| Project/Area Number |
23K17213
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 90120:Biomaterials-related
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| Research Institution | Okayama University |
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Principal Investigator |
鄒 亜娟 岡山大学, 異分野融合先端研究コア, 特任助教 (80934588)
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| Project Period (FY) |
2023-04-01 – 2026-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2025: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2024: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Polyglycidol / pH-Responsive / Drug delivery |
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| Outline of Research at the Start |
A PG-based polymeric NP that can exert the functions of on-demand uptake and active motion in protein rich biofluids will be developed to precisely transport nanomedicine into solid tumors.
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| Outline of Annual Research Achievements |
Nanomaterial-based therapeutics are promising platforms for targeted cancer treatment. Nevertheless, during the blood circulation, nanomaterials tend to adsorb plasma proteins and consequently initiate macrophage uptake, which will in turn reduce the amounts of nanomaterials reaching to tumor sites. Although modifying nanomaterials with anti-biofouling surfaces can suppress non-specific interactions, these inert surfaces are unfavorable for targeted uptake. To overcome such dilemma, current research aims to develop a stimuli-responsive drug delivery system that can convert its surface property from bioinert in blood circulation to bioactive in tumor microenvironment, thus realizing the objective of simultaneously reducing non-specific uptake and enahnced tareget uptake.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
pH-responsive delivery systems were constructed by functionalizing polyglycerol grafted graphene oxide (GO-PG) with acid-liable amide bonds, in which with carboxyl groups facing outward. The delivery system is relative stable at normal pH7.4 to maintain a negative surface charge, and become positively charged at pH6.5 due to the cleavage of protecting groups. However, the charge conversion is dedicated by the initial density of amino groups on GO-PG; that is, the higher density of amino group, the faster conversion. Specially, the GO-PG bearing amino groups of 60 umol/g maintained low macrophage uptake till 48 h and induced high uptake by CT26 cancer cells at 96 h, which demonstrates high potential for targeted delivery in vivo.
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| Strategy for Future Research Activity |
Investigating the performance of pH-responsive delivery systems in model animals in vivo will be the main focus of next stage work. If good results could be obtained at this stage, the future research will be directed to fabricating delivery systems for subcellular-targeted therapy.
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