Drug Delivery and Translational Research
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2021
·Vol. 12
·期 1
·167-179
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IF 4.617
Wang Shuanghu,Tan Xueying,Zhou Quan,Geng Peiwu,Wang Jinhui,Zou Ping,Deng Aiping,Hu Jingbo
Multidrug resistance (MDR) is considered as a critical limiting factor for the successful chemotherapy, which is mainly characterized by the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2. In this study, folate-targeted polymeric micellar carrier was successfully constructed to co-delivery of doxorubicin (DOX) and SIS3 (FA/DOX/SIS3 micelles), a specific Smad3 inhibitor which sensitizes ABCB1- and ABCG2-overexpressing cancer cells to chemotherapeutic agents. The ratio of DOX to SIS3 in polymeric micelles was determined based on the anti-tumor activity against resistant breast cells. In addition, FA/DOX/SIS3 micelles exhibited a much longer circulation time in blood and were preferentially accumulated in resistant tumor tissue. Pharmacodynamic studies showed that FA/DOX/SIS3 micelles possessed superior anti-tumor activity than other DOX-based treatments. Overall, FA/DOX/SIS3 micelles are a promising formulation for the synergistic treatment of drug-resistant tumor. Graphical abstract
研究领域:
肿瘤学
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药剂学
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化疗
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2021
·
IF 10.041
Siyu Chen,Xiaoying Wang,Minghui Lin,Yingke Hou,Mengbin Ding,Deping Kong,Haitao Sun,Qin Zhang,Jingchao Li,Quan Zhou
Natural killer (NK) cell-mediated immunotherapy has shown a great promise for treatments of tumors, while some strategies that can improve its therapeutic efficacy and reduce potential adverse events are highly desired. We herein report a pH-sensitive second near-infrared (NIR-II) photothermal liposomal nanocomplex for enhanced NK cell-based immunotherapy of breast cancer. Such nanocomplex (LNC DS ) consists of charge-transfer nanoparticles (CTN) with pH-sensitive NIR-II photothermal effect, deoxyribonuclease I (DNase I), NK cell stimulant (SIS3) and a surface coated thermal-responsive liposome shell. Upon 1064 nm laser irradiation, LNC DS generates mild heat in a controlled manner, which results in destruction of thermal-responsive liposome shell to allow on-demand release of stimulants and DNase I in tumor sites. The released DNase I not only kills cancer cells, but also induces immunogenic cell death (ICD), which synergizes with the action of the released SIS3 to promote activation of NK cells and cytotoxic T lymphocytes, contributing to enhanced therapeutic efficacy of immunotherapy. As a result, a single treatment of LNC DS upon NIR-II photoactivation greatly inhibits the growths of subcutaneously implanted primary and distant tumors in a breast cancer murine model, and even completely prevents lung metastasis. This study thus offers a photo-controlled drug delivery nanosystem for efficacy and precise NK cell-mediated immunotherapy of cancer.
研究领域:
癌症生物学
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纳米技术
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免疫学
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药学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Zi-Wen Qiu,Ying-Tao Zhong,Zhen-Ming Lu,Ni Yan,Ren-Jiang Kong,Jia-Qi Huang,Zhuo-Feng Li,Jun-Mei Nie,Runqing Li,Hong Cheng
Cancer-associated fibroblasts (CAFs) assist in breast cancer (BRCA) invasion and immune resistance by overproduction of extracellular matrix (ECM). Herein, we develop FPC@S, a photodynamic immunomodulator that targets the ECM, to improve the photodynamic immunotherapy for fibrotic BRCA. FPC@S combines a tumor ECM-targeting peptide, a photosensitizer (protoporphyrin IX) and an antifibrotic drug (SIS3). After anchoring to the ECM, FPC@S causes ECM remodeling and BRCA cell death by generating reactive oxygen species (ROS) in situ. Interestingly, the ROS-mediated ECM remodeling can normalize the tumor blood vessel to improve hypoxia and in turn facilitate more ROS production. Besides, upon the acidic tumor microenvironment, FPC@S will release SIS3 for reprograming CAFs to reduce their activity but not kill them, thus inhibiting fibrosis while preventing BRCA metastasis. The natural physical barrier formed by the dense ECM is consequently eliminated in fibrotic BRCA, allowing the drugs and immune cells to penetrate deep into tumors and have better efficacy. Furthermore, FPC@S can stimulate the immune system and effectively suppress primary, distant and metastatic tumors by combining with immune checkpoint blockade therapy. This study provides different insights for the development of fibrotic tumor targeted delivery systems and exploration of synergistic immunotherapeutic mechanisms against aggressive BRCA.
研究领域:
肿瘤学
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免疫治疗
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药理学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Miao Deng,Rong Guo,Shuya Zang,Jingdong Rao,Mengmeng Li,Xian Tang,Chunyu Xia,Man Li,Zhirong Zhang,Qin He
Natural killer (NK) cell-based immunotherapy presents a promising antitumor strategy and holds potential for combination with chemotherapy. However, the suppressed NK cell activity and poor tumor retention of therapeutics hinder the efficacy. To activate NK cell-based immuno–chemotherapy and enhance the tumor retention, we proposed a pH-responsive self-aggregated nanoparticle for the codelivery of chemotherapeutic doxorubicin (DOX) and the transforming growth factor-β (TGF-β)/Smad3 signaling pathway inhibitor SIS3. Polycaprolactone-poly(ethylene glycol) (PCL-PEG2000) micelles modified with dibenzylcyclooctyne (DBCO) or azido (N3) and coated with acid-cleavable PEG5000 were established. This nanoplatform, namely, M-DN@DOX/SIS3, could remain well dispersed in the neutral systemic circulation, while quickly respond to the acidic tumor microenvironment and intracellular lysosomes, triggering copper-free click reaction-mediated aggregation, leading to the increased tumor accumulation and reduced cellular efflux. In addition, the combination of DOX with SIS3 facilitated by the aggregation strategy resulted in potent inhibition of melanoma tumor growth and significantly increased NK cells, NK cell cytokines, and antitumor T cells in the tumor. Taken together, our study offered a new concept of applying copper-free click chemistry to achieve nanoparticle aggregation and enhance tumor retention, as well as a promising new combined tumor treatment approach of chemotherapy and immunotherapy.
研究领域:
癌症研究
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纳米技术
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免疫疗法
·
化疗
·
药学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）