Cancer remains a major threat to global public health, highlighting the urgent need for precise and effective treatment strategies. Photothermal therapy (PTT) has gained increasing attention as a promising alternative owing to its non-invasiveness, deep tissue penetration, and oxygen-independent mechanism. However, the development of high-performance organic photothermal agents (PTAs) with pronounced near-infrared absorption, high photothermal conversion efficiency (PCE), and good photostability remains challenging. Herein, we propose a synergistic strategy combining π-bridge and donor engineering to design a series of aggregation-induced emission (AIE)-active small-molecule photosensitizers. Experimental and theoretical analyses reveal that stepwise introduction of a planar thiophene π-bridge and methoxy donor groups systematically regulates the excited-state energy dissipation pathways, enabling a continuous modulation from photodynamic therapy (IsoTPA), through balanced synergistic PDT/PTT (IsoTHTPA, PCE = 57.2%), to highly efficient PTT (IsoTHTO, PCE = 64.3%), which reveals the fundamental competitive interplay between intersystem crossing and non-radiative decay. Encapsulated into nanoparticles, IsoTHTO NPs demonstrate efficient photothermal ablation of 4T1 tumor cells and significant tumor growth inhibition under 660 nm laser irradiation both in vitro and in vivo. This work presents a reasonable molecular design approach for tunable access to PDT, synergistic PDT/PTT, and PTT modalities from a single molecular platform for cancer phototheranostics.
Yin Li, Dong He, Lu Liu et al.· Advanced Healthcare Material...· 0 citations
Efficient delivery of large, negatively charged self-amplifying RNA (saRNA) into dendritic cells (DCs) is critical for next-generation cancer vaccines. However, this remains challenging due to the high sensitivity of DCs to chemical carriers and high-voltage electroporation. In this study, an integrated nanopore-electroporation (NEP) microdevice was developed by combining 200 nm track-etched polycarbonate membrane, bidirectional PDMS microfluidic channels, and Pt/ITO electrodes to localize the electric field and induce membrane permeabilization at low voltage (≤30 V). Multiphysics simulations revealed that 200 nm nanopores concentrated the electric field at the cell–membrane interface, generating transmembrane potentials exceeding 3 V. Using DC2.4, the NEP system achieved 75% propidium iodide (PI) uptake at 25 V with 90% viability, confirming controllable nanoscale perforation. Direct delivery of GFP-encoding saRNA achieved approximately 50% transfection efficiency with sustained protein expression for more than 96 h, significantly outperforming mRNA at an equal dose. Long-term viability (>85% at 96 h) and negligible cytotoxicity demonstrated the excellent biocompatibility of the device. This reagent-minimal, modular NEP platform thus provided a high-efficiency, low-toxicity route for saRNA delivery into hard-to-transfect immune cells, offering a versatile engineering framework for DC-based cancer immunotherapy, RNA vaccine development, and broader cell gene-modification applications.
Bowen Zhang, Yijing Cai, Caiguanxi Deng et al.· Microsystems & Nanoengineeri...· 0 citations
