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Chemo-photothermal immunotherapy for eradication of orthotopic tumors and inhibition of metastasis by intratumoral injection of polydopamine versatile hydrogels

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1447-1459页

作者： Bo Zhuang Ting Chen Yueqi Huang Zhimei Xiao Yiguang Jin Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Department of Chemical Defense Institute of NBC DefenseBeijing 102205China

Cancer remains one of the leading causes of death globally and metastasis always leads to treatment ***,we develop a versatile hydrogel loading photothermal agents,chemotherapeutics,and immune-adjuvants to eradicate orthotopic tumors and inhibit metastasis by combinational *** networks were synthesized via the thiol-Michael addition of polydopamine(PDA)with thiolated hyaluronic *** acted as a cross-linking agent and endowed the hydrogel with excellent photothermal ***,a chemotherapeutic agent,doxorubicin(DOX),was loaded in the hydrogel viaπ-πstacking with PDA and an immune-adjuvant,CpG-ODN,was loaded via electrostatic *** release of DOX from the hydrogel was initially slow but accelerated due to near infrared light *** hydrogels showed remarkably synergistic effect against 4T1 cancer cells and stimulated plenty of cytokines secreting from RAW264.7 ***,the hydrogels eradicated orthotopic murine breast cancer xenografts and strongly inhibited metastasis after intratumoral injection and light *** high anticancer efficiency of this chemo-photothermal immunotherapy resulted from the strong synergistic effect of the versatile hydrogels,including the evoked host immune *** combinational strategy of chemo-photothermal immunotherapy is promising for highly effective treatment of breast cancer.

关键词： Breast cancer Polydopamine Hydrogel intratumoral injection Photothermal Chemotherapy Immunotherapy Metastasis

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Improving Anti-tumor Outcomes for Palliative intratumoral injection Therapy through Lecithin-Chitosan Nanoparticles Loaded with Paclitaxel-Cholesterol Complex

Improving Anti-tumor Outcomes for Palliative Intratumoral In...

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2018年第十二届中国药物制剂大会

作者：初晓阳 Wei Huang Yu-li Wang Ling-wei Meng Li-qing Chen Ming-ji Jin Lu Chen Chun-hong Gao Cheng Ge Zhong-gao Gao Chun-sheng Gao State key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology State Key laboratory of Bioactive substance and Function of Natural Medicines Department of Pharmaceutics Institute of Materia Medica Chinese academy of Medical sciences and Peking Union Medical college The 307th Hospital of the PLA

intratumoral injection is the palliative treatment to get further improvements in survival and quality of life for advanced or recurrent carcinomas patients, or the patients with severe comorbidities or a poor performance status. In this study, a solvent-injection method was used to prepare paclitaxel–cholesterol complex loaded lecithin-chitosan nanoparticles(PTX-CH-loaded LCSPs) for intratumoral injection therapy, and the physicochemical properties of NPs were well characterized. Release behavior of PTX from PTX-CH-loaded LCSPs showed a pH-sensitive pattern. The result of cell uptake assay indicated that PTXCH-loaded LCSPs could effectively penetrate cells through the energy-dependent caveolae-mediated endocytosis and macropinocytosis via Golgi apparatus. Meanwhile, PTX-CH-loaded LCSPs had superior ability to induce cell apoptosis comparing with paclitaxel solution. The in vivo anti-tumor results suggested that PTX-CH-loaded LCSPs effectively inhibited mouse mammary cancer growth and metastasis to distant organs and significantly improved survival ratio of tumor-bearing mice by intratumoral administration. In general, our study demonstrated that PTX-CH-loaded LCSPs used for palliative treatment by intratumoral injection exhibited enhanced safety and antitumor efficacy, and provided an alternative choice in the field of palliative chemotherapy.

