Developing smart molecular probes for assisting surgeons to precisely detect cancerous tissues and to completely remove all of them during the surgery is urgently required. Conventional fluorescent probes allow for tumor detection but with limited signal-to-noise ratio. Herein, an aminopeptidase N/CD13 (APN)-activated chemiluminescent probe (APN-ACLP) is reported for sensitive imaging and precise resection of malignant tumors. The APN-ACLP probe is based on acryl-substituted phenoxy-dioxetane that is coupled with an APN-cleavable substrate via a self-immolative linker. Upon activation by APN through specific hydrolysis reaction, APN-ACLP generates spontaneously chemiluminescence signal, which offers a possibility to sensitively search tumors by simply spraying APN-ACLP on the suspicious sites. Animal imaging studies reveal that a sufficient signal contrast between the cancerous tissues and the normal counterparts can be achieved within 5 min, which can allow for rapid detection and surgical resection of tumors, particularly tiny metastatic lesions in mice model, under the guidance of chemiluminescence imaging, well manifesting its potential for image-guided surgery of malignant tumors.
Xiao-lin Hou,Xiang Dai,Jie Yang,Bin Zhang,Dong-hui Zhao,Chao-qing Li,Zhong-yuan Yin,Yuan-di Zhao,Bo Liu
The immunosuppressive tumor microenvironment has caused great obstacles to tumor immunotherapy, especially where less tumor-associated antigens are released from tumor sites. Herein, a Ag2S QD/DOX/Bestatin@PC10ARGD genetically engineered polypeptide hydrogel PC10ARGD as a sustained-release material was developed for mammary carcinoma treatment. A near-infrared silver sulfide (Ag2S) QD as a photosensitizer was encapsulated into the hydrophobic cavity formed by the self-assembly of the polypeptide nanogel (PC10ARGD) for photothermal therapy. The water-soluble drug DOX and Bestatin were integrated into the PC10ARGD hydrogel. The photothermal effect could trigger the sustained release of the DOX, which could be applied to initiate in situ vaccination. Bestatin as an immune-adjuvant drug could amplify the body's immune function. The results of in vivo therapy tests exhibited that the Ag2S QD/DOX/Bestatin@PC10ARGD hydrogel with laser irradiation could activate anti-tumor immune effects that inhibit the growth of primary tumors and distal lung metastatic nodules. Meanwhile, a safer lower-temperature with multiple laser irradiation treatment strategy exhibited more effective tumor-killing performance (84.4% tumor inhibition rate) and promoted the penetration of immune cells into the tumor tissue. The CD8+ and CD4+ cytotoxic T cells ratio was increased by 5.3 and 10 times, respectively, thus exhibiting a good prognostic signal. The multifunctional polypeptide hydrogel as a green manufacturing and engineering material is promising to serve as a cancer vaccine for anticancer applications.
危险品化学品经营许可证（带存储）