Hollow nanostructures have attracted significant research interest in drug delivery systems due to their high capacities for drug loading and unique physicochemical properties, showing great potential in specific biomedical applications. Herein, hollow porphyrinic metal–organic framework (H-PMOF) nanoparticles with a mesoporous spherical shell have been fabricated via a facile self-sacrificial ZIF-8 nanoparticle template strategy. The H-PMOF nanoplatform not only demonstrates a greatly enhanced photodynamic therapy efficacy compared with nonhollow porphyrinic MOF nanoparticles but also can be used as a superior drug carrier to co-load doxorubicin (DOX) and indocyanine green (ICG) with an ultrahigh drug-loading capacity of 635%. Furthermore, cancer cell membrane camouflage of the (DOX and ICG)@H-PMOF composite nanoparticles affords a biomimetic nanoplatform, that is, (DOX and ICG)@H-PMOF@mem (DIHPm for short), with an outstanding homologous tumor-targeting and immune-escaping ability. Interestingly, DIHPm shows both pH-controlled and near-infrared laser-triggered DOX release. Both in vitro and in vivo studies of DIHPm demonstrate an excellent imaging-guided synergistic photodynamic/photothermal/chemotherapy anticancer activity with negligible systemic toxicity. The development of the high-performance H-PMOF nanoplatform provides new insights into the design of MOF-based multifunctional nanomedicines for combination cancer therapy and precise theranostics.

Six homo-or heteroleptic tricationic Ir(R 1-tpy)(R 2-tpy) 3+ complexes (Ir1-Ir6, R 1 /R 2 = Ph, 4′-N(CH 3) 2 Ph, pyren-1-yl, or 4′-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}Ph, tpy = 2,2';6',2"terpyridine) were synthesized and tested for photodynamic therapy (PDT) effects. The ground-and excited-state characteristics of these complexes were studied systematically via spectroscopic methods and quantum chemistry calculations. All complexes possessed intraligand charge transfer (1 ILCT) / metal-to-ligand charge transfer (1 MLCT) dominated transition(s) in their low-energy absorption bands, which red-shifted with the increased electron-releasing strength of the R 1 /R 2 substituent. Five of the complexes exhibited ligand-centered 3 π,π*/ 3 ILCT/ 3 MLCT emission. With a stronger electron-releasing R 1 /R 2 substituent, the degree of charge transfer contribution increased, leading to a decrease of the emission quantum yield. When the 4′-N(CH 3) 2 Ph substituent was introduced on both tpy ligands, the emission of Ir3 was completely quenched. Our *

Immune checkpoint blockade (ICB) is an attractive option in cancer therapy, but its efficacy is still less than expected due to the transient and incomplete blocking and the low responsiveness. Herein, an unprecedented programmable unlocking nano-matryoshka-CRISPR system (PUN) targeting programmed cell death ligand 1 (PD-L1) and protein tyrosine phosphatase N2 (PTPN2) is fabricated for permanent and complete and highly responsive immunotherapy. While PUN is inert at normal physiological conditions, enzyme-abundant tumor microenvironment and preternatural intracellular oxidative stress sequentially trigger programmable unlocking of PUN to realize a nano-matryoshka-like release of CRISPR/Cas9. The successful nucleus localization of CRISPR/Cas9 ensures the highly efficient disruption of PD-L1 and PTPN2 to unleash cascade amplified adaptive immune response via revoking the immune checkpoint effect. PD-L1 downregulation in tumor cells not only disrupts PD-1/PD-L1 interaction to attenuate the immunosurveillance evasion but also spurs potent immune T cell responses to enhance adaptive immunity. Synchronously, inhibition of JAK/STAT pathway is relieved by deleting PTPN2, which promotes tumor susceptibility to CD8 + T cells depending on IFN-, thus further amplifying adaptive immune responses. Combining these advances together, PUN exhibits optimal antitumor efficiency and long-term immune memory with negligible toxicity, which provides a promising alternative to current ICB therapy.

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PB attenuates neurological deficits and BBB disruption in a rat model of cerebral ischemia, and the neuroprotection of PB is associated with activation of NF-E2-related factor pathway.