Nanjing University of Posts & Telecommunications

Tumor heterogeneity disrupts the consistent expression of target markers, leading to inefficient tumor targeting and contributing to drug resistance and relapse. Therefore, seeking a more universal target is crucial for enhancing drug enrichment in tumors. In this study, we propose a self-amplifying tumor-targeting strategy that leverages externalized phosphatidylserine (PtdSer) on apoptotic cells as a universal target. The system is composed of a Red Blood Cell-Liposome hybrid membrane camouflaged Mn-Ce6 nanocomplex, which is further modified with a PtdSer aptamer (MC@RL/Apt). MC@RL/Apt demonstrates prolonged circulation time and enhanced tumor accumulation, capable of inducing cancer cell apoptosis and PtdSer externalization under 660 nm light irradiation. The externalized PtdSer is then recognized by the PtdSer aptamer, which recruits additional MC@RL/Apt to the tumor site, facilitating a self-amplified tumor accumulation effect. In vitro studies show that MC@RL/Apt acted as an efferocytosis inhibitor, suppressing macrophage phagocytosis of apoptotic cells and promoting macrophage polarization toward the pro-inflammatory M1 phenotype. Compared to non-functionalized MC@RL, intravenous administration of MC@RL/Apt increases tumor accumulation by 1.46-fold under 660 nm light irradiation. As a result, treatment with MC@RL/Apt effectively suppressed tumor growth and induced robust antitumor immune responses. This work highlights a self-amplifying tumor-targeting strategy that leverages externalized PtdSer on apoptotic cells as a target to enhance tumor-specific drug delivery, while simultaneously inhibiting PtdSer-mediated macrophage engulfment, offering a promising approach for improving cancer therapy outcomes.

Second near-infrared photothermal therapy (NIR-II-PTT) has emerged as a promising therapeutic modality in diverse medical aspects. In particular, J-aggregate is a potential strategy to develop high-performance NIR-II-PTT materials, however, it suffers from specific molecular skeletons and complex control conditions. Herein, we presented a simply electron-donor planar extension strategy to develop donor-acceptor-donor (D-A-D) type small molecules with charge-transfer (CT)-mediated J-aggregation for NIR-II PTT. By integrating ring-fused thiophene units in a benzo[1,2-'c:4,5-c']bis[1,2,5]thiadiazole (BBTDT) scaffold, we enabled tunable electrostatic and π-π interactions, promoting CT-mediated J-aggregate formation. The resulting BDTT nanoparticles showed an impressive light-harvesting capability (ɛ₁₀₆₄) of 2.92 × 10⁴ M^-1 cm^-1 under 1064 nm excitation, yielding an exceptional photothermal performance (ɛ₁₀₆₄ × PCE = 1.99 × 10⁴), which surpasses those of reported D-A-D type NIR-II-absorbing small molecules. This outstanding NIR-II photothermal property induced sufficient immunogenic cell death and amplified the final ablation of deep-seated tumor in conjunction with programmed cell death protein 1 (PD-1). Meanwhile, the fabricated BDTT nanoparticles also facilitated hyperthermia-triggered bacterial death. Together, this study provides valuable insights into developing NIR-II-absorbing J-aggregates based on D-A-D type small molecules, and offers critical potentials to treat malignant tumors and prevents postsurgical infections.

The characterization of biological macromolecules such as proteins and their interactions are crucial to understanding biological processes, disease diagnosis, and drug design. With the rapid development of proteomics, nanopore technology has emerged potentially as a single-molecule profile for huge amounts of peptides and proteins defined in the biological system, particularly for protein sequencing. This review focuses on recent advances in nanopore sensing of proteins and peptides, involving protein dynamic interactions, protein fingerprinting, and protein sequencing. These progresses will provide new perspectives to decipher the mechanisms of protein structure and function, and serve much more possible applications.