Department of Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong SAR.
Nanoscale. 2018 Mar 1;10(9):4432-4441. doi: 10.1039/c7nr06874c.
Upconversion nanoparticles (UCNPs) are widely utilized for photodynamic therapy (PDT) due to their specific upconverting luminescence that utilizes near infrared (NIR) light to excite photosensitizers (PSs) for PDT. The efficiency of UCNP-based PDT will be improved if the cancer-targeting property of nanomedicine is enhanced. Herein, we employed the pH low insertion peptide (pHLIP), a cancer-targeting moiety, to functionalize an 808 nm excited UCNP-based nanoplatform that has a minimized over-heating effect to perform PDT. pHLIP can bring cargo specifically into cancer cells under an acidic environment, realizing the effective active-targeting abilities to cancer cells or tumor due to acidosis. The pHLIP-functionalized nanoplatform was assembled and well characterized. The nanoplatform shows an efficient NIR-irradiated PDT effect in cancer cells, especially under a slightly acidic condition that mimics the tumor microenvironment, and this effectiveness is attributed to the targeting properties of pHLIP to cancer cells under acidic conditions that favor the entry of the nanoplatform. Furthermore, the pHLIP-functionalized nanoplatform shows a favorable safety profile in mice with a high maximum tolerated dose (MTD), which may broaden the availability of administration in vivo. The efficient in vivo antitumor activity is achieved through intratumor injection of the nanoplatform followed by NIR irradiation on the breast tumor. The nanoparticles are largely accumulated in the tumor site, revealing the excellent tumor-targeting properties of the pHLIP-functionalized nanoplatform, which ensures efficient PDT in vivo. Moreover, the nanoparticles have a long retention time in the bloodstream, indicating their stability in vivo. Overall, we provide an example of a UCNP-based nanosystem with tumor-targeting properties to perform efficient PDT both in vitro and in vivo.
上转换纳米粒子（UCNPs）由于其特殊的上转换发光特性而被广泛应用于光动力疗法（PDT），这种发光特性利用近红外（NIR）光激发光敏剂（PS）进行 PDT。如果能够增强纳米医学的癌症靶向特性，基于 UCNP 的 PDT 效率将会提高。在此，我们采用了 pH 低插入肽（pHLIP），一种癌症靶向部分，对基于 808nm 激发的 UCNP 纳米平台进行功能化，该平台具有最小的过热效应，可用于 PDT。在酸性环境下，pHLIP 可以将 cargo 特异性地递送到癌细胞中，由于酸中毒，实现了对癌细胞或肿瘤的有效主动靶向能力。pHLIP 功能化的纳米平台被组装并进行了很好的表征。该纳米平台在癌细胞中表现出高效的 NIR 照射 PDT 效应，特别是在模拟肿瘤微环境的微酸性条件下，这种有效性归因于 pHLIP 在酸性条件下对癌细胞的靶向特性，有利于纳米平台的进入。此外，pHLIP 功能化的纳米平台在具有高最大耐受剂量（MTD）的小鼠中表现出良好的安全性，这可能拓宽了体内给药的可用性。通过在乳腺癌肿瘤内注射纳米平台并随后进行 NIR 照射，实现了高效的体内抗肿瘤活性。纳米颗粒在肿瘤部位大量积累，显示出 pHLIP 功能化纳米平台优异的肿瘤靶向特性，确保了体内高效的 PDT。此外，纳米颗粒在血液中的保留时间较长，表明其在体内的稳定性。总的来说，我们提供了一个具有肿瘤靶向特性的基于 UCNP 的纳米系统的实例，该系统在体外和体内都能实现高效的 PDT。
