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Redox-activated photosensitizers for visualizing precise diagnosis and potentiating cancer therapy

COORDINATION CHEMISTRY REVIEWS 2024年 507卷

作者： fu, shuwen Chen, Zixuan Li, Li Wu, Yinwei Liao, Yalan Li, Xingshu Fuzhou Univ Coll Chem Fujian Prov Key Lab Canc Metastasis Chemoprevent & Fuzhou 350108 Peoples R China

Cancer still threats human health rigorously. Most current options of photosensitizers (PSs) are plagued with "always on", accounting for limited signal-to-noise ratio in the lesions and undesired side effects in normal tissues. Inspired by the redox imbalance of tumor microenvironment, redox-activated PSs (RA-PSs) are coming to frontiers that enhance diagnosis accuracy and treatment efficiency. Herein, the progress of PSs-based therapy is outlined. furthermore, the design strategies of RA-PSs are discussed, including potential mechanism and linkage to obtain on -demand switchable optical signals. Moreover, versatile RA-PSs for real-time visualization and therapy are highlighted. Finally, future prospects and challenges are spotlighted.

关键词： Redox imbalance Activatable photosensitizer Precise tumor imaging Cancer therapy

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Efficient hydroxyl radical generation of an activatable phthalocyanine photosensitizer: oligomer higher than monomer and nanoaggregate

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CHEMICAL SCIENCE 2024年第28期15卷 10980-10988页

作者： Li, Li Liao, Yalan fu, shuwen Chen, Zixuan Zhao, Tinghe Fang, Luyue Li, Xingshu Fuzhou Univ Coll Chem Fujian Prov Key Lab Canc Metastasis Chemoprevent & Fuzhou 350108 Peoples R China

It remains a challenge to develop a single-component organic photosensitizer that efficiently produces hydroxyl radicals ((OH)-O-center dot) without oxygen involvement, especially while maintaining tumor-targeting capability. Herein, we propose an intelligent molecular design strategy whereby a tumor-targeted phthalocyanine is initially (OH)-O-center dot-free and can be activated by overexpressed beta-nicotinamide adenine dinucleotide sodium salt hydrate (NAD(P)H) in hypoxic tumors to efficiently produce (OH)-O-center dot under light irradiation. furthermore, the oligomer models based on the phthalocyanine molecules were constructed by a supramolecular regulation strategy, which were in an intermediate state between monomer and nanoaggregate, to achieve enhanced (OH)-O-center dot generation. The level of NAD(P)H in cancer cells can be exhausted through two pathways, including spontaneous redox and the photocatalytic redox of phthalocyanines. As a result, the in vivo and in vitro assays illustrated that the oligomeric phthalocyanine containing N-O units (OligPcNOB) can specifically target cancer cells and tumor tissue with overexpressing biotin receptors. OligPcNOB exhibited significant photocytotoxicity even in an extremely low oxygen environment and successfully inhibited tumor progression. An oligomer model based on an activatable photosensitizer was constructed using an intelligent molecular design and supramolecular regulation strategy and demonstrated enhanced (OH)-O-center dot generation compared to the model of monomer and nanoaggregate.

关键词： Photosensitizers

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Pure drug nano-assemblies: A facile carrier-free nanoplatform for efficient cancer therapy

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Acta Pharmaceutica Sinica B 2022年第1期12卷 92-106页

作者： shuwen fu Guanting Li Wenli Zang Xinyu Zhou Kexin Shi Yinglei Zhai School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Department of Periodontology School and Hospital of StomatologyChina Medical UniversityLiaoning Provincial Key Laboratory of Oral DiseaseShenyang 110016China Bio-system Pharmacology Graduate School of MedicineFaculty of MedicineOsaka UniversityOsaka 565-0871Japan Department of Biomedical Engineering School of Medical DeviceShenyang Pharmaceutical UniversityShenyang 110016China

Nanoparticulate drug delivery systems(Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related ***, pure drug nano-assemblies(PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.

