News of Biomaterials & Drug Controlled Release Laboratory
實驗室新聞
2024 恭喜碩士研究生 Manoj Kandel 畢業
2023 邱信程教授在ISOMRM&BCRS上發表主題演講：Semiconductor Nanotheranostic Systems: A Panacea Tool for Cancer Treatment
2023 Arjun Sabu 在美國拉斯維加斯舉行的國際會議「CRS 2023」上展示其博士研究成果
2023 Manoj Kandel 在日本札幌舉行的生物材料國際會議上就其碩士研究發表了口頭報告
2023 Arjun Sabu 和 Manoj Kandel 在台灣淡水的「ISOMRM&BCRS 2023」上就其研究成果進行口頭報告
2023 Arjun Sabu 榮獲原科院專題研究海報競賽 傑出海報獎
2023 Manoj Kandel 榮獲原科院專題研究海報競賽 最佳海報獎
2023 Manoj Kandel 榮獲 ISOMRM&BCRS 榮譽提名
2021 余亭葦、沈名吟、邱信程榮獲 the 8th Asian Biomaterials Congress 最佳海報獎(唯一)
2021 博士班研究生Reesha Kv榮獲2021中華民國生醫材料及藥物制放研討會特優海報獎
2021 邱信程教授榮獲109年度科技部傑出研究獎
2020 邱信程教授榮任中華民國生醫材料與藥物制放學會理事長(任期二年)
成果發表
Microfluidized Dextran Microgels Loaded with Cisplatin/SPION Lipid Nanotherapeutics for Local Colon Cancer Treatment via Oral Administration
Journal of Advanced Healthcare Materials, Volume11, Issue20, October 19, 2022, 2270120
I-Lin Lu, Ting-Wei Yu, Te-I Liu , Hsin-Hung Chen, Ying-Chieh Yang, Chun-Liang Lo, Chi-Ya Wang, Hsin-Cheng Chiu
Abstract
Multifunctional sequential targeted delivery system is developed as an efficient therapeutic strategy against malignant tumors with selective accumulation and minimal systemic drug absorption. The therapeutic system is comprised of microfluidized dextran microgels encapsulating cisplatin/superparamagnetic iron oxide nanoparticles (SPIONs)-loaded trilaurin-based lipid nanoparticles (LNPs). The microgel system is imparted hierarchically dual targeting via dextran and folic acid (FA) residues, leading to increases both in retention of the microgels in colon and in cellular uptake of the therapeutic LNPs by colon cancer cells while being used for oral therapeutic delivery. Encapsulation of the therapeutic LNPs into dextran microgels attained by microfluidized crosslinking reaction reduces gastrointestinal adhesion and prevents the FA-modified LNPs from cellular transport by proton-coupled FA transporters in small intestine during their oral delivery to colon. Upon enzymatic degradation of the dextran microgels by dextranase present exclusively in colon, LNPs thus released become more recognizable and readily internalized by FA receptor-overexpressing colon cancer cells. The combined chemo/magnetothermal therapeutic effect of dual targeted lipid nanoparticle-loaded microgels from entrapped lipidized cisplatin and alternating magnetic field-treated SPIONs significantly inhibits tumor growth and suppresses metastatic peritoneal carcinomatosis in orthotopic colon cancer-bearing mice.
Nanomedicines Targeting Glioma Stem Cells
Journal of ACS Appl. Mater. Interfaces 2023, 15, 1, 158–181, May 11, 2022
Arjun Sabu, Te-I Liu, Siew Suan Ng, Ruey-An Doong, Yu-Fen Huang*, and Hsin-Cheng Chiu*
Abstract
Glioblastoma (GBM), classified as a grade IV glioma, is a rapidly growing, aggressive, and most commonly occurring tumor of the central nervous system. Despite the therapeutic advances, it carries an ominous prognosis, with a median survival of 14.6 months after diagnosis. Accumulating evidence suggests that cancer stem cells in GBM, termed glioma stem cells (GSCs), play a crucial role in tumor propagation, treatment resistance, and tumor recurrence. GSCs, possessing the capacity for self-renewal and multilineage differentiation, are responsible for tumor growth and heterogeneity, leading to primary obstacles to current cancer therapy. In this respect, increasing efforts have been devoted to the development of anti-GSC strategies based on targeting GSC surface markers, blockage of essential signaling pathways of GSCs, and manipulating the tumor microenvironment (GSC niches). In this review, we will discuss the research knowledge regarding GSC-based therapy and the underlying mechanisms for the treatment of GBM. Given the rapid progression in nanotechnology, innovative nanomedicines developed for GSC targeting will also be highlighted from the perspective of rationale, advantages, and limitations. The goal of this review is to provide broader understanding and key considerations toward the future direction of GSC-based nanotheranostics to fight against GBM.
