&lt;p&gt;Multi-Stimuli-Responsive DOX Released from Magnetosome for Tumor Synergistic Theranostics&lt;/p&gt;

Tsai, Ming-Fong; Lo, Yu‐Lun; Huang, Yuan-Chun; Yu, Chia‐Li; Wu, Yi-Ting; Su, Chia‐Hao; Wang, Li Fang

doi:10.2147/ijn.s275655

Cited by 11 publications

(12 citation statements)

References 40 publications

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“…This system can present an external stimulus response, such as temperature or light, to control the cargo delivery. In contrast, another external stimulus or an internal one, such as acidic pH, high redox potential, elevated concentration of ROS, or high temperature in the tumoral tissues can synergistically activate and guide the nanostructures to the specific therapeutic zone [ 52 , 219 , 220 , 221 , 222 ]. Hence, considering the complexity and multi-step procedures involved in cancer therapy, “take out two targets with one shot” strategies would effectively trigger drugs with superior performance to single therapeutic strategies [ 223 ].…”

Section: Polymersomes For Stimuli-responsive Anticancer Therapeutic D...mentioning

confidence: 99%

Light-Triggered Polymersome-Based Anticancer Therapeutics Delivery

et al. 2022

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Polymersomes are biomimetic cell membrane-like model structures that are self-assembled stepwise from amphiphilic copolymers. These polymeric (nano)carriers have gained the scientific community’s attention due to their biocompatibility, versatility, and higher stability than liposomes. Their tunable properties, such as composition, size, shape, and surface functional groups, extend encapsulation possibilities to either hydrophilic or hydrophobic cargoes (or both) and their site-specific delivery. Besides, polymersomes can disassemble in response to different stimuli, including light, for controlling the “on-demand” release of cargo that may also respond to light as photosensitizers and plasmonic nanostructures. Thus, polymersomes can be spatiotemporally stimulated by light of a wide wavelength range, whose exogenous response may activate light-stimulable moieties, enhance the drug efficacy, decrease side effects, and, thus, be broadly employed in photoinduced therapy. This review describes current light-responsive polymersomes evaluated for anticancer therapy. It includes light-activable moieties’ features and polymersomes’ composition and release behavior, focusing on recent advances and applications in cancer therapy, current trends, and photosensitive polymersomes’ perspectives.

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Section: Polymersomes For Stimuli-responsive Anticancer Therapeutic D...mentioning

confidence: 99%

Light-Triggered Polymersome-Based Anticancer Therapeutics Delivery

et al. 2022

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“…tPF@PCM mainly accumulated in the liver and spleen, which is in line with other reports of nano-formulations. 45 , 46 Furthermore, there was a moderate aggregation of tPF@PCM at the tumor site, with the highest level observed at 24 h post-injection ( Figure S11 ), which reveals the ideal timing for the initiation of reliable tumor-targeting photothermal therapy.…”

Section: Resultsmentioning

confidence: 98%

Dual Targeting of Endoplasmic Reticulum by Redox-Deubiquitination Regulation for Cancer Therapy

