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Quan Hoang Truong,Daeyong Lee,Thuy Giang Nguyen Cao,Yeu-Chun Kim,심민석 한국고분자학회 2021 한국고분자학회 학술대회 연구논문 초록집 Vol.46 No.2
The generation of reactive oxygen species (ROS) in cancer cells induces oxidative stress and has been utilized for cancer-specific therapy. Therefore, the development of ROS-responsive carriers carrying anticancer drugs into tumor sites is critical for cancer-specific therapy. Here, we fabricated an ROS-responsive poly(ethylene glycol)-poly(methionine) [PEG-P(Met)] integrated with piperlongumine (PL). The micelles containing hydrophobic PL into a P(Met) core were fabricated via self-assembly. Under ROS conditions, transformation from hydrophobic to hydrophilic stage of P(Met) occurred, leading to the disassembly of core-shell structure and PL release. PL-loaded PEG-P(Met) micelles [(PL-PEG-P(Met)] induced higher apoptosis in MCF-7 cells compared to free PL. Notably, PL-PEG-P(Met) micelles exhibited cancer-specific cytotoxicity in MCF-7 cells due to elevated intracellular ROS. In conclusion, ROS-responsive PEG-P(Met) micelles find significant potential for cancer-selective therapy.
Guanidinium-Incorporated Micelleplexes for Low Toxic and Efficient siRNA Delivery
Quan Truong Hoang,허태영,최대건,최수형,심민석 한국고분자학회 2020 Macromolecular Research Vol.28 No.12
Small interfering RNA (siRNA)-based therapy has emerged as a powerful therapeutic tool due to its target-specific gene silencing. However, the therapeutic efficacy has been limited by poor cellular uptake, and therefore delivery vehicles are required to improve the cellular uptake. Herein, guanidinium-incorporated polyether- based block copolyelectrolytes were developed for improved cellular uptake and consequently increased gene silencing efficiency. Guanidinium-functionalized poly(ethylene oxide-b-allyl glycidyl ether) (G-PEO-PAGE) were prepared by living anionic ring opening polymerization of allyl glycidyl ether and post-modification to introduce guanidinium groups. G-PEO-PAGE provides efficient complexation with siRNA due to highly cationic charges of the guanidinium groups at physiological pH, resulting in significantly improved cellular uptake of siRNA and consequently increased gene silencing efficiency. In addition, G-PEO-PAGE showed significantly lower cytotoxicity compared to branched polyethylenimine as a commercial counterpart. This study demonstrates that guanidinium-incorporated block copolyelectrolytes have a great potential for efficient and low toxic siRNA delivery.
Quan Truong Hoang,이대용,최대건,김유천,심민석 한국공업화학회 2021 Journal of Industrial and Engineering Chemistry Vol.95 No.-
High levels of intracellular reactive oxygen species (ROS) in cancer cells have emerged as a cancer-specificstimulus that can be utilized for anticancer therapy. Therefore, ROS-responsive drug carriers haveattracted considerable attention as cancer-specific drug delivery systems. In this study, an ROS-responsive poly(ethylene glycol)-poly(methionine) [PEG-P(Met)] was synthesized to achieve safe andeffective delivery of piperlongumine (PL), a pro-oxidant drug, into cancer cells. Nanoscale core–shellmicelles encapsulating hydrophobic PL into a P(Met) core were prepared by self-assembling. Theincreased ROS levels in cancer cells triggered a hydrophobic-to-hydrophilic transition of the polypeptide,which led to the ROS-responsive disassembly of the micelles and consequently efficient PL release intocancer cells. Compared to free PL, PL-loaded PEG-P(Met) [(PL-PEG-P(Met)] micelles exhibited enhancedapoptosis in MCF-7 human breast cancer cells owing to the efficient intracellular delivery of PL. Notably,the PL-PEG-P(Met) micelles exhibited cancer-specific cytotoxicity in MCF-7 human breast cancer cellsowing to a considerable increase in intracellular ROS level in the cells. These results demonstrate that theROS-responsive PEG-P(Met)-based micelles are safe and effective drug carriers for intracellular deliveryof PL, which can provide cancer-selective pro-oxidant therapy.
허태영,Quan Truong Hoang,Thuy Giang Nguyen Cao,오승환,유문철,심민석,최수형 한국생물공학회 2022 Biotechnology and Bioprocess Engineering Vol.27 No.6
RNAi-based therapeutics utilizing small interfering RNAs (siRNAs) are of significance in the clinic as it serves great potentials for gene-based treatment of human diseases. Currently, siRNA-based RNAi efficiency has been limited by facile degradation, poor cell membrane penetration, and short half-life time of siRNA. In this study, block copolyelectrolytes containing a poly(ethylene oxide) (PEO) neutral block and a cationic block were synthesized by anionic polymerization and post-polymerization modification. In the cationic block, guanidinium and ammonium groups were randomly incorporated with various fractions to achieve micelleplexes for safe and efficient siRNA delivery. Compared to traditional polyethylenimine-based polyplexes, all micelleplexes exhibited enhanced cellular internalization and better gene silencing efficiency with higher stability. As the fraction of guanidinium groups increased, the uptake level and siRNA transfection were enhanced due to stronger binding of guanidinium groups with siRNA. However, the trade-off between cellular internalization and toxicity was inevitable with increasing guanidinium fraction. The fraction of guanidinium group in block copolyelectrolytes was optimized by the systemic evaluation of cytotoxicity and gene silencing efficiency of the micelleplexes.
Vasanthan Ravichandran,Quan Truong Hoang,Thuy Giang Nguyen Cao,심민석 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.114 No.-
Sonodynamic therapy (SDT) has emerged as a promising noninvasive therapeutic modality due to itsdeep tissue penetration depth. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanocapsulesencapsulating oxygen-deficient MnWOx nanoparticles (NPs) and doxorubicin (DOX) were fabricatedfor chemo-sonodynamic combination therapy against cancer. To achieve cancer-targeted chemo-SDT,PLGA was conjugated to a cancer-targeting biotin through poly(ethylene glycol) (PEG). Biotin-PEG-PLGA (BP-PLGA) nanocapsules encapsulating DOX and hydrophobic MnWOx NPs(BP-PLGA-DOX@MnWOx) exhibited high physiological stability and pH-responsive drug release. Theoxygen-deficient MnWOx NPs enabled US-triggered generation of singlet oxygen and hydroxyl radicalsowing to their oxygen-deficient structures that prevent electron–hole recombination. Glutathione(GSH) depletion by MnWOx-loaded PLGA nanocapsules was observed in MCF-7 human breast cancercells, which leads to augmented intracellular ROS levels and sonodynamic effects. Notably,BP-PLGA-DOX@MnWOx greatly improved cellular uptake by breast cancer cells, resulting in efficientintracellular delivery of DOX and MnWOx NPs. As a result, BP-PLGA-DOX@MnWOx exhibited efficientand cancer-targeted cytotoxicity in MCF-7 cells upon US irradiation. This study demonstrates that BPPLGA-DOX@MnWOx nanocapsules are promising cancer-targeting nanosonosensitizers for efficientchemo-sonodynamic cancer therapy.