Cytosolic co-delivery of miRNA-34a and docetaxel with core-shell nanocarriers via caveolae-mediated pathway for the treatment of metastatic breast cancer

Zhang, Li; Yang, Xin; Lv, Yaqi; Xin, Xiaoqing; Qin, Chao; Han, Xiaoyan; Yang, Lei; He, Wei; Yin, Lifang

doi:10.1038/srep46186

Cited by 71 publications

(63 citation statements)

References 58 publications

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“…Nystatin and methyl‐β‐cyclodextrin (M‐CD) are two typical inhibitors for blocking caveolae internalization 15, 19. Therefore, the uptake in cells preincubated with these inhibitors was investigated.…”

Section: Resultsmentioning

confidence: 99%

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

et al. 2017

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Efficient microRNAs (miRNA) delivery into cells is a promising strategy for disease therapy, but is a major challenge because the available conventional nonviral vectors have significant drawbacks. In particular, after these vectors are entrapped in lysosomes, the escape efficiency of genes from lysosomes into the cytosol is less than 2%. Here, a novel approach for lethal‐7a (let‐7a) replacement therapy using rod‐shaped active pure drug nanoparticles (≈130 nm in length, PNPs) with a dramatically high drug‐loading of ≈300% as vectors is reported. Importantly, unlike other vectors, the developed PNPs/let‐7a complexes (≈178 nm, CNPs) can enter cells and bypass the lysosomal route to localize to the cytosol, achieving efficient intracellular delivery of let‐7a and a 50% reduction in expression of the target protein (KRAS). Also, CNPs prolong the t 1/2 of blood circulation by ≈threefold and increase tumor accumulation by ≈1.5–2‐fold, resulting in significantly improved antitumor efficacies. Additionally, no damage to normal organs is observed following systemic injection of CNPs. In conclusion, rod‐shaped active PNPs enable efficient and safe delivery of miRNA with synergistic treatment for disease. This nanoplatform would also offer a viable strategy for the potent delivery of proteins and peptides in vitro and in vivo.

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Section: Resultsmentioning

confidence: 99%

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

et al. 2017

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“…We investigated the cellular uptake using confocal laser scanning microscopy (CLSM), as previously described. 14 Briefly, we prepared TPP 111 -Cy5.5 (TPPc) nano-complexes with pGL-3 plasmid, as described above. We seeded 5x10 4 of A549 or H358 cells in chambered cell culture slides (Falcon, Corning, NY).…”

Section: Methodsmentioning

confidence: 99%

<p>Nucleic Acid Delivery with α-Tocopherol-Polyethyleneimine-Polyethylene Glycol Nanocarrier System</p>

Hossian

Jois

Jonnalagadda

et al. 2020

IJN

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Purpose Nucleic acid-based therapies are a promising therapeutic tool. The major obstacle in their clinical translation is their efficient delivery to the desired tissue. We developed a novel nanosized delivery system composed of conjugates of α-tocopherol, polyethyleneimine, and polyethylene glycol (TPP) to deliver nucleic acids. Methods We synthesized a panel of TPP molecules using different molecular weights of PEG and PEI and analyzed with various analytical approaches. The optimized version of TPP (TPP 111 - the 1:1:1 molecular ratio) was self-assembled in water to produce nanostructures and then evaluated in diversified in vitro and in vivo studies. Results Through a panel of synthesized molecules, TPP 111 conjugate components self-assembled in water, forming globular shaped nanostructures of ~90 nm, with high nucleic acid entrapment efficiency. The polymer had low cytotoxicity in vitro and protected nucleic acids from nucleases. Using a luciferase-expressing plasmid, TPP 111 -plasmid nano-complexes were rapidly up-taken by cancer cells in vitro and induced strong transfection, comparable to PEI. Colocalization of the nano-complexes and endosomes/lysosomes suggested an endosome-mediated uptake. Using a subcutaneous tumor model, intravenously injected nano-complexes preferentially accumulated to the tumor area over 24 h. Conclusion These results indicate that we successfully synthesized the TPP 111 nanocarrier system, which can deliver nucleic acids in vitro and in vivo and merits further evaluation.

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“…Therefore, it is important to elucidate the pathogenesis of breast cancer and develop new treatment strategies (14,15).…”

Section: Discussionmentioning

confidence: 99%

miR‑202 acts as a potential tumor suppressor in breast cancer

et al. 2018

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Abstract. Breast cancer affects ~10% of women worldwide and is responsible for ~12% of all cancer-associated mortalities. Breast cancer is more prone to metastasis compared with other types of cancer. Up to 5% of patients with breast cancer present with incurable metastasis and an additional 10-15% of patients develop metastases within 3 years of their initial diagnosis. MicroRNAs (miRNAs) are short RNAs, 21-25 nucleotides in length, that have been shown to significantly affect gene expression. In total >2,000 miRNAs have been identified and specific miRNAs have been revealed to be associated with cancer. In the present study, we observed that the majority of breast cancer specimens collected expressed low levels of miR-202 compared with adjacent tissues and normal cell lines. Mechanistic investigations identified KRAS as a potential target gene of miR-202 and it was demonstrated that miR-202 exerted its tumor-suppressive effects by regulating the expression of KRAS in breast cancer cells. Functional assays revealed that miR-202 significantly reduced cell proliferation, migration and invasion in vitro. In summary, these results indicate the function of miR-202 in breast cancer progression and suggest that its use within breast cancer therapy is promising. IntroductionBreast cancer is one of the most common malignant tumors in women. In many areas, breast cancer is the most common malignancy in females. In China, the incidence of breast cancer is increasing annually. Because the development and progression of breast cancer are complex processes involving many genes, the underlying mechanism of breast cancer remains unclear (1,2).Single-stranded RNAs consisting of 19 to 25 nucleotides are known as microRNAs (miRNAs). These RNAs are regulatory molecules that modulate the expression of functional genes, play an important role in many biological processes, and are expressed in a tissue-and time-specific manner. miRNAs regulate gene expression at the post-transcriptional level mainly via completely complementary or partially complementary binding to the 3' UTR of the target gene, resulting in degradation or translational repression of the target gene (2-4). Studies have shown that a variety of miRNAs are involved in malignant transformation processes, such as malignant proliferation, metastasis and recurrence, and apoptosis inhibition. Studies have reported that miRNA inhibitors can reduce the high miR-21 expression in breast cancer cells, inhibiting proliferation and migration; that miR-373 can promote the metastasis of breast cancer cells; that miR-520 plays a role in promoting the development of breast cancer; and that miR-126 and miR-335 are able to inhibit breast cancer to a certain extent (5-7). Recent studies have demonstrated that miR-202 is associated with several types of cancer, miR-202 has a lower expression in several of cancers, and however, the expression and function of miR-202 have not been investigated in breast cancer (8).KRAS belongs to the RAS family; it is located on the short arm of chromosome 1...

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Cytosolic co-delivery of miRNA-34a and docetaxel with core-shell nanocarriers via caveolae-mediated pathway for the treatment of metastatic breast cancer

Cited by 71 publications

References 58 publications

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

<p>Nucleic Acid Delivery with α-Tocopherol-Polyethyleneimine-Polyethylene Glycol Nanocarrier System</p>

miR‑202 acts as a potential tumor suppressor in breast cancer

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