DNA-assembled visible nanodandelions with explosive hydrogen-bond breakage achieving uniform intra-tumor distribution (UITD)-guided photothermal therapy.

Photothermal therapy (PTT) has received increasing attention for treating tumors. However, a long-standing challenge in PTT is non-uniform distribution of photothermal agents (PAs) in tumor tissues, resulting in limited therapeutic efficiency. Herein, inspired by dandelions blowing away by the wind, we have designed a DNA-assembled visible GRS-DNA-CuS nanodandelion, which can achieve uniform intra-tumor distribution (UITD) of PAs, thus enhancing the photothermal therapeutic efficiency. GRS-DNA-CuS is featured by the formation of hydrogen bond between the core of single-strand DNA-modified Raman nanoprobes (GRS) and the shell of complementary single-strand DNA-modified CuS PAs. Under Raman imaging-guided 1st NIR irradiation, hydrogen bond in GRS-DNA-CuS is explosively broken, resulting in large-sized GRS-DNA-CuS (∼135 nm) be completely dissociated into GRS and ultra-small CuS PAs (∼12 nm) within 1 min. Such an explosive dissociation instantly enhances the local concentration of ultra-small CuS PAs and slightly rises intra-tumor temperature, thus increasing the diffusion coefficient of PAs and promoting their UITD. This UITD of CuS PAs enhances the photothermal anti-tumor effects. Three out of five tumors are completely eliminated under photoacoustic imaging-guided 2nd NIR irradiation. Overall, this study provides one UITD-guided PTT strategy for highly effective tumor treatment by exerting explosive breakage property of hydrogen bond, broadening the application scope of DNA-assembly technique in oncology field.

A meta-analysis of biologic therapies on risk of new or recurrent cancer in patients with rheumatoid arthritis and a prior malignancy.

OBJECTIVES: To explore the risk of new and recurrent cancer in adult RA patients with prior malignancy and subsequently exposed to biologic therapies. METHODS: Separate searches were performed of PubMed, EMBASE and Cochrane Library and conference proceedings for observational studies reporting cancer incidence or recurrence in patients with RA and prior malignancy treated with biologics and conventional synthetic DMARDs (csDMARDs). Mantel-Haenszel fixed-effects method was conducted to calculate relative risk and 95% CI. RESULTS: A total of 12 studies involving 13 598 patients and 32 473 patient-years of follow-up were included (10, 3 and 1 studies for TNF inhibitors [TNFi], rituximab and anakinra, respectively). The crude incidence of new and recurrent cancer per 1000 patient-years were 34.4 for TNFi, 32.3 for rituximab, 32.3 for anakinra and 31.8 for csDMARDs. In the quantitative meta-analysis, biologics were not associated with an increased risk of new or recurrent cancer compared with csDMARDs in patients with RA and prior cancer (TNFi: relative risk = 0.95, 95% CI = 0.83, 1.09; rituximab: relative risk = 0.89, 95% CI = 0.52, 1.53). Secondary analyses of stratification of cancer types, the interval between initiation of TNFi and prior cancer diagnosis, and duration of TNFi exposure, found similar results. CONCLUSION: Compared with csDMARDs, there is no increased risk of developing cancer overall or some specific subtypes in RA patients with a prior cancer receiving biologics. More investigations are warranted to explore the risk of cancer development in individual cancer as well as to determine optimal time to initiate biologic therapy after the diagnosis of cancer or completion of cancer treatment.