Alendronate/folic acid-decorated polymeric nanoparticles for hierarchically targetable chemotherapy against bone metastatic breast cancer
Journal of Materials Chemistry B, volume 8, Number 17,7 May 2020
Shih-Hong Chen, Te-I Liu, Cheng-Lin Chuang , Hsin-Hung Chen , Wen-Hsuan Chiang and Hsin-Cheng Chiu
Abstract
To considerably enhance treatment efficacy for bone metastatic breast cancer via dual bone/tumor-targeted chemotherapy, a nanoparticle-based delivery system comprising poly(lactic-co-glycolic acid) (PLGA) as the hydrophobic core coated with alendronate-modified D-α-tocopheryl polyethylene glycol succinate (ALN-TPGS) and folic acid-conjugated TPGS (FA-TPGS) was developed as a vehicle for paclitaxel (PTX) in this work. The ALN/FA-decorated nanoparticles not only showed superior ALN-mediated binding affinity for hydroxyapatite abundant in bone tissue but also promoted uptake of payloads by folate receptor-overexpressing cancer cells to significantly augment PTX cytotoxicity. Notably, through dual-targetable delivery to the bone matrix and folate receptor-overexpressing 4T1 tumors, the PTX-loaded nanoparticles substantially accumulated in bone metastases in vivo and inhibited 4T1 tumor growth and lung metastasis, leading to significant improvement of the survival rate of treated mice. Upon treatment with the ALN/FA-decorated PTX-loaded nanoparticles, the bone destruction and bone loss of the tumor-bearing mice were appreciably retarded, and the adverse effects on normal tissues were alleviated. These results demonstrate that the ALN/FA-decorated PTX-loaded delivery system developed in this study shows great promise for the effective treatment of bone metastatic breast cancer.
Prospects of an engineered tumor-targeted nanotheranostic platform based on NIR-responsive upconversion nanoparticles
Journal of Materials Advances, Volume 2, Number 22, 21 November 2021
Arjun Sabu, Jui-Yen Lin, Ruey-An Doong, Yu-Fen Huang and Hsin-Cheng Chiu
Abstract
Theranostics, which affords both therapeutic and diagnostic functions within a single entity, has emerged as a cutting-edge technology for the development of personalized nanomedicine. Nanoparticles also offer the potential to unlock new avenues in cancer theranostics, attributed to their capacity for multifunctionality and multivalency. Lanthanide-doped upconversion nanoparticles (UCNPs) constitute a promising nano-scale platform notable for its unique ability to convert near-infrared (NIR) light into higher-energy luminescence. In addition to the large anti-Stokes shift, UCNPs also feature multiple sharp emission peaks varying from the ultraviolet (UV) to the NIR region, long luminescence lifespan, and high stability against photobleaching. By using NIR irradiation as an excition source, UCNPs enable deep-tissue bioimaging, controlled cargo release and subsequent therapeutic actions with high spatial and temporal resolution. On the other hand, to accomplish site-specific targetability to maximize theranostic outcomes, active targeting directed by specific tumor-homing ligands has been proven to be efficacious in improving tumor accumulation and reducing side effects. The choice of targeting ligands falls into several general classes including small molecules, peptides, proteins, antibodies, carbohydrates, or nucleic acid aptamers. Ligand-mediated targeting of functionalized UCNPs tailored with cancer-specific recognition moieties will lead to enhanced cellular uptake and permeability in tumor tissues, thus achieving effective theranostic treatments and long-term prognosis. In this perspective, we discuss the provision and prospects of specific ligand functionalized UCNPs for targeted delivery and theranostic application in various types of tumor therapies.