关键词： Nanotechnology Carrier-free Self-assembly Combination therapy Cancer treatment Pure drug Nanomedicine

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A near-infrared naphthalocyanine photosensitizer with superior light absorption and renal clearance for type-I photodynamic and photothermal combination therapy

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CHINESE CHEMICAL LETTERS 2025年第6期36卷

作者： Li, Li Wen, Jiale Zhang, Xiaojun fu, shuwen Chen, Zixuan Huang, Kai Fang, Luyue Zhao, Tinghe Zhang, Peipei Li, Xingshu Fuzhou Univ Coll Chem Fujian Prov Key Lab Canc Metastasis Chemoprevent & Fuzhou 350108 Peoples R China

Currently, it is still a challenge to develop an organic photosensitizer (PS) with outstanding near-infrared absorption, low O2 dependence, precise tumor targeting and rapid clearance through the kidney to improve the overall outcome of phototherapy. In this study, we have designed an organic PS (NcPB) with an excellent near-infrared light absorption through a refined molecular strategy. Meanwhile, NcPB was assembled into nanoparticles with different sizes (NanoNcPB-1 and NanoNcPB-0) by a supramolecular modulation strategy. As the results, the nanoparticle with an ultra-small size (NanoNcPB-1) generated a large number of superoxide anion (O2 center dot-) in a low-O2 -dependent manner and release plenty of heat. furthermore, the results of in vivo experiments demonstrated that NanoNcPB-1 actively accumulated in tumor tissues and showed a 92 % tumor inhibition after photodynamic and photothermal combination therapy. More importantly, NanoNcPB-1 could be rapidly cleared from the body of mice via the renal pathway, which alleviates potential side effects of prolonged retention of PS in the circulation. (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

关键词： Naphthalocyanine Near-infrared absorption Renal clearance Superoxide anion Type-I photosensitizer

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Fine-tuning the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies via branched aliphatic functionalization

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Nano Research 2024年第4期17卷 2908-2918页

作者： Guanting Li Fengli Xia Hongying Xiao Shunzhe Zheng shuwen fu Han Qiao Qianhui Jin Xuanbo Zhang Dun Zhou Chutong Tian Jin Sun Zhonggui He Bingjun Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmaceutics College of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China Emergency Department The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China

Small-molecule prodrug nanoassemblies have emerged as efficient antitumor drug delivery ***,in the case of camptothecins-based prodrug nanoassemblies,linear aliphatic side chain modification often results in rod-shaped or irregularly shaped nanoassemblies,which are highly unfavorable for sterilization through filtration,and may cause capillary blockage upon intravenous *** rational design of camptothecins-based prodrug nanoassemblies remains a ***,we propose that branched aliphatic alcohol(BAA)functionalization could fine-tune the structure-tolerance-antitumor efficacy axis of prodrug ***,four SN38-BAA prodrugs were synthesized by conjugating 7-ethyl-10-hydroxycamptothecin(SN38)with BAAs of varying lengths via a tumor redox-responsive disulfide bond,which self-assemble into uniform spherical *** length of BAA was found to significant impact the multiple drug delivery process,including colloidal stability,drug release profiles and ***,SN38-C21 NPs(SN38-11-heneicosanol nanoparticles),featuring the longest BAA,showcased multiple therapeutic advantages,ultimately culminating the optimal antitumor efficacy and *** findings underscore the potential of BAA functionalization in strengthening the therapeutic outcomes of prodrug nanoassemblies,and provide valuable insights for developing translational camptothecins-based nanomedicines.

关键词： prodrug nanoassembly self-assembly antitumor efficacy tolerance 7-ethyl-10-hydroxycamptothecin(SN_(3)8)

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Emerging platinum(0) nanotherapeutics for efficient cancer therapy

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JOURNAL OF CONTROLLED RELEASE 2022年 352卷 276-287页

