabolic performance in the body is of crucial importance to advance clinical trials and expand their biological applications in disease diagnosis. Here, a diverse variety of biodegradable or clearable inorganic nanoparticles regarding considerations of the size, morphology, surface chemistry, and doping strategy are highlighted. Their pharmacokinetics, pathways of metabolism in the body, and time required for excretion are discussed. Some inorganic materials intrinsically responsive to various conditions in the tumor microenvironment are also introduced. Finally, an overview of the encountered challenges is provided along with an outlook for applying these inorganic nanoparticles toward future clinical translations.

Uncontrolled cancer cell proliferation, insufficient blood flow, and inadequate endogenous oxygen lead to hypoxia in the tumor tissues. Herein, we report a unique type of hypoxiaresponsive human serum albumin (HSA)-based nanosystem (HCHOA) prepared by crosslinking hypoxia-sensitive azobenzene group between photosensitizer chlorin e6 (Ce6)conjugated HSA (HC) and oxaliplatin prodrug-conjugated HSA (HO). The HCHOA nanosystem is stable under normal oxygen partial pressure with the size of 100-150 nm. When exposed to hypoxic tumor microenvironment, the nanosystem could quickly dissociate into ultrasmall HC and HO therapeutic nanoparticles with the diameter smaller than 10 nm, significantly enabling their enhanced intratumoral penetration. After the dissociation, the quenched fluorescence of Ce6 in the produced HC nanoparticles could be recovered for bioimaging. At the same time, the production of singlet oxygen was increased because of the enhancement in the photoactivity of the photosensitizer. On account of these improvements, the combined photodynamic therapy and chemotherapy were realized to display superior antitumor efficacy in vivo. Based on this simple strategy, we were able to achieve the dissociation of 2 hypoxic-responsive nanosystem to enhance the tumor penetration and therapeutic effect.

Development of novel strategies for achieving amorphous ultralong organic phosphorescence (UOP) at room temperature is highly desired. Herein, a simple approach is reported by coassembling small organic molecules with polyvinyl alcohol (PVA) to afford amorphous UOP. These small organic molecules with planar conformation present quenched triplet state emission in an excessive stacking solid state. When coassembling these molecules with PVA, their planar structures are well confined in coassembly films. Such a confined environment leads to restricted molecular rotation and vibration, permitting these molecules to show stable triplet state and generate UOP. In control studies, corresponding structurally distorted molecules are also coassembled with PVA. However, they exhibit very weak or quenched UOP, since distorted structures with molecular rotation and vibration could easily dissipate the excitation energy in dilute film state. By employing this polymer confinement strategy, multicomponent luminescence dyes are further coassembled with PVA for multicolor luminescence displays, providing multicolor, uniform, and flexible luminescence films. This work demonstrates a general strategy of employing small organic molecules to coassemble with PVA to obtain amorphous UOP, which greatly expands the scope of organic molecules for developing simple but useful UOP films.

The therapeutic effect of chemodynamic therapy (CDT) is significantly restricted by the stern reaction conditions and slow reaction rate of the Fenton reaction (pH 3−4). Herein, we report an ultrasmall trimetallic (Pd, Cu, and Fe) alloy nanozyme (PCF-a NEs) possessing dynamic active-site synergism, thus exhibiting a cascade glutathione peroxidase and peroxidase (POD) mimicking activities in circumneutral pH. PCF-a NEs exhibit photothermally augmented POD property and high photothermal conversion efficiency (62%) for synergistic tumor cell apoptosis. In addition, ultrasound can also enhance the mass transfer at active catalytic sites of PCF-a NEs, in turn accelerating Fenton-like reaction for tumor-specific CDT. This work provides a strategy for engineering alloy nanozymes in a bioinspired way for the amplification of intratumor reactive oxygen species in response to external stimuli, demonstrating enhanced efficiency for the inhibition of tumor growth in vitro and in vivo.

Developing molecules with high emission efficiency both in solution and the solid state is still a great challenge, since most organic luminogens are either aggregation‐caused quenching or aggregation‐induced emission molecules. This dilemma was overcome by integrating planar and distorted structures with long alkyl side chains to achieve DAπAD type emitters. A linear diphenyl–diacetylene core and the charge transfer effect ensure considerable planarity of these molecules in the excited state, allowing strong emission in dilute solution (quantum yield up to 98.2 %). On the other hand, intermolecular interactions of two distorted cyanostilbene units restrict molecular vibration and rotation, and long alkyl chains reduce the quenching effect of the π–π stacking to the excimer, eventually leading to strong emission in the solid state (quantum yield up to 60.7 %).

Therapeutic efficacy of synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) is limited by complex conjugation chemistry, absorption wavelength mismatch and inadequate biodegradability of the PDT-PTT agents. Herein, we designed biocompatible copper sulfide nanodot anchored folic acid-modified black phosphorus nanosheets (BP-CuS-FA) to overcome these limitations, consequently enhancing the therapeutic efficiency of PDT-PTT. In vitro and in vivo assays reveal good biocompatibility and commendable tumor inhibition efficacy of the BP-CuS-FA nanoconjugate owing to synergistic PTT-PDT mediated by near-infrared laser irradiation. Importantly, folic acid unit could target folate receptor overexpressed cancer cells, leading to enhanced cellular uptake of BP-CuS-FA. BP-CuS-FA also exhibits significant contrast 2 effect for photoacoustic imaging, permitting its in vivo tracking. The photodegradable character of BP-CuS-FA is associated with better renal clearance after the antitumor therapy in vivo. The present research may facilitate further development on straightforward approaches for targeted and imaging-guided synergistic PDT-PTT of cancer.

Clinical translation of artesunate (ATS) as a potent antitumor drug has been obstructed by its rapid degradation and low bioavailability. Herein, we report the development of an ATS nanomedicine through the self‐assembly with Mn[Co(CN)6]2/3□1/3 metal–organic frameworks (MOFs) that have hidden missing linkers. The defects in MOFs originating from the missing linkers play a key role in increasing the biological stability and tumor accumulation of ATS. Chlorin e6 (Ce6) and ATS can be co‐loaded into MOFs for a synergistic antitumor efficacy. In the presence of intracellular HCO3−, Mn2+ acts as an efficient catalyst to promote the bicarbonate‐activated H2O2 system which oxidizes ATS to generate reactive oxygen species and induce oxidative death to cancer cells. The released [CoIII(CN)6] linker undergoes a redox reaction with intracellular glutathione to prevent the scavenging ability of reactive oxygen species, contributing to synergistic chemodynamic therapy of ATS and photodynamic therapy of Ce6. Thus, defect‐engineered MOFs with hidden missing linkers hold great promise in advancing the practical use of ATS as an antitumor medicine.

In article number https://doi.org/10.1002/adfm.201807243, Yanli Zhao and co‐workers develop a strategy to confine planar small organic molecules using polyvinyl alcohol (PVA), where the molecular rotation and vibration of these molecules are restricted in the coassembly, achieving ultralong room temperature phosphorescence. Thus, coassembling multicomponent luminescence dyes with PVA leads to multicolor and flexible luminescence films for display applications.