Tumor microenvironment-responsive and oxygen self-sufficient oil droplet nanoparticles for enhanced photothermal/photodynamic combination therapy against hypoxic tumors
Journal of Controlled Release, 10 December 2020.
Reesha Kv, Te-I Liu, I.-Lin Lu, Chia-Chen Liu, Hsin-Hung Chen, Ting-Yu Lu, Wen-Hsuan Chiang,
Hsin-Cheng Chiu*
Abstract
The combination of photothermal and photodynamic therapy (PTT/PDT) shows pronounced potential as a prominent therapeutic strategy for tumor treatment. However, the efficacy is limited by insufficient tumor-targeted delivery of PTT and PDT reagents and the hypoxic nature of the tumor microenvironment. To overcome these limitations, tumor acidity-responsive lipid membrane-enclosed perfluorooctyl bromide oil droplet nanoparticles (NPs) surface modified with N-acetyl histidine-modified D-α-tocopheryl polyethylene glycol 1000 succinate (PFOB@IMHNPs) were developed, capable of co-delivering oxygen, IR780 (a photothermal agent) and mTHPC (a photodynamic sensitizer) into tumors. Through self-sufficient oxygen transportation in combination with promotion of cellular uptake upon acid-triggered generation of surface positive charge, the PFOB@IMHNPs effectively delivered IR780 and mTHPC and produced singlet oxygen within hypoxic TRAMP-C1 cells following exposure to irradiation at 660 nm. This led to effective killing of hypoxic cancer cells in vitro. Importantly, when irradiation at 808 and 660 nm was carried out, PT/PD combination therapy utilizing PFOB@IMHNPs dramatically suppressed the growth of TRAMP-C1 tumors through effective tumor-targeted cargo delivery and relief of tumor hypoxia. Our results suggest the high potential of the PFOB@IMHNPs developed in this study in clinical application for cancer treatment.
New combination treatment from ROS-Induced sensitized radiotherapy with nanophototherapeutics to fully eradicate orthotopic breast cancer and inhibit metastasis
Te-I Liu, Ting-Yu Lu, Ying-Chieh Yang, Siou-Han Chang, Hsin-Hung Chen, I.-Lin Lu, Arjun Sabu, Hsin-Cheng Chiu*
Abstract
Radiotherapy (RT) is one of the most commonly employed approaches in the treatment of malignant tumors and is often combined with radiosensitizers to enhance the therapeutic efficacy for clinical use. For developing a smart therapeutic strategy leveraging local tissue response to photo-mediated reactions and the combination of multiple treatment modalities involving ROS-induced sensitization of RT, a novel nanophototherapeutic system has been developed. The nanotherapeutics prepared from the assembly of poly (thiodiethylene malonate) (PSDEM) and PEG-PSDEM-PEG and loaded with suberoylanilide hydroxamic acid (SAHA) employed as the RT sensitizer and indocyanine green (ICG) as the photothermal/photodynamic agent, demonstrated the capability of undergoing structural change and releasing therapeutic payloads in response to near-infrared irradiation and X-ray radiotherapy. With highly localized and controllable reactions within the tumor site, the reactive oxygen species (ROS)-triggered SAHA unloading and the hyperthermia-induced vascular permeability of oxygen led to a significant sensitization of the target tissue in RT, which, in turn, led to the promotion of therapeutic effect in conjunction with photodynamic/photothermal therapies (PDT/PTT). In vitro studies demonstrated the damage in intracellular DNA double strands and the inhibition of cell proliferation in 4T1 breast cancer cells treated with ROS-induced sensitized RT. A substantial reduction in cell viability was also observed owing to the effects of the combination of photo-mediated treatments with sensitized RT compared to the effects of RT administration alone. Complete eradication of the primary tumor and the inhibition of lung metastasis was observed in five of six orthotopic 4T1 breast cancer-bearing mice subjected to combined PDT/PTT in nanophototherapeutics with ROS-induced sensitized RT at a low dosage (6 Gy), leading to the prominent survival fraction of ca. 83% over 60 days.