作者： Qiao, Han Chen, Zhichao fu, shuwen Yu, Xiang Sun, Mengchi Zhai, Yinglei Sun, Jin Shenyang Pharmaceut Univ Sch Pharm Shenyang 110016 Peoples R China Shenyang Pharmaceut Univ Wuya Coll Innovat Dept Pharmaceut Shenyang 110016 Liaoning Peoples R China Shenyang Pharmaceut Univ Sch Med Devices Shenyang 110016 Liaoning Peoples R China Zhejiang Univ Affiliated Cent Hosp Huzhou Cent Hosp Affiliated Huzhou HospSch MedHuzhou Univ Huzhou Peoples R China Shenyang Pharmaceut Univ Wuya Coll Innovat Dept Pharmaceut 103 Wenhua Rd Shenyang 110016 Liaoning Peoples R China Shenyang Pharmaceut Univ Sch Med Devices Dept Biomed Engn Shenyang 110016 Liaoning Peoples R China

Platinum (Pt)-based chemotherapy has been necessary for clinical cancer treatment. However, traditional bivalent drugs are hindered by poor physicochemical properties, severe toxic side effects, and drug resistance. Currently, elemental Pt(0) nanotherapeutics (NTs) have emerged to tackle the dilemma. The inherent acid -responsiveness of Pt(0) NTs could help to improve tumor selectivity and alleviate toxic effects. Moreover, the metal nature of Pt facilitates the great combination of Pt(0) NTs with photothermal and photodynamic therapy and imaging-guided diagnosis. Based on recent important researches, this review provides an updated intro-duction to Pt(0) NTs. First, the challenges of traditional Pt-based chemotherapy have been outlined. Then, Pt(0) NTs with multiple applications of tumor theranostics have been overviewed. furthermore, the combinations of Pt (0) NTs with other therapeutical modalities are introduced. Last but not least, we envision the possible challenges and prospects associated with Pt(0) NTs.

关键词： Pt(0) nanotherapeutics Acid-responsiveness Metal nature Tumor theranostics Therapeutical modalities

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Effectiveness of recurrent laryngeal nerve monitoring on nerve paralysis during open McKeown esophagectomy: a prospective, cohort study

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LANGENBECKS ARCHIVES OF SURGERY 2025年第1期410卷 1-9页

作者： fu, shuwen Guo, Ying Lu, Xiaofan Song, Xiong Qin, Weiyi Zheng, Liquan Huang, Xiaofeng Xie, Manxiu Lu, Yali Lai, Renchun Sun Yat Sen Univ Canc Ctr Guangdong Prov Clin Res Ctr CancDept Anesthesiol State Key Lab Oncol South ChinaGuangdong Esophage Guangzhou 510060 Peoples R China Sun Yat Sen Univ Canc Ctr Guangdong Prov Clin Res Ctr Canc State Key Lab Oncol South ChinaDept Clin Res Guangzhou 510060 Peoples R China Gansu Prov Canc Hosp Dept Anesthesiol Lanzhou Peoples R China Sun Yat Sen Univ Hosp Stomatol Guanghua Sch Stomatol Dept Anesthesiol 74 Zhongshan Rd 2 Guangzhou Peoples R China

BackgroundRecurrent laryngeal nerve paralysis (RLNP) is a critical postoperative complication in esophagectomy. Intraoperative nerve monitoring (IONM) is a technique that can be used in high-risk surgeries to prevent, identify, and mitigate nerve damage. In this prospective study, we evaluated the feasibility and effectiveness of IONM in open McKeown esophagectomy for esophageal *** December 2020 to September 2023, 88 patients diagnosed with esophageal cancer were enrolled to receive IONM for open McKeown esophagectomy at Cancer Center, Sun Yat-sen University. The primary outcome was the incidence of RLNP after extubation. The secondary outcomes were postoperative complications, number of dissected lymph nodes, length of hospital stay, ICU duration and number of *** total of 83 patients were included in the final analysis. The incidence of RLNP after extubation was 30.1%. The occurrence of postoperative pulmonary complications was 20.5%. The median hospital stays were 13 days. The incidence of anastomotic leakage was 13.3%. No in-hospital deaths were reported. Postoperative RLNP prolonged the length of hospital stay (P = 0.042).ConclusionOur findings indicated that IONM could potentially be associated with a possible reduction in RLNP incidence following open McKeown esophagectomy for esophageal cancer. However, future research including well-designed randomized controlled trials may be beneficial to clarify these preliminary *** registration numberChiCTR2000029687https://***/***?proj=49103Trial registration numberChiCTR2000029687https://***/***?proj=49103