关键词： lecithin chitosan paclitaxel nanoparticles pH responsive palliative chemotherapy intratumoral injection

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Inhibition of lung cancer stem cells self-renewal and tumorigenicity by lentivirus-delivered Bmi1 shRNA

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The Chinese-German Journal of Clinical Oncology 2011年第11期10卷 636-642页

作者： Jing Zhou Yu XU Ping Hao Yide Hu The Third Department of Oncology Institute Xinqiao Hospital Third Military Medical University Chongqing 400037 China Department of Respiratory Chengdu General Hospital of Chengdu Command Chengdu 610083 China

Objective： The aim of the study was to observe the effect of Bmil reduction on the self-renewal and tumorigenicity ability of lung cancer stem cells （LCSCs） in human lung adenocarcinoma. Methods： Human lung adenocarcinoma cells A549 were consecutively passaged in NOD/SCID mice treated with Paclitaxel weekly. The proportions of LCSCs in A549 cells and the cells from the third passage （A549-3rd） were compared. The expression of Bmil in LCSCs was silenced by intratumoral injection with lentivirus-delivered Broil small hairpin RNA （shRNA）. RT-PCR and Western blot were used to test the mRNA and protein expressions of Broil in LCSCs. The protein level of p16INK4A was analyzed by Western blotting. The self- renewal and tumorigenicity ability of LCSCs were evaluated by counting the sphere formation rate in serum-free medium and the tumor formation rate in NOD/SCID mice. Results： In vivo passaging ofA549 cells under chemotherapy pressure enriched for LCSCs. The expression of Broil in LCSCs increased. Down-regulation of Bmil by RNA interference resulted in reduced self-renewal and tumorigenicity ability of LCSCs and paralleled the increased expression of p16INK4A, a Bmil target. Conclu- sion： Broil regulates self-renewal and tumorigenicity of LCSCs by silencing some target genes, including p16INK4A.

关键词： Bmil RNA interference intratumoral injection cancer stem cells non-small cell lung cancer (NSCLC)

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Biodistribution and Anti-tumor Activities of the ^(131)I-labeled Rituximab in Nude Mice Bearing Human Burkitt's lymphoma

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Clinical oncology and cancer researeh 2009年第4期6卷 256-262页

作者： Qiang Zuo Aimin Li Xiao Yan RongchengLuo Cancer Center Nanfang Hospital the South-ern Medical University Guangzhou 510515Guangdong Province China.

OBJECTIVE To explore the biodistribution and anti-tumoractivity of ^(131)I labeled rituximab injected intratumorally orintraperitoneally in vivo in nude mice bearing Raji human Burkitt's lymphoma *** The rituximab and the mouse IgG were labeled withNa^(131)I using the IODO-GEN ***/C nude mice werexenografted with ^(131)I-Rituximab or ^(131)I-IgG and killed on the 1st,3rd,7th,and 15th day after *** tumor/non-tumor ratio(T/NT)and the dose injected in each gram of the tissue(%ID/g)from12 organs or tissues of interest,***,blood,were *** long and short axes of each tumor were measured by calipersat 2-3-day intervals after treatment,and the growth inhibition ofthe tumor was calculated using the MIRD *** When comparing intraperitoneal injection(IP)andintratumoral injection(IT)of ^(131)I-IgG,intratumoral injection of^(131)I-rituximab produced a significantly higher tumor/non-tumorratio in all tissues and organs of interest on the 1st,3rd,and 7thday,respectively(Pintratumoral injection of the ^(131)I-rituximab,whereas it wasless inhibited by other forms of the treatment(Pintratumorally inhibited tumor growth ina dose-dependent *** inhibition rate was less with alow dose(75μCi)and greater with a high dose(150μCi),yet thedifference was not significant(P>0.05).CONCLUSION Tumors can absorb the highest amount of theradiolabelled antibodies,and the tumor/non-tumor ratios in thegroup with intratumoral injection of the ^(131)I-rituximab resulted inthe optimal anti-tumor activity.

关键词： Iodine-131 anti-CD20 monoclonal antibody non-Hodgkin's lymphoma (NHL) intratumoral injection radioimmunotherapy.

