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Vasanthan Ravichandran,Thuy Giang Nguyen Cao,Dae Gun Choi,Han Chang Kang,Min Suk Shim 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.88 No.-
Combination therapy has gained great attraction as an effective strategy for the treatment of cancers. Inthis study, non-ionic polysorbate-based nanoparticles were prepared for combination chemo/photo-thermal/photodynamic cancer therapy via effective intracellular delivery of piperlongumine (PL) andindocyanine green (ICG). PL was used as a pro-oxidant drug that can induce selective apoptosis throughthe increase of oxidative stress in cancer cells. ICG was used as a near-infrared (NIR) light-absorbingphotothermal and photodynamic agent. Non-ionic Tween 80 (T80) polysorbate was used to prepare PLandICG-loaded micelles with nanoscale diameters. Both PL and ICG were efficiently encapsulated in theT80-based micelles. Storage stability of ICG in aqueous solutions was greatly improved by encapsulationinto the T80-based micelles. ICG-loaded T80 micelles (ICG-T80) showed higher photothermal conversionefficiency than free ICG. T80 also increased cellular uptake of ICG. Moreover, ICG-T80 showed NIR lighttriggeredreactive oxygen species (ROS) generation in MCF-7 human breast cancer cells, owing to thephotodynamic effects of NIR light-absorbing ICG. PL-loaded T80 micelles also increased intracellular ROSlevels in MCF-7 cells owing to the pro-oxidant activity of PL. In vitro study showed that ICG-T80 micellesexhibited efficient anticancer activity under NIR irradiation via combined photothermal therapy (PTT)and photodynamic therapy (PDT). PL- and ICG-loaded T80 micelles (PL-ICG-T80) further increased thecytotoxicity via combined chemo/PTT/PDT. PL-ICG-T80 also showed cancer-selective cytotoxicity. Thisstudy demonstrates that PL-ICG-T80 micelles are effective for NIR light-triggered combination chemo/PTT/PDT.
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.