关键词： Intraoperative nerve monitoring Recurrent laryngeal nerve paralysis Open McKeown esophagectomy Esophageal cancer

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Combined Ultrasound-Guided Thoracic Paravertebral Nerve Block with Subcostal Transversus Abdominis Plane Block for Analgesia After Total Minimally Invasive Mckeown Esophagectomy: A Randomized, Controlled, and Prospective Study

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PAIN AND THERAPY 2023年第2期12卷 475-489页

作者： Xu, Mei Feng, Yuerou Song, Xiong fu, shuwen Lu, XiaoFan Lai, Jielan Lu, Yali Wang, Xudong Lai, Renchun Sun Yat Sen Univ Canc Ctr Dept Anesthesiol State Key Lab Oncol Southern China Collaborat Innovat Canc Med 651 Dongfeng Dong Lu Guangzhou Guangdong Peoples R China Guangdong Esophageal Canc Inst Guangzhou Peoples R China

IntroductionThoracic paravertebral block (TPVB) and subcostal transverse abdominis plane block (TAP) have been considered to provide an effective analgesic effect for laparoscopic and thoracoscopic surgery, respectively. The purpose of this randomized, controlled, and prospective study was to evaluate the analgesic effect of TPVB combined with TAP in patients undergoing total minimally invasive Mckeown *** February 2020 and December 2021, a total of 168 esophageal cancer patients undergoing McKeown esophagectomy at the Cancer Center of Sun Yat-Sen University, China, were randomly assigned to receive patient-controlled epidural analgesia alone (group PCEA, n = 56), patient-controlled intravenous analgesia alone (group PCIA, n = 56), and TPVB combined with TAP and patient-controlled intravenous analgesia (group PVB, n = 56). The primary outcome was a visual analogue scale (VAS) pain score on movement 48 h postoperatively. Secondary endpoints were pain scores at other points, intervention-related side effects, surgical complications, and length of intensive care unit and hospital stay. For the VAS pain score, the Kruskal-Wallis method was conducted for comparison of 3 treatment groups and further pairwise comparison with Bonferroni *** movement, the VAS in the PVB group was higher than that in the PCEA group at 48 h, 72 h, 96 h, and 120 h postoperatively (p < 0.05) except in the postoperative anesthesia care unit (PACU) and 24 h postoperatively. The VAS in the PCIA group was higher than the PCEA and PVB groups in the first 4 days after surgery. The pulmonary complication rate in the PCIA group was significantly higher than the rate in the PCEA [95% Confidence Interval 0.214 (0.354, 0.067), p = 0.024].ConclusionsCombined TPVB and TAP was more effective than intravenous opioid analgesia alone, while PCEA was more effective than TPVB combined with TAP and intravenous opioid analgesia for patients after McKeown esophagectomy.

关键词： Thoracic paravertebral block Transverse abdominis plane block McKeown esophagectomy Postoperative pain

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Evaluation of Efficacy of Neoadjuvant Immunochemotherapy for Cervical Metastatic Squamous Cell Carcinoma of Unknown Primary

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CANCER MEDICINE 2025年第9期14卷 e70869页

作者： Gao, Xianlu fu, shuwen Yang, Chulin Jiang, Wenmei Liang, Jiadong Li, Ruiyu Yan, Shida Du, Mingyuan Yang, Shiyan Zhang, Quan Chen, Shuwei Sun Yat Sen Univ Dept Head & Neck Surg Canc Ctr Guangzhou Peoples R China State Key Lab Oncol South China Guangzhou Peoples R China Guangdong Prov Clin Res Ctr Canc Guangzhou Peoples R China Sun Yat Sen Univ Hosp Stomatol Dept Anesthesiol Guangzhou Peoples R China Sun Yat Sen Univ Guanghua Sch Stomatol Guangzhou Peoples R China Chinese Acad Sci Zhejiang Canc Hosp Hangzhou Inst Med Dept Thyroid Surg Hangzhou Peoples R China