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Experimental Research of Tankyrase1 Antisense Oligodeoxynucleotides on the Proliferation of Lung Cancer Cell Nodules

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Clinical oncology and cancer researeh 2010年第3期7卷 181-186页

作者： Chong LI Tan LI Zhong-li ZHAN Department of Pathology Tianjin TCM University the First Affiliated Hospital Tianjin 300191 China. Department of Pathology Tianjin Medical University Cancer Institute & Hospital Tianjin 300060. China.

OBJECTIVE To observe the effects of sense and antisense oligodeoxynucleotides of tankyrase 1 （TANK1-SODN and TANK1-ASODN） on murine tumor growth following intratumoral injection, investigate the actual suppressing result and mechanism of TANK1-ASODN on cancer cell proliferation, and discuss the possibility of using it in gene therapy on human lung cancer cells. METHODS After BALB/c nude mice had been subcutaneously inoculated with human lung cancer cell line CALU and it had grown into tumor nodules, we distributed these mice randomly into 3 groups： 4 in saline treatment group, and 5 each in TANK1-SODN group, and TANK1-ASODN groups. Then multiple direct intratumoral injections of synthesized TANK1-ASODN given continuously into tumor nodules for 16 days, this was compared with TANK1-SODN and saline control groups. During the experiment we measured the tumor volume every 5 days with vernier calipers; observed the histopathological characteristics of tumor tissues under microscope; went further to detect the minute changing of ultrastructure of cancer cells by electron microscope; tested the expression levels of ki67 and hTERT protein by means of SABC immunohistochemical method; and detected the lung cancer cells＇ hTERT mRNA expression level by hybridization in situ （ISH） in each group. RESULTS After 16 days of continuous injection, the tumor volume in TANK1-ASODN group was significantly smaller than the other 2 groups （both P 〈 0.01）; quite a lot of tumor cell degeneration and necrosis were observed in mice given TANK1-ASODN. The results of electron microscope also showed that TANK1-ASODN has the power to kill cancer cells in various ways. Moreover, statistically *** decreases in the positive expression ratio of Ki67 Labeling Index （P 〈 0.01）, hTERT protein （P 〈 0.01）, and hTERT mRNA （P 〈 0.01） were consistently observed in the TANK1-ASODN group. CONCLUSION Human lung cancer cell line CALU expressed high telomerase activity. TANK1-ASODN had the ability to declin

关键词： TANK1-ASOND intratumoral injection CALU gene therapy

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Doxorubicin-loaded zein in situ gel for interstitial chemotherapy of colorectal cancer

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Acta Pharmaceutica Sinica B 2012年第6期2卷 610-614页

作者： Ning Shen Jie Hu Linan Zhang Li Zhang Yongjun Sun Yinghua Xie Shaomei Wu Lei Liu Zibin Gao Department of Pharmacy Hebei University of Science and TechnologyShijiazhuang 050018China Department of Immunology Hebei Medical UniversityShijiazhuang 050017China Department of Pharmaceutics New Drug Research and Development CenterNorth China Pharmaceutical Group CorporationShijiazhuang 050015China

The aim of this research was to evaluate doxorubicin(DOX)-loaded zein in situ gels,a new drug delivery system in which a liquid state drug can be transformed into semi-solid after intratumoral *** vitro release of DOX-loaded zein was investigated and the pharmacokinetics,biodistribution and therapeutic efficacy of these DOX-loaded zein formulations were investigated using BAI B/c nude tumor-bearing *** vitro release of DOX from the gels extended up to 7 *** accumulation of DOX in the tumor with lower drug concentration in blood and normal organs was obtained resulting in effective inhibition of tumor growth and fewer off-target side *** conclusion,a DOX-loaded in situ gel was developed with sustained release,enhanced anti-cancer efficacy for colorectal cancer in vivo,and especially with reduced off-target side effects.

关键词： Doxorubicin Zein In situ gel Tumor intratumoral injection

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