RESUMO
Ca2+ , a ubiquitous but nuanced modulator of cellular physiology, is meticulously controlled intracellularly. However, intracellular Ca2+ regulation, such as mitochondrial Ca2+ buffering capacity, can be disrupted by 1 O2 . Thus, the intracellular Ca2+ overload, which is recognized as one of the important cell pro-death factors, can be logically achieved by the synergism of 1 O2 with exogenous Ca2+ delivery. Reported herein is a nanoscale covalent organic framework (NCOF)-based nanoagent, namely CaCO3 @COF-BODIPY-2I@GAG (4), which is embedded with CaCO3 nanoparticle (NP) and surface-decorated with BODIPY-2I as photosensitizer (PS) and glycosaminoglycan (GAG) targeting agent for CD44 receptors on digestive tract tumor cells. Under illumination, the light-triggered 1 O2 not only kills the tumor cells directly, but also leads to their mitochondrial dysfunction and Ca2+ overload. An enhanced antitumor efficiency is achieved via photodynamic therapy (PDT) and Ca2+ overload synergistic therapy.
Assuntos
Antineoplásicos/uso terapêutico , Compostos de Boro/química , Carbonato de Cálcio/química , Neoplasias/tratamento farmacológico , Animais , Sinalização do Cálcio , Linhagem Celular Tumoral , Sinergismo Farmacológico , Glicosilação , Humanos , Camundongos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Fotoquimioterapia , Análise Espectral/métodos , Difração de Raios X , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Synergistic phototherapy combining photodynamic therapy (PDT) and photothermal therapy (PTT) based on near-infrared (NIR) dyes using a single light source offers the opportunity to treat diseases at deep locations. In this study, we reported human serum albumin (HSA)-involving tetra(butylamino)phthalocyanine (Pc)-based nanomaterials of HSA-α-Pc and HSA-ß-Pc as highly efficient dual-phototherapy agents, namely 1(4),8(11),15(18),22(25)-tetra(butylamino)phthalocyanine (α-Pc) and 2(3),9(10),16(17),23(24)-tetra(butylamino)phthalocyanine (ß-Pc). Both HSA-α-Pc and HSA-ß-Pc showed excellent photothermal effects under a single NIR (808 nm) laser irradiation due to the S 1 fluorescence emission quenching of Pcs. Compared to HSA-ß-Pc, HSA-α-Pc exhibited better singlet oxygen generation ability and its highly efficient PDT/PTT dual-phototherapy was also well evidenced via in vitro and vivo experiments under a single 808 nm laser irradiation. Overall, this approach would be viable for the fabrication of more new Pc-based metal-free nano agents for PDT/PTT synergistic phototherapy upon a single NIR light source.