Purpose: This study aims to evaluate the antitumor activity of neoadjuvant immunochemotherapy in patients with cervical metastatic squamous cell carcinoma of unknown primary (CMSCCUP), providing a new idea for its treatment. Method: We retrospectively examined the medical records from Sun Yat-sen University Cancer Center to identify patients with CMSCCUP from July 2020 to November 2023. CMSCCUP's diagnoses are based on the results of biopsy and imaging examination. All patients received PD-1 inhibitors combined with chemotherapy: paclitaxel (Albumin-bound) 260 mg/m2 and cisplatin 60 mg/m2 every 3 weeks for two or more cycles as their initial treatment. Clinical response after neoadjuvant immunochemotherapy was assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Surgery, radiotherapy, or chemoradiotherapy was performed subsequently based on the imaging evaluation results. Outcomes included overall survival (OS) and disease-free survival (DFS). Result: After neoadjuvant immunochemotherapy, the objective response rate (ORR) was 84.2%;complete response (CR), partial response (PR), and stable disease (SD) were 36.8%, 47.4%, and 15.8%, respectively. Of the 9 patients (42.9%) who underwent surgery after neoadjuvant immunochemotherapy, 7 (77.8%) achieved pathological complete response (pCR). No severe treatment-related adverse events occurred. The most common treatment-related adverse events were Grade 1-2 fatigue (11/14, 78.6%), decreased appetite (11/15, 73.3%), and increased aspartate transaminase (12/20, 60.0%). One (1/20, 5.0%) patient experienced Grade 3 anemia. The 2-year overall survival (OS) and 2-year disease-free survival (DFS) rates were 94.4% and 89.4%, respectively. Conclusion: Neoadjuvant immunochemotherapy showed favorable efficacies, anticipated outcomes, and tolerable toxicity for patients with CMSCCUP. More clinical practice and clinical studies are still needed to confirm further.

关键词： cervical metastatic squamous cell carcinoma of unknown primary immunotherapy neoadjuvant therapy PD-1 inhibitors squamous cell carcinoma of the head and neck

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基于替代模型的缆索承重桥梁固有频率预测

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铁道科学与工程学报 2023年第7期20卷 2594-2603页

作者：马亚飞付曙雯何羽鲁乃唯王磊长沙理工大学土木工程学院湖南长沙410114

大跨缆索承重桥梁空间组成复杂,影响参数多,结构动力分析具有显著不确定性。提出一种基于支持向量机的结构固有频率预测方法,采用遗传算法和交叉验证算法进行超参数寻优,实现了复杂高维结构参数与动力响应间的非线性映射建模。以南溪长... 详细信息

大跨缆索承重桥梁空间组成复杂,影响参数多,结构动力分析具有显著不确定性。提出一种基于支持向量机的结构固有频率预测方法,采用遗传算法和交叉验证算法进行超参数寻优,实现了复杂高维结构参数与动力响应间的非线性映射建模。以南溪长江大桥为背景,采用ANSYS三维建模对悬索桥进行模态分析,选用拉丁超立方试验抽取样本数据保证结果的全面性,考虑参数敏感性和样本量对模型预测精度和效率的影响,利用MATLAB函数实现固有频率的回归预测。研究结果表明:遗传支持向量机替代模型样本量达350组时,均方误差值为7.8482×10^(−4)基本收敛;样本量在50~1000组范围内,经遗传算法参数寻优的预测误差随样本量增加的变化趋势与交叉验证算法较一致,但遗传算法精度更高;在350组样本量下,遗传算法单次寻优耗时仅为交叉验证算法的37.06%。准确预测基频后,进一步预测了南溪长江大桥第3阶、第5阶和第7阶固有频率,预测结果的均方误差和平均绝对误差均小于0.005,满足精度要求。研究成果可为复杂结构动力分析和安全状态评估提供一种精确高效的分析方法。

关键词：桥梁固有频率有限元分析支持向量机遗传算法替代模型

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