Cabazitaxel-loaded human serum albumin nanoparticles combined with TGFβ-1 siRNA lipid nanoparticles for the treatment of paclitaxel-resistant non-small cell lung cancer
Abstract Background In the current treatment of non-small cell lung cancer (NSCLC), traditional chemotherapy causes high toxicity, so it is necessary to develop safe chemical drug delivery vehicles clinically. Chemotherapy monotherapy is prone to drug resistance. Chemotherapy combined with other the...
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Cancer Nanotechnology |
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| Online Access: | https://doi.org/10.1186/s12645-023-00194-7 |
| _version_ | 1797769640722563072 |
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| author | Tiantian Tan Yuxin Feng Weimin Wang Rongrong Wang Liyan Yin Yiying Zeng Zhaowu Zeng Tian Xie |
| author_facet | Tiantian Tan Yuxin Feng Weimin Wang Rongrong Wang Liyan Yin Yiying Zeng Zhaowu Zeng Tian Xie |
| author_sort | Tiantian Tan |
| collection | DOAJ |
| description | Abstract Background In the current treatment of non-small cell lung cancer (NSCLC), traditional chemotherapy causes high toxicity, so it is necessary to develop safe chemical drug delivery vehicles clinically. Chemotherapy monotherapy is prone to drug resistance. Chemotherapy combined with other therapies such as nucleic acid drugs is an effective way to avoid drug resistance and the toxicity of continuous chemotherapy. In this study, chemotherapy and siRNA therapy were combined to treat paclitaxel-resistant NSCLC in order to increase efficacy and reduce toxicity. This study aims to develop a cabazitaxel-loaded human serum albumin nanoparticles (CTX-HSA-NPs) to improve the toxicity of traditional CTX-Tween 80 and increase targeting, and to develop a TGFβ-1 siRNA lipid Nanoparticles (TGFβ-1 siRNA LNP) combined with chemotherapy in the treatment of paclitaxel-resistant NSCLC. Results This study prepared CTX-HSA-NPs and TGFβ-1 siRNA LNP had small particle size, high encapsulation efficiency (EE). CTX-HSA-NPs lyophilized powder has high stability after dissolved. The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was 1.8 times lower than that of CTX-Tween. More importantly, the combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC in vivo and in vitro. The results of tumor immunohistochemistry showed that TGFβ-1 siRNA LNP significantly inhibited the expression of TGFβ-1, and compared with other groups, the expression of P-gp after low-dose CTX-HSA-NPs treatment was lower, which did not cause obvious drug resistance. Conclusions The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was lower than that of CTX-Tween. TGFβ-1 siRNA LNP can treat paclitaxel-resistant NSCLC by inhibiting the express of TGFβ-1 mRNA. The combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC. A combination therapy of chemotherapy and nucleic acid drugs could be an effective approach for treating paclitaxel-resistant NSCLC. |
| first_indexed | 2024-03-12T21:11:59Z |
| format | Article |
| id | doaj.art-71dd7f9497294a3bb00a427dc17361d9 |
| institution | Directory Open Access Journal |
| issn | 1868-6958 1868-6966 |
| language | English |
| last_indexed | 2024-03-12T21:11:59Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Nanotechnology |
| spelling | doaj.art-71dd7f9497294a3bb00a427dc17361d92023-07-30T11:07:32ZengBMCCancer Nanotechnology1868-69581868-69662023-07-0114113410.1186/s12645-023-00194-7Cabazitaxel-loaded human serum albumin nanoparticles combined with TGFβ-1 siRNA lipid nanoparticles for the treatment of paclitaxel-resistant non-small cell lung cancerTiantian Tan0Yuxin Feng1Weimin Wang2Rongrong Wang3Liyan Yin4Yiying Zeng5Zhaowu Zeng6Tian Xie7School of Pharmacy, Hangzhou Normal UniversitySchool of Pharmacy, Hangzhou Normal UniversitySchool of Pharmacy, Hangzhou Normal UniversitySchool of Pharmacy, Hangzhou Normal UniversityKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang