Folic Acid-Modified Erythrocyte Membrane Loading Dual Drug for Targeted and Chemo-Photothermal Synergistic Cancer Therapy
| Autor: | Dahua He, Wanting Wang, Wanye Zhu, Ping Zhong, Yi Zhou, Yusheng Li, Qin Linghao, Huan Liu, Cui Wei, Pengfei Wang, Zhenpeng Huang, Zhihao Chen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Indocyanine Green
Drug Biodistribution media_common.quotation_subject Pharmaceutical Science Antineoplastic Agents Apoptosis 02 engineering and technology 030226 pharmacology & pharmacy Rats Sprague-Dawley Mice 03 medical and health sciences Drug Delivery Systems Folic Acid 0302 clinical medicine In vivo Cell Line Tumor Neoplasms Drug Discovery medicine Animals Humans Tissue Distribution Doxorubicin Dissolution testing media_common Cardiotoxicity Chemistry Erythrocyte Membrane Hep G2 Cells Hyperthermia Induced Phototherapy Photothermal therapy 021001 nanoscience & nanotechnology Combined Modality Therapy Rats Drug Liberation Cancer research Nanoparticles Molecular Medicine Nanocarriers 0210 nano-technology medicine.drug |
| Zdroj: | Molecular Pharmaceutics. 18:386-402 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.0c01008 |
| Popis: | To overcome the challenges of systemic toxicity and weak tumor selectivity caused by traditional antitumor drugs, numerous nanocarrier systems have been developed in recent decades, and their therapeutic effect has been improved to varying degrees. However, because of the drug resistance effect and metastasis involved in tumor recurrence, a single chemotherapy can no longer satisfy the diversified treatment needs. Recently, the application of chemotherapy in combination with thermotherapy as a synergistic approach has been proven to be more effective, and it provides a new strategy for cancer therapy. In this work, by utilizing the unique properties of erythrocytes, a surface-modified erythrocyte membrane was constructed as a novel nanocarrier system (DOX and ICG-PLGA@RBC nanoparticles, DIRNPs for short) for the simultaneous transportation of chemotherapeutic drugs (doxorubicin, DOX) and photothermal agents (indocyanine green, ICG) to achieve the effects of long-term circulation, active tumor targeting, and triggered drug release. The results indicated that DIRNPs have a nanoscale particle size of 158.4 nm with a narrow size distribution and a negative surface charge of -5.79 mV. No particle aggregation or remarkable drug leakage was observed during the 30 day storage test, and because of the excellent photothermal conversion ability of ICG, the local temperature of DIRNPs could dramatically increase from 33.7 to 49.8 °C in 10 min under near-infrared (NIR) laser irradiation. The in vitro drug dissolution data demonstrated that the DOX release from the DIRNPs was pH-dependent and NIR-triggered. Folic acid modifications of the erythrocyte membrane effectively facilitated the intracellular uptake of DIRNPs by HepG2 cells and, as a result, it significantly inhibited tumor cell growth, promoted reactive oxygen species levels, induced cell apoptosis, and restricted cell recovery and migration. In vivo pharmacokinetics and biodistribution studies indicated that the DIRNPs prolonged the half-life of DOX from 6.03 to 17.6 h and remarkably reduced the DOX level in the heart to avoid drug-related cardiotoxicity. More importantly, the DIRNPs exerted excellent in vivo antitumor efficacy against H22 tumors with superior safety. In conclusion, utilizing the advantageous properties of erythrocytes to construct a tumor-targeted biomimetic nanocarrier for codelivery of chemotherapeutics and photothermal agents to produce synergistic effects is considered an effective method for cancer therapy. |
| Databáze: | OpenAIRE |
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