Activatable NIR-II Lanthanides-Polymetallic Oxomolybdate Hybrid Nanosensors for Monitoring Chemotherapy Induced Enteritis

Chemotherapy-induced enteritis is one of the side effects associated with cancer therapy, which significantly affects the treatment effect, but there is no effective clinical detection method that can early diagnose its occurrence and progression. Here, a series of second near-infrared window (NIR-II) hybrid nanosensors are designed that consisted of lanthanide nanoparticles and β-Mo2C-derived polymetallic oxomolybdate nanoclusters (Ln@POM). Based on the high sensitivity of POM to reactive oxygen species (ROS) closely related to chemotherapy-induced enteritis, the NIR-II luminescence intensity and lifetime of Ln@POM (Ln: Yb³⁺, Nd³⁺, Ho³⁺, Tm³⁺, Er³⁺) show excellent responsiveness to H₂O₂ and HClO with the detection limit down to 0.15 and 0.14 µm , respectively. Utilizing Nd@POM as a ROS-activated NIR-II nanosensor, the chemotherapeutic enteritis is successfully detected within 7 h after induction of chemotherapy drugs, which is significantly earlier than the gold standard method (immunohistochemistry, 24 h). These results demonstrate that the designed hybrid nanosensors are promising optical tools for the early diagnosis of ROS-related diseases.     

Fluorescent Imaging‐Guided Chemotherapy‐and‐Photodynamic Dual Therapy with Nanoscale Porphyrin Metal–Organic Framework

Imaging‐guided therapy systems (IGTSs) are revolutionary techniques used in cancer treatment due to their safety and efficiency. IGTSs should have tunable compositions for bioimaging, a suitable size and shape for biotransfer, sufficient channels and/or pores for drug loading, and intrinsic biocompatibility. Here, a biocompatible nanoscale zirconium‐porphyrin metal–organic framework (NPMOF)‐based IGTS that is prepared using a microemulsion strategy and carefully tuned reaction conditions is reported. A high content of porphyrin (59.8%) allows the achievement of efficient fluorescent imaging and photodynamic therapy (PDT). The 1D channel of the Kagome topology of NPMOFs provides a 109% doxorubicin loading and pH‐response smart release for chemotherapy. The fluorescence guiding of the chemotherapy‐and‐PDT dual system is confirmed by the concentration of NPMOFs at cancer sites after irradiation with a laser and doxorubicin release, while low toxicity is observed in normal tissues. NPMOFs are established as a promising platform for the early diagnosis of cancer and initial therapy.     

PD‐1 Blockade for Improving the Antitumor Efficiency of Polymer–Doxorubicin Nanoprodrug

Chemotherapy is well recognized to induce immune responses during some chemotherapeutic drugs‐mediated tumor eradication. Here, a strategy involving blocking programmed cell death protein 1 (PD‐1) to enhance the chemotherapeutic effect of a doxorubicin nanoprodrug HA‐Psi‐DOX is proposed and the synergetic mechanism between them is further studied. The nanoprodrugs are fabricated by conjugating doxorubicin (DOX) to an anionic polymer hyaluronic acid (HA) via a tumor overexpressed matrix metalloproteinase sensitive peptide (CPLGLAGG) for tumor targeting and enzyme‐activated drug release. Once accumulated at the tumor site, the nanoprodrug can be activated to release antitumor drug by tumor overexpressed MMP‐2. It is found that HA‐Psi‐DOX nanoparticles can kill tumor cells effectively and initiate an antitumor immune response, leading to the upregulation of interferon‐γ. This cytokine promotes the expression of programmed cell death protein‐ligand 1 (PD‐L1) on tumor cells, which will cause immunosuppression after interacting with PD‐1 on the surface of lymphocytes. The results suggest that the therapeutic efficiency of HA‐Psi‐DOX nanoparticles is significantly improved when combined with checkpoint inhibitors anti‐PD‐1 antibody (α‐PD1) due to the neutralization of immunosuppression by blocking the interaction between PD‐L1 and PD‐1. This therapeutic system by combining chemotherapy and immunotherapy further increases the link between conventional tumor therapies and immunotherapy.     

BRCA1基因多态性与转移性食管鳞癌顺铂联合卡培他滨化疗敏感性及预后关系

目的：研究乳腺癌易感基因1(breast cancer susceptibility gene1,BRCA1)单核苷酸多态性(single nucleotide polymorphism,SNP)对转移性食管鳞癌患者化疗敏感性及生存预后的影响。方法：选取2016年6月至2020年2月于苏州科技城医院收治的153例初治转移性食管鳞癌患者,均给予顺铂联合卡培他滨化疗。首次化疗前抽静脉血5ml提取DNA,应用TaqMan探针法检测BRCA1基因rs8176318G/T 、rs799917T/C和rs1799966T/C多态性位点的基因型,探讨不同基因型之间化疗客观反应率 (objective response rate,RR)和总生存期(overall survival,OS)的差异。结果：rs799917T/C多态性与转移性食管鳞癌化疗敏感性密切相关,TT、TC、CC基因型化疗有效率呈逐渐升高趋势(TT 22.5%、TC 38.6%、CC 55.3%,χ2=8.041,P=0.018)。CC基因型化疗反应率为TT基因型的4.154倍 (95%CI：1.549~11.141,χ2=8.007,P=0.005);TC+CC基因型化疗反应率为TT基因型的2.678倍 (95%CI：1.160~6.179,χ2=5.329,P=0.021)。Kaplan-Meier分析显示rs1799966T/C多态性与患者生存时间相关, TT、TC和CC基因型携带者中位OS呈逐渐延长趋势 (TT8.5月、TC12.1月、CC13.8月,χ2=11.864,P=0.003); TC+CC基因型患者中位OS为12.6个月,与TT组相比明显延长(χ2=10.515,P=0.001)。COX回归模型分析结果显示,rs1799966T/C多态性仍是影响患者OS的独立预后因素。未发现rs8176318G/T多态性与化疗反应及预后之间存在统计学关联。结论：BRCA1基因rs799917多态性与转移性食管鳞癌顺铂联合卡培他滨化疗敏感性相关,rs1799966多态性可能影响患者的生存预后。     