Dual stimuli-guided lipid-based delivery system of cancer combination therapy
Journal of Controlled Release, February 2020.
Te-I Liu, Ting-Yu Lu, Siou-Han Chang, Ming-Yin Shen, Hsin-Cheng Chiu*
Abstract
The combination therapy, as an emerging strategy for improved clinical efficacy of cancer therapy, may not achieve effective response owing to the lack of highly selective and efficient tumor targeting. Herein, a dual stimuli-guided chemo/magnetothermal combination therapy system based upon histamine dodecyl carbamate (HDC)-coated doxorubicin (DOX)/magnetite-loaded solid lipid nanoparticles (SLNs) was developed for enhanced anticancer effects. Taking advantage of the dual pHe-induced electrostatic and magnetic guidance, the in vitro cellular uptake of these functionalized SLNs by TRAMP-C1 cancer cells was highly enhanced, leading to remarkably increased anticancer ability. With the highly selective delivery of the therapeutics toward tumor via the dual stimuli-mediated guidance, the effective growth inhibition of tumors with the small initial size (ca 50 mm3) by only chemotherapy was observed whereas the combination therapy was essentially required to fully inhibit the growth of large tumors (200 mm3). The IHC staining of tumor tissue sections with the combination therapy against large tumors showed the appreciable increase of tumor cell apoptosis and reduction of tumor angiogenesis. The results suggest that the dual stimuli-guided combination therapy system developed herein be prominent in fully inhibiting tumor growth even with the solid tumors of large size at the onset of the treatment.
Hierarchically targetable polysaccharide-coated solid lipid nanoparticles as an oral chemo/thermotherapy delivery system for local treatment of colon cancer
Ming-Yin Shen, Te-I Liu, Ting-Wei Yu, Reesha Kv, Wen-Hsuan Chiang, Yuan-Chung Tsai, Hsin-Hung Chen, Sung-ChyrLin, Hsin-Cheng Chiu*
Abstract
Although oral formulations of anticancer chemotherapies are clinically available, the therapeutic action relies mostly on drug absorption, being inevitably accompanied with systemic side effects. It is thus desirable to develop oral therapy systems for the local treatment of colon cancers featured with highly selective delivery to cancer cells and minimized systemic drug absorption. The present study demonstrates the effective accumulation and cell uptake of the doxorubicin and superparamagnetic iron oxide nanoparticles-loaded solid lipid nanoparticle (SLN) delivery system for chemo/magnetothermal combination therapy at tumors by hierarchical targeting of folate (FA) and dextran coated on SLN surfaces in a sequential layer-by-layer manner. Both the in vitro and in vivo characterizations strongly confirmed that the dextran shells on SLN surfaces not only retarded the cellular transport of the FA-coated SLNs by the proton-coupled FA transporter on brush border membranes in small intestine, but also enhanced the particle residence in colon by specific association with dextranase. The enzymatic degradation and removal of dextran coating led to the exposure of the FA residues, thereby further facilitating the cellular-level targeting and uptake of the SLNs by the receptor-mediated endocytosis. The evaluation of the in vivo antitumor efficacy of the hierarchically targetable SLN therapy system by oral administration showed the effective inhibition of primary colon tumors and peritoneal metastasis in terms of the ascites volume and tumor nodule number and size, along with the absence of systemic side effects.
徵才
本研究團隊從事多功能生醫材料與智慧型治療傳遞系統的開發，所從事研究計畫具有高度創新與新穎性，並與國際相關學術研究密切結合，若您對生醫藥物奈米載體開發、細胞及動物活體藥物傳輸或相關研究有興趣者，非常歡迎您加入我們的研究陣容，包括研究助理、碩士班及博士班研究生和博士後研究員，聯絡請洽邱信程老師 (hscchiu@mx.nthu.edu.tw)。