Co-Delivery of 5-Fluorouracil and Paclitaxel in Mitochondria-Targeted KLA-Modified Liposomes to Improve Triple-Negative Breast Cancer Treatment

Chen, Tianyu; Chen, Hui; Jiang, Yichun; Yan, Qi; Zheng, Shuling; Wu, Min

doi:10.3390/ph15070881

Cited by 13 publications

(3 citation statements)

References 57 publications

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“…Du et al developed a novel brain-seeking breast carcinoma cell peptide (BRBP1) able to target the TWF1 -overexpressing triple-negative MDA-MB-231BR (or 231-BR) cell line. The peptide, BRBP1-TAT-KLA, is composed of i) the MDA-MB-231BR-targeting peptide BRBP1, ii) the pro-apoptotic KLA (acetyl-(KLAKLAK)2-NH2) peptide to target mitochondria and disrupt their membranes [ 361 ], and iii) the CPP TAT for enhanced cell penetration [ 362 ]. As MDA-MB-231BR cells are resistant to PTX, the team used the BRBP1-TAT-KLA-functionalized liposomes, dual-loaded with PTX and an siRNA to intefere with TWF1 gene expression, to resensitize the cells to PTX ( Fig.…”

Section: Targeted Nanoliposomes For Breast Cancer Treatmentmentioning

confidence: 99%

Functionalized liposomes for targeted breast cancer drug delivery

Nel

Elkhoury

Velot

et al. 2023

Bioactive Materials

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Section: Targeted Nanoliposomes For Breast Cancer Treatmentmentioning

confidence: 99%

Functionalized liposomes for targeted breast cancer drug delivery

Nel

Elkhoury

Velot

et al. 2023

Bioactive Materials

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“…Liposomes composed of natural phospholipids and cholesterol have been widely investigated as anti-cancer drug carriers for the delivery of hydrophobic drugs. Liposomes exhibit excellent biocompatibility and biodegradation, and drugs delivered by liposomes can accumulate at tumor sites due to their EPR effect. − Despite their excellent properties, applications of liposomes with a size smaller than 100 nm are often limited due to the poor stability caused by spontaneous fusion between liposomes, resulting in load loss and unsatisfactory mixing. A number of studies have been conducted by incorporating polyethylene glycol (PEG) into lipid vesicles to prevent engulfment by the mononuclear capture system and reticuloendothelial system, by which a longer circulation time can be achieved in the body.…”

Section: Introductionmentioning

confidence: 99%

Calcium Orthophosphate in Liposomes for Co-Delivery of Doxorubicin Hydrochloride/Paclitaxel in Breast Cancer

Chen

Guo

et al. 2023

Mol. Pharmaceutics

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Nanoparticles (NPs) show great advantages in cancer treatment by enabling controlled and targeted delivery of payloads to tumor sites through the enhanced permeability and retention (EPR) effect. In this study, highly effective pH-responsive and biodegradable calcium orthophosphate@liposomes (CaP@Lip) NPs with a diameter of 110 ± 20 nm were designed and fabricated. CaP@Lip NPs loaded with hydrophobic paclitaxel and hydrophilic doxorubicin hydrochloride achieved excellent drug loading efficiencies of 70 and 90%, respectively. Under physiological conditions, the obtained NPs are negatively charged. However, they switched to positively charged when exposed to weak acidic environments by which internalization can be promoted. Furthermore, the CaP@Lip NPs exhibit an obvious structural collapse under acid conditions (pH 5.5), which confirms their excellent biodegradability. The "proton expansion" effect in endosomes and the pH-responsiveness of the NPs facilitate the release of encapsulated drugs from individual channels. The effectiveness and safety of the drug delivery systems were demonstrated through in vitro and in vivo experiments, with a 76% inhibition of tumor growth. These findings highlight the high targeting ability of the drugloaded NPs to tumor sites through the EPR effect, effectively suppressing tumor growth and metastasis. By combining CaP NPs and liposomes, this study not only resolves the toxicity of CaP but also enhances the stability of liposomes. The CaP@Lip NPs developed in this study have significant implications for biomedical applications and inspire the development of intelligent and smart drug nanocarriers and release systems for clinical use.

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“… 24 In addition, MLS promotes cellular uptake by nano delivery systems (NDS), Improving the efficiency of suppression of TNBC in vitro and in vivo. 25 , 26 This is mainly because the six lysine residues in the MLS could be kept intact with the tumor cell membranes and mitochondria membranes by electrostatic attractions and hydrogen bonding to facilitate drugs internalization. 27 , 28 The nuclear localization sequence (NLS), CGGGPKKKRKVGG, represents a group of oligopeptides that containing short amino acid sequences.…”

Section: Introductionmentioning

confidence: 99%

Subcellular Organelle-Targeted Nanostructured Lipid Carriers for the Treatment of Metastatic Breast Cancer

Dang¹,

Xing²,

Jia³

et al. 2023

IJN

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Background Subcellular organelle targeted nano-formulations for cancer treatment are receiving increasing attention owing to their benefits of precise drug delivery, maximized therapeutic index, and reduced off-target side effects. The nucleus and mitochondria, as the main subcellular organelles, are the significant organelles responsible for maintaining cell operation and metabolism. They can be involved in many essential physiological and pathological processes such as cell proliferation, organism metabolism, intracellular transportation, and play a critical role in regulating cell biology. Meanwhile, breast cancer metastasis is one of the leading causes of death in breast cancer patients. With the development of nanotechnology, nanomaterials have been widely used in tumor therapy. Methods We designed a subcellular organelle targeted nanostructured lipid carriers (NLC) to deliver paclitaxel (PTX) and gambogic acid (GA) to tumor tissues. Results Due to the surface of NLC being modified by subcellular organelle targeted peptide, the PTX and GA co-loaded NLC can accurately release PTX and GA in tumor cells. This property makes NLC able to easy to enter tumor site and target the specific subcellular organelle. The modified NLC can efficiently inhibit the growth of 4T1 primary tumor and lung metastasis, which may be related to the down-regulation of matrix metalloproteinase-9 (MMP-9) and BCL-2 levels, up-regulation of E-cadherin level, and antagonized PTX-induced increase of C-C chemokine ligand 2 (CCL-2) levels by GA. Meanwhile, the synergistic anti-tumor effect of GA and PTX has also been verified in vitro and in vivo experiments. Conclusion The subcellular organelle targeted peptide modified PTX+GA multifunctional nano-drug delivery system has a good therapeutic effect on tumors, and this study provides significant insights into the role of different subcellular organelles in inhibiting tumor growth and metastasis and inspires researchers to develop highly effective cancer therapeutic strategies through subcellular organelle targeted drugs.

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Co-Delivery of 5-Fluorouracil and Paclitaxel in Mitochondria-Targeted KLA-Modified Liposomes to Improve Triple-Negative Breast Cancer Treatment

Cited by 13 publications

References 57 publications

Functionalized liposomes for targeted breast cancer drug delivery

Functionalized liposomes for targeted breast cancer drug delivery

Calcium Orthophosphate in Liposomes for Co-Delivery of Doxorubicin Hydrochloride/Paclitaxel in Breast Cancer

Subcellular Organelle-Targeted Nanostructured Lipid Carriers for the Treatment of Metastatic Breast Cancer

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