Cai¹,

Hou²,

Zhang³

et al. 2021

IJN

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Background Recently, nanocatalyst-induced endoplasmic reticulum (ER) stress for cancer therapy has been attracting considerable attention. However, cancer cells are often able to overcome ER stress-induced death by activating the unfolded protein response (UPR), making nanocatalytic monotherapy a poor defense against cancer progression. Purpose In this study, to improve the nanocatalytic treatment efficacy, a phase change material (PCM) was used to encapsulate the upstream ER stress initiator, iron oxide nanoparticles (Fe 3 O 4 NPs), and the downstream UPR modulator, PR-619. Subsequently, the tumor-homing peptide tLyP-1 was coupled to it to form tLyP-1/PR-619/Fe 3 O 4 @PCM (tPF@PCM) theranostic platform. Materials and Methods tPF@PCM was synthesized using nanoprecipitation and resolidification methods followed by the EDC/NHS cross-linking method. The targeting capacity of tPF@PCM was evaluated in vitro and in vivo using flow cytometry and magnetic resonance imaging, respectively. The therapeutic efficacy of tPF@PCM was investigated in a renal cell carcinoma mouse model. Moreover, we explored the synergistic anti-tumor mechanism by examining the intracellular reactive oxygen species (ROS), aggregated proteins, ER stress response levels, and type of cell death. Results tPF@PCM had excellent tumor-targeting properties and exhibited satisfactory photothermal-enhanced tumor inhibition efficacy both in vitro and in vivo. Specifically, the phase transition temperature (45 °C) maintained using 808 nm laser irradiation significantly increased the release and catalytic activity of the peroxidase mimic Fe 3 O 4 NPs. This strongly catalyzed the generation of hydroxyl radicals (•OH) via the Fenton reaction in the acidic tumor microenvironment. The redox imbalance subsequently resulted in an increase in the level of damaged proteins in the ER and initiated ER stress. Moreover, the pan-deubiquitinase inhibitor PR-619 blocked the “adaptive” UPR-mediated degradation of these damaged proteins, exacerbating the ER burden. Consequently, irremediable ER stress activated the “terminal” UPR, leading to apoptosis in cancer cells. Conclusion This ER stress-exacerbating strategy effectively suppresses tumorigenesis, offering novel directions for advances in the treatment of conventional therapy-resistant cancers.

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“…2-Hydroxyethyl-2 -(bromoisobutyryl) ethyl disulfide (HO-SS-Br, 1) was synthesized according to previous publication [20]. The final product was purified by column chromatography with a 60-200 um silica column, and the eluent is 20% v/v ethyl acetate in hexane.…”

Section: Synthesis Of Mpeg-ss-br Macroinitiator (3)mentioning

confidence: 99%

Light- and Redox-Responsive Block Copolymers of mPEG-SS-ONBMA as a Smart Drug Delivery Carrier for Cancer Therapy

Fang

Chiu

et al. 2022

Pharmaceutics

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The development of stimuli-responsive polymeric micelles for targeted drug delivery has attracted much research interest in improving therapeutic outcomes. This study designs copolymers responsive to ultraviolet (UV) light and glutathione (GSH). A disulfide linkage is positioned between a hydrophilic poly(ethylene glycol) monomethyl ether (mPEG) and a hydrophobic o-nitrobenzyl methacrylate (ONBMA) to yield amphiphilic copolymers termed mPEG-SS-pONBMA. Three copolymers with different ONBMA lengths are synthesized and formulated into micelles. An increase in particle size and a decrease in critical micelle concentration go together with increasing ONBMA lengths. The ONB cleavage from mPEG-SS-pONBMA-formed micelles results in the transformation of hydrophobic cores into hydrophilic ones, accelerating drug release from the micelles. Obvious changes in morphology and molecular weight of micelles upon combinational treatments account for the dual-stimuli responsive property. Enhancement of a cell-killing effect is clearly observed in doxorubicin (DOX)-loaded micelles containing disulfide bonds compared with those containing dicarbon bonds upon UV light irradiation. Collectedly, the dual-stimuli-responsive mPEG-SS-pONBMA micelle is a better drug delivery carrier than the single-stimuli-responsive mPEG-CC-pONBMA micelle. After HT1080 cells were treated with the DOX-loaded micelles, the high expression levels of RIP-1 and MLKL indicate that the mechanism involved in cell death is mainly via the DOX-induced necroptosis pathway.

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<p>Multi-Stimuli-Responsive DOX Released from Magnetosome for Tumor Synergistic Theranostics</p>

Cited by 11 publications

References 40 publications

Light-Triggered Polymersome-Based Anticancer Therapeutics Delivery

Light-Triggered Polymersome-Based Anticancer Therapeutics Delivery

Dual Targeting of Endoplasmic Reticulum by Redox-Deubiquitination Regulation for Cancer Therapy

Light- and Redox-Responsive Block Copolymers of mPEG-SS-ONBMA as a Smart Drug Delivery Carrier for Cancer Therapy

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