Nucleus-selective codelivery of proteins and drugs for synergistic antitumor therapy

Yang, Lan; Ma, Huijie; Lin, Shuo; Zhu, Yupeng; Chen, Hui; Zhang, Ning; Feng, Xuli

doi:10.1039/d2sc03861g

Cited by 7 publications

(5 citation statements)

References 41 publications

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“…43 Two control experiments are carried out to study the endocytosis of the nanorod and spherical polymer brushes: (i) incubation of polymer nano-objects at 37 and 4 °C so that the ATP energy-assisted endocytosis across the cell membranes could be traced and (ii) pretreating the cells at 37 °C with NaN 3 which is a well-known electron transport inhibitor for ATP synthase. 60 This second experiment affects the ATP-driven uptake mechanism; thus, it would indirectly diminish the uptake of the nano-objects. Temperaturedependent cellular uptake of the polymer brush was carried out in the WT-MEF cell line at 37 and 4 °C, and the CLSM images are reported in Figure 7f (see Figure S25 for spherical brush P-Tyr-PEG-5000+DOX).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Polymer nanoparticles are typically endocytosed across the cell membrane at 37 °C, i.e., at the biological temperature by ATP-assisted energy-driven transportation pathways . Two control experiments are carried out to study the endocytosis of the nanorod and spherical polymer brushes: (i) incubation of polymer nano-objects at 37 and 4 °C so that the ATP energy-assisted endocytosis across the cell membranes could be traced and (ii) pretreating the cells at 37 °C with NaN 3 which is a well-known electron transport inhibitor for ATP synthase . This second experiment affects the ATP-driven uptake mechanism; thus, it would indirectly diminish the uptake of the nano-objects.…”

Section: Resultsmentioning

confidence: 99%

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Size- and Shape-controlled Biodegradable Polymer Brushes Based on l-Amino Acid for Intracellular Drug Delivery and Deep-Tissue Penetration

Gavhane,

Joshi,

Jayakannan

2024

Biomacromolecules

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We report size-and shape-controlled polymer brushes based on L-amino acid bioresource and study the role of polymer topology on the enzymatic biodegradation and deep-tissue penetration under in vitro and in vivo. For this purpose, Ltyrosine-based propargyl-functionalized monomer is tailor-made and polymerized via solvent-free melt polycondensation strategy to yield hydrophobic and clickable biodegradable poly(ester-urethane)s. Postpolymerization click chemistry strategy is applied to make well-defined amphiphilic one-dimensional rodlike and three-dimensional spherical polymer brushes by merely varying the lengths of PEG-azides in the reaction. These core−shell polymer brushes are found to be nontoxic and nonhemolytic and capable of loading clinical anticancer drug doxorubicin and deep-tissue penetrable near-infrared biomarker IR-780. In vitro enzymatic drug-release kinetics and lysotracker-assisted real-time live-cell confocal bioimaging revealed that the rodlike polymer brush is superior than its spherical counterparts for faster cellular uptake and enzymatic biodegradation at the endolysosomal compartments to release DOX at the nucleus. Further, in vivo live-animal bioimaging by IVIS technique established that the IR-780-loaded rodlike polymer brush exhibited efficient deep-tissue penetration ability and emphasized the importance of polymer brush topology control for biological activity. Polymer brushes exhibit good stability in the blood plasma for more than 72 h, they predominately accumulate in the digestive organs like liver and kidney, and they are less toxic to heart and brain tissues. IVIS imaging of cryotome tissue slices of organs confirmed the deep-penetrating ability of the polymer brushes. The present investigation opens opportunity for bioderived and biodegradable polymer brushes as next-generation smart drug-delivery scaffolds.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Size- and Shape-controlled Biodegradable Polymer Brushes Based on l-Amino Acid for Intracellular Drug Delivery and Deep-Tissue Penetration

Gavhane,

Joshi,

Jayakannan

2024

Biomacromolecules

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“…In another work, we prepared a simple amphiphilic nanocarrier (LC) with rapid endosomal escape ability for nuclear-selective delivery of the hydrophilic active protein DNase I and the hydrophobic anticancer drug DOX. 129 This multi-component nanoplatform is able to rapidly escape from the endolysosomes into the cytoplasm, allowing DNase I and DOX to aggregate in large numbers within the nucleus, thereby inducing powerful synergistic anti-cancer effects in vivo and in vitro (Fig. 8d).…”

Section: Nls Mediated Nucleus-targeted Therapymentioning

confidence: 99%

Research progress in nucleus-targeted tumor therapy

Chen,

Cao,

Xiang

et al. 2023

Biomater. Sci.

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“…Precise delivery of anti-cancer drugs based on nano-drug delivery systems to subcellular targets, such as mitochondria, lysosomes, and nuclei, has already been considered as an excellent cancer treatment strategy ( Yang L. et al, 2022 ; Zhang J. et al, 2022 ; Wang et al, 2022 ). Mitochondria, the powerhouse of aerobic metabolism, exert an essential role in cellular physiological and pathological processes ( Song et al, 2019 ; Zhang S. et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress induced by berberine-based mitochondria-targeted low temperature photothermal therapy

Song

Yang

et al. 2023

Front. Chem.

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Introduction: Mitochondria-targeted low-temperature photothermal therapy (LPTT) is a promising strategy that could maximize anticancer effects and overcome tumor thermal resistance. However, the successful synthesis of mitochondria-targeted nanodrug delivery system for LPTT still faces diverse challenges, such as laborious preparations processes, low drug-loading, and significant systemic toxicity from the carriers.Methods: In this study, we used the tumor-targeting folic acid (FA) and mitochondria-targeting berberine (BBR) derivatives (BD) co-modified polyethylene glycol (PEG)-decorated graphene oxide (GO) to synthesize a novel mitochondria-targeting nanocomposite (GO-PEG-FA/BD), which can effectively accumulate in mitochondria of the osteosarcoma (OS) cells and achieve enhanced mitochondria-targeted LPTT effects with minimal cell toxicity. The mitochondria-targeted LPTT effects were validated both in vitro and vivo.Results:In vitro experiments, the nanocomposites (GO-PEG-FA/BD) could eliminate membrane potential (ΔΨm), deprive the ATP of cancer cells, and increase the levels of reactive oxygen species (ROS), which ultimately induce oxidative stress damage. Furthermore, in vivo results showed that the enhanced mitochondria-targeted LPTT could exert an excellent anti-cancer effect with minimal toxicity.Discussion: Taken together, this study provides a practicable strategy to develop an ingenious nanoplatform for cancer synergetic therapy via mitochondria-targeted LPTT, which hold enormous potential for future clinical translation.

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Nucleus-selective codelivery of proteins and drugs for synergistic antitumor therapy

Abstract: An efficient nucleus-targeted co-delivery nanoplatform with high endosomal escape ability to transport proteins and drugs into nucleus was prepared for synergistically enhanced cancer therapy.

Cited by 7 publications

References 41 publications

Size- and Shape-controlled Biodegradable Polymer Brushes Based on l-Amino Acid for Intracellular Drug Delivery and Deep-Tissue Penetration

Size- and Shape-controlled Biodegradable Polymer Brushes Based on l-Amino Acid for Intracellular Drug Delivery and Deep-Tissue Penetration

Research progress in nucleus-targeted tumor therapy

Oxidative stress induced by berberine-based mitochondria-targeted low temperature photothermal therapy

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