ProvinceSchool of Pharmacy, Hangzhou Normal UniversitySchool of Pharmacy, Hangzhou Normal UniversitySchool of Pharmacy, Hangzhou Normal UniversityAbstract Background In the current treatment of non-small cell lung cancer (NSCLC), traditional chemotherapy causes high toxicity, so it is necessary to develop safe chemical drug delivery vehicles clinically. Chemotherapy monotherapy is prone to drug resistance. Chemotherapy combined with other therapies such as nucleic acid drugs is an effective way to avoid drug resistance and the toxicity of continuous chemotherapy. In this study, chemotherapy and siRNA therapy were combined to treat paclitaxel-resistant NSCLC in order to increase efficacy and reduce toxicity. This study aims to develop a cabazitaxel-loaded human serum albumin nanoparticles (CTX-HSA-NPs) to improve the toxicity of traditional CTX-Tween 80 and increase targeting, and to develop a TGFβ-1 siRNA lipid Nanoparticles (TGFβ-1 siRNA LNP) combined with chemotherapy in the treatment of paclitaxel-resistant NSCLC. Results This study prepared CTX-HSA-NPs and TGFβ-1 siRNA LNP had small particle size, high encapsulation efficiency (EE). CTX-HSA-NPs lyophilized powder has high stability after dissolved. The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was 1.8 times lower than that of CTX-Tween. More importantly, the combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC in vivo and in vitro. The results of tumor immunohistochemistry showed that TGFβ-1 siRNA LNP significantly inhibited the expression of TGFβ-1, and compared with other groups, the expression of P-gp after low-dose CTX-HSA-NPs treatment was lower, which did not cause obvious drug resistance. Conclusions The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was lower than that of CTX-Tween. TGFβ-1 siRNA LNP can treat paclitaxel-resistant NSCLC by inhibiting the express of TGFβ-1 mRNA. The combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC. A combination therapy of chemotherapy and nucleic acid drugs could be an effective approach for treating paclitaxel-resistant NSCLC.https://doi.org/10.1186/s12645-023-00194-7CabazitaxelAlbuminPaclitaxel-resistant NSCLCLipid nanoparticlesTGFβ-1 siRNA |
| spellingShingle | Tiantian Tan Yuxin Feng Weimin Wang Rongrong Wang Liyan Yin Yiying Zeng Zhaowu Zeng Tian Xie Cabazitaxel-loaded human serum albumin nanoparticles combined with TGFβ-1 siRNA lipid nanoparticles for the treatment of paclitaxel-resistant non-small cell lung cancer Cancer Nanotechnology Cabazitaxel Albumin Paclitaxel-resistant NSCLC Lipid nanoparticles TGFβ-1 siRNA |
| title | Cabazitaxel-loaded human serum albumin nanoparticles combined with TGFβ-1 siRNA lipid nanoparticles for the treatment of paclitaxel-resistant non-small cell lung cancer |
| title_full | Cabazitaxel-loaded human serum albumin nanoparticles combined with TGFβ-1 siRNA lipid nanoparticles for the treatment of paclitaxel-resistant non-small cell lung cancer |
| title_fullStr | Cabazitaxel-loaded human serum albumin nanoparticles combined with TGFβ-1 siRNA lipid nanoparticles for the treatment of paclitaxel-resistant non-small cell lung cancer |
| title_full_unstemmed | Cabazitaxel-loaded human serum albumin nanoparticles combined with TGFβ-1 siRNA lipid nanoparticles for the treatment of paclitaxel-resistant non-small cell lung cancer |
| title_short | Cabazitaxel-loaded human serum albumin nanoparticles combined with TGFβ-1 siRNA lipid nanoparticles for the treatment of paclitaxel-resistant non-small cell lung cancer |
| title_sort | cabazitaxel loaded human serum albumin nanoparticles combined with tgfβ 1 sirna lipid nanoparticles for the treatment of paclitaxel resistant non small cell lung cancer |
| topic | Cabazitaxel Albumin Paclitaxel-resistant NSCLC Lipid nanoparticles TGFβ-1 siRNA |
| url | https://doi.org/10.1186/s12645-023-00194-7 |
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