GnRHa用于化疗后生育力保护的循证医学研究进展

随着肿瘤患者长期生存率提高,年轻肿瘤患者化疗后生育力保护的要求日益凸显。早期研究显示促性腺激素释放激素激动剂（GnRHa）具有一定的生育力保护作用,但近年来相关研究显示其保护作用存在争议。本文综述GnRHa用于常见肿瘤患者生育力保护的临床研究,挖掘其循证医学证据,以期为临床合理用药提供参考。     

pH‐ and NIR Light‐Responsive Micelles with Hyperthermia‐Triggered Tumor Penetration and Cytoplasm Drug Release to Reverse Doxorubicin Resistance in Breast Cancer

The acquisition of multidrug resistance (MDR) is a major hurdle for the successful chemotherapy of tumors. Herein, a novel hybrid micelle with pH and near‐infrared (NIR) light dual‐responsive property is reported for reversing doxorubicin (DOX) resistance in breast cancer. The hybrid micelles are designed to integrate the pH‐ and NIR light‐responsive property of an amphiphilic diblock polymer and the high DOX loading capacity of a polymeric prodrug into one single nanocomposite. At physiological condition (i.e., pH 7.4), the micelles form compact nanostructure with particle size around 30 nm to facilitate blood circulation and passive tumor targeting. Meanwhile, the micelles are quickly dissociated in weakly acidic environment (i.e., pH ≤ 6.2) to release DOX prodrug. When exposed to NIR laser irradiation, the hybrid micelles can trigger notable tumor penetration and cytosol release of DOX payload by inducing tunable hyperthermia effect. In combination with localized NIR laser irradiation, the hybrid micelles significantly inhibit the growth of DOX‐resistant MCF‐7/ADR breast cancer in an orthotopic tumor bearing mouse model. Taken together, this pH and NIR light‐responsive micelles with hyperthermia‐triggered tumor penetration and cytoplasm drug release can be an effective nanoplatform to combat cancer MDR.     

腹腔镜下CA724表达与新辅助化疗在进展期胃癌中的应用

目的:探索CA724表达与新辅助化疗结合腹腔镜D2根治术治疗进展期胃癌疗效及预后的相关性。方法:回顾性分析我院2017年1月-2018年1月期间收治的局部进展期胃癌患者68例临床资料,根据治疗方案的不同分为对照组30例、研究组38例,对照组采取单纯腹腔镜D2根治术治疗,研究组在腹腔镜D2根治术的基础上结合新辅助化疗治疗,对比两组总有效率、预后情况、CA724表达水平以及阳性率差异,采用Spearman相关性分析法检验CA724水平与患者疗效及预后的关系。结果:研究组患者的总有效率(60.53%)高于对照组患者(43.33%),但差异无统计学意义(χ²=1.989,P=0.158);研究组患者的3年生存率(78.95%)明显高于对照组患者(56.67%),复发转移率(18.42%)则明显低于对照组患者(46.67%),差异有统计学意义(χ²=3.899、6.266,P=0.048、0.012);两组患者术后的CA724表达水平和阳性率均较本组治疗前明显下降,且研究组的下降幅度大于对照组(χ²/t=5.643、6.546,P<0.001);CA724的表达平与患者的疗效及三年生存率呈负相关(r=-0.625、-0.732和-0.832、-0.839,P均<0.001),与患者的复发、转移率呈正相关(r=0.662和0.873,P均<0.001)。结论:血清CA724的表达水平及阳性率变化可在一定程度上反映行新辅助化疗结合腹腔镜D2根治术治疗进展期胃癌患者的疗效及预后情况,当CA724的表达水平及阳性率较低时,提示患者的疗效及预后情况较好,具有一定的临床意义。     

膀胱癌化疗药物增敏机制研究进展

近年来化疗耐药严重制约着膀胱癌的治疗效果,术后复发率和转移率居高不下。因此,逆转膀胱癌化疗耐药性,寻找有效的化疗增敏靶点并探究其机制十分重要。目前临床上多采用经尿道膀胱肿瘤切除术,术后选择辅助化疗药物进行治疗,常用化疗药物包括顺铂、吉西他滨、阿霉素、表柔比星等。目前实现这些药物化疗增敏的靶点基因和分子在膀胱癌细胞中呈现不同的表达状态,且通过这些靶点实现增敏的机制也各有不同。本文将就膀胱癌化疗药物增敏靶点及机制的研究进展进行综述,以期为膀胱癌的化疗增敏探索新的思路。