Radiotherapy has been extensively used to treat cancer patients because it can effectively damage most solid tumors without penetration limits. A hypoxic microenvironment in solid tumors leads to severe radioresistance and expression of hypoxic inducible factor-1 (HIF-1), which results in poor efficacy of radiotherapy alone. Herein, we report the excellent efficacy of radiotherapy achieved using a new type of yolk−shell Cu 2−x Se@PtSe (CSP) nanosensitizer functionalized with the HIF-1α inhibitor acriflavine (ACF). We prepare the CSP nanosensitizer through the interfacial redox reactions between chloroplatinic acid and Cu 2−x Se nanoparticles (CS) and then functionalize the nanosensitizer with ACF through their electrostatic interactions. We show that the synthesized CSP nanosensitizer can arrest the cell cycle (i.e., at the gap 2/mitosis (G 2 /M) phases) of tumor cells to enhance their sensitivity to X-rays and decompose endogenous H 2 O 2 into O 2 to reduce hypoxia and increase the production of reactive oxygen species, which leads to severe damage to DNA double strands and apoptosis of tumor cells. We also show that the ACF on the surface of CSP nanoparticles can effectively reduce the expression of HIF-1α. All these effects lead to a low vascular endothelial growth factor, low density of microvessels in tumor, decreased cell proliferation, and increased cell apoptosis, which synergistically and drastically enhance the efficacy of radiotherapy. This work provides insights and guidance for developing novel nanosensitizers to enhance the efficacy of radiotherapy.

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The metastasis of breast cancer mainly occurs through the axillary lymph node and blood circulation systems. It is extremely difficult to know when the cancer cells start to metastasize; however, early detection of breast cancer metastasis is crucial and challenging to enable surgical removal of the primary tumor and perform a systematic lymphadenectomy to eliminate invasion of the tumor. Herein, we report real-time tracking of the metastasis of orthotopic breast cancer with background-free near-infrared long-persistent luminescence (NIR-PL) imaging, and its guidance for the surgical removal of lymph nodes. The NIR-PL imaging is based on Cr3+/Nd3+ codoped ZnGa2O4 (A-ZGCN) nanoparticles with a superlong afterglow time of more than 15 days. We show that the detection sensitivity of metastasis of cancer cells with the NIR-PL imaging is higher than the classic bioluminescence imaging. We find that the metastasis of breast cancer cells to lymph nodes occurred as early as on the third day after orthotopic inoculation of breast cancer cells and followed an order of the proper axillary lymph node (PALN, day 3) > accessory axillary lymph node (AALN, day 6) > accessory mandibular lymph node (AMLN, day 9) > mandibular lymph node (MLN, day 25). In addition, we show that the NIR-PL nanoprobes (i.e., A-ZGCN NPs) displayed 17% radioenhancement, which was used for radiotherapy of orthotopic breast cancer to further prevent and reduce its metastasis to other organs. The radiotherapy treatment is superior to surgery for removal of the tumor accompanied by a NIR-PL imaging-guided lymphadenectomy. Our work demonstrates the great potential of NIR-PL imaging and the corresponding nanoprobes for tracking metastasis of cancer cells and for radiotherapy.

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BACKGROUND Single incision plus one port left-side approach (SILS+1/L) totally laparoscopic distal gastrectomy (TLDG) is an emerging technique for the treatment of gastric cancer. Reduced port laparoscopic gastrectomy has a number of potential advantages for patients compared with conventional laparoscopic gastrectomy: relieving postoperative pain, shortening hospital stay and offering a better cosmetic outcome. Nevertheless, there are no previous reports on the use of SILS+1/L TLDG with uncut Roux-en-Y (uncut R-Y) reconstruction. AIM To investigate the initial feasibility of SILS+1/L TLDG with uncut Roux-en-Y digestive tract reconstruction (uncut R-Y reconstruction) to treat distal gastric cancer. METHODS A total of 21 patients who underwent SILS+1/L TLDG with uncut R-Y reconstruction for gastric cancer were enrolled. All patients were treated at The Second Hospital of Shandong University. Reconstructions were performed intracorporeally with 60 mm endoscopic linear stapler and 45 mm no-knife stapler. The clinicopathological characteristics, surgical details, postoperative short-term outcomes, postoperative follow-up upper gastrointestinal radiography findings and endoscopy results were analyzed retrospectively. RESULTS All SILS+1/L operations were performed by SILS+1/L TLDG successfully. The patient population included 13 men and 8 women with a mean age of 48.2 years (ranged from 40 years to 70 years) and median body mass index of 22.8 kg/m 2 . There were no conversions to open laparotomy, and no other port was placed. The mean operation time was 146 min (ranged 130-180 min), and the estimated mean blood loss was 54 mL (ranged 20-110 mL). The mean duration to flatus and discharge was 2.3 (ranged 1-3.5) and 7.3 (ranged 6-9) d, respectively. The mean number of retrieved lymph nodes was 42 (ranged 30-47). Two patients experienced mild postoperative complications, including surgical site infection (wound at the navel incision) and mild postoperative pancreatic fistula (grade A). Follow-up upper gastrointestinal radiography and endoscopy were carried out at 3 mo postoperatively. No patients experienced moderate or severe food stasis, alkaline gastritis or bile reflux during the follow-up period. No recanalization of the biliopancreatic limb was found. CONCLUSION SILS+1/L TLDG with uncut R-Y reconstruction could be safely performed as a reduced port surgery.