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双敏化抗耐药纳米颗粒通过诱导细胞凋亡治疗难治性乳腺癌。

Dual Sensitization Anti-Resistant Nanoparticles for Treating Refractory Breast Cancers via Apoptosis-Inducing.

机构信息

Pharmacy Department, the 967th Hospital of PLA Joint Logistics Support Force, Dalian, People's Republic of China.

Beijing Key Laboratory of Enze Biomass Fine Chemicals, Beijing Institute of Petrochemical Technology, Beijing, People's Republic of China.

出版信息

Drug Des Devel Ther. 2023 Feb 10;17:403-418. doi: 10.2147/DDDT.S387788. eCollection 2023.

DOI:10.2147/DDDT.S387788
PMID:36798807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9926987/
Abstract

PURPOSE

Current chemotherapy fails to offer a desirable efficacy in clinical treatment against breast cancer due to the extensive multi-drug resistance. In this study, we developed dual sensitization anti-resistant nanoparticles to treat refractory breast cancer, aiming to benefit from photodynamic therapy and chemotherapy.

METHODS

Hyaluronic acid (HA) derivative and photosensitizer chlorin e6 (Ce6) derivative were synthesized and confirmed by mass spectrometry. These derivatives and the chemotherapy agent paclitaxel were incorporated into nanoparticles by an emulsion-solvent evaporation method. The prepared nanoparticles were characterized by dynamic laser scattering, atomic force microscopy, and high performance liquid chromatography (HPLC). The efficacy and mechanisms of the nanoparticles, both in vitro and in vivo, were investigated by flow cytometry, confocal/fluorescence microscopy, and a high-content screening system.

RESULTS

The prepared dual sensitization anti-resistant nanoparticles were round with a diameter of ~ 100 nm, exhibiting high encapsulation efficiency for the anticancer agent paclitaxel. The nanoparticles demonstrated a robust inhibitory effect against drug-resistant breast cancer cells by enhanced uptake, synergistic effect of photodynamic therapy and chemotherapy, and apoptosis-inducing via multiple pathways. In vivo efficacy, biocompatibility and safety were further confirmed acceptable in tumor-bearing mice.

CONCLUSION

The prepared dual sensitization anti-resistant nanoparticles were promising to treat refractory breast cancer with a controllable treatment site and minimal side effects.

摘要

目的

由于广泛的多药耐药性，目前的化疗在乳腺癌的临床治疗中无法提供理想的疗效。在这项研究中，我们开发了双重增敏抗耐药纳米粒子来治疗难治性乳腺癌，旨在受益于光动力疗法和化学疗法。

方法

合成了透明质酸（HA）衍生物和光敏剂氯乙酮（Ce6）衍生物，并通过质谱法进行了确认。这些衍生物和化疗药物紫杉醇通过乳液溶剂蒸发法被包封到纳米粒子中。通过动态激光散射、原子力显微镜和高效液相色谱（HPLC）对制备的纳米粒子进行了表征。通过流式细胞术、共聚焦/荧光显微镜和高内涵筛选系统，在体外和体内研究了纳米粒子的功效和机制。

结果

所制备的双重增敏抗耐药纳米粒子呈圆形，直径约为 100nm，对抗癌药物紫杉醇具有高包封效率。纳米粒子通过增强摄取、光动力疗法和化学疗法的协同作用以及通过多种途径诱导细胞凋亡，对耐药乳腺癌细胞具有强大的抑制作用。在荷瘤小鼠中，进一步证实了其体内疗效、生物相容性和安全性可接受。

结论

所制备的双重增敏抗耐药纳米粒子有望用于治疗难治性乳腺癌，具有可控的治疗部位和最小的副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/f4ec957d0478/DDDT-17-403-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/200075764236/DDDT-17-403-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/7bbbbdb3a756/DDDT-17-403-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/35820a47df1f/DDDT-17-403-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/d0a0fb861d5e/DDDT-17-403-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/bdea8701f1c4/DDDT-17-403-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/48d4fc426d92/DDDT-17-403-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/116e8db8db7d/DDDT-17-403-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/f4ec957d0478/DDDT-17-403-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/200075764236/DDDT-17-403-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/7bbbbdb3a756/DDDT-17-403-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/35820a47df1f/DDDT-17-403-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/d0a0fb861d5e/DDDT-17-403-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/bdea8701f1c4/DDDT-17-403-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/48d4fc426d92/DDDT-17-403-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/116e8db8db7d/DDDT-17-403-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c13/9926987/f4ec957d0478/DDDT-17-403-g0008.jpg

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