为了解决光动力疗法（PDT）中的靶向特异性和光传输到深层组织的问题，我们报告了一种癌细胞靶向光敏剂，其使用具有高靶向特异性和有效光传输到深层组织的光蛋白结合上转换纳米颗粒（UCNPs）。该核壳结构UCNPs低内部能量返转，通过与包含光敏剂（KillerRed; KR）和癌细胞靶向引导肽（LP）的重组蛋白偶联。在近红外（NIR）照射条件下，UCNP-KR-LP通过NIR到绿光转换产生超氧离子自由基，并通过受体介导的细胞黏附显著特异性靶向癌细胞。因此，该光敏化过程促进了在过表达整合素β 1（ITGB1）受体的癌细胞系（MCF-7，MDA-MB-231和U-87MG）中的快速细胞死亡，而在ITGB1表达降低的细胞系（SK-BR-3）和非侵袭性正常乳腺细胞系（MCF-10A）中未观察到细胞死亡现象。与绿光照射相比，近红外光照射在位于猪皮肤组织下的癌细胞以及体内肿瘤异种移植小鼠模型中均显示出显著的PDT效果。该发现表明设计的纳米复合材料在感测和靶向治疗各种深层肿瘤方面具有重要意义。 © 2023. BioMed Central Ltd., part of Springer Nature.

To resolve the problem of target specificity and light transmission to deep-seated tissues in photodynamic therapy (PDT), we report a cancer cell-targeted photosensitizer using photoprotein-conjugated upconversion nanoparticles (UCNPs) with high target specificity and efficient light transmission to deep tissues. Core-shell UCNPs with low internal energy back transfer were conjugated with recombinant proteins that consists of a photosensitizer (KillerRed; KR) and a cancer cell-targeted lead peptide (LP). Under near infrared (NIR)-irradiating condition, the UCNP-KR-LP generated superoxide anion radicals as reactive oxygen species via NIR-to-green light conversion and exhibited excellent specificity to target cancer cells through receptor-mediated cell adhesion. Consequently, this photosensitizing process facilitated rapid cell death in cancer cell lines (MCF-7, MDA-MB-231, and U-87MG) overexpressing integrin beta 1 (ITGB1) receptors but not in a cell line (SK-BR-3) with reduced ITGB1 expression and a non-invasive normal breast cell line (MCF-10A). In contrast to green light irradiation, NIR light irradiation exhibited significant PDT efficacy in cancer cells located beneath porcine skin tissues up to a depth of 10 mm, as well as in vivo tumor xenograft mouse models. This finding suggests that the designed nanocomposite is useful for sensing and targeting various deep-seated tumors.© 2023. BioMed Central Ltd., part of Springer Nature.