Green surfactant-dendrimer aggreplexes: An ingenious way to launch dual attack on arch-enemy cancer
| Autor: | Rohan Ghadi, Rajan Swami, Tushar Date, Sanyog Jain, Parmeshwar B. Katare, Dasharath Chaudhari, Kaushik Kuche, Nallamothu Bhargavi, Nilesh Malavia, Sanjay K. Banerjee |
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| Rok vydání: | 2020 |
| Předmět: |
Dendrimers
Amidoamine Antineoplastic Agents 02 engineering and technology Docetaxel 01 natural sciences Small hairpin RNA chemistry.chemical_compound Surface-Active Agents Colloid and Surface Chemistry Pulmonary surfactant Dendrimer Cell Line Tumor Neoplasms 0103 physical sciences Physical and Theoretical Chemistry Particle Size Cytotoxicity Carbodiimide Drug Carriers 010304 chemical physics Oligonucleotide Surfaces and Interfaces General Medicine Transfection 021001 nanoscience & nanotechnology chemistry Biophysics Nanoparticles 0210 nano-technology Biotechnology |
| Zdroj: | Colloids and surfaces. B, Biointerfaces. 204 |
| ISSN: | 1873-4367 |
| Popis: | Combination therapy, which combines anti-cancer drugs with different oligonucleotides, have shown potential in cancer treatment. However, delivering a hydrophobic anti-cancer drug and a hydrophilic oligonucleotide simultaneously is a herculean task. This study takes advantage of interactions between histidine-lauric acid-based green surfactant and poly(amidoamine) dendrimers to achieve this aim. The green surfactant was synthesized by carbodiimide chemistry and characterized by FTIR, 1H-NMR, and mass spectroscopy. Further, green surfactant-dendrimer aggregates encapsulating DTX and complexing SIRT 1 shRNA i.e., “aggreplexes” were developed and characterized. The term “aggreplexes” signifies complexes which are formed between green-surfactant-dendrimer aggregates and SIRT-1 shRNA via electrostatic interaction. The aggreplexes displayed particle size of 262.33 ± 3.87 nm, PDI of 0.25 and entrapment efficiency of 70.56 %. The TEM images revealed spherical shape of aggreplexes with irregular outer surface and corroborated particle size obtained from zetasizer. The in-vitro release study revealed biphasic release patterns of DTX from aggreplexes and were compatible for intravenous administration. Further, aggreplexes augmented cellular uptake in MDA-MB-231 cells by ∼1.87-fold compared to free DTX. Also, EGFP expression revealed significantly higher transfection of aggreplexes compared to naked shRNA and Superfect™ complexes. Further, aggreplexes showed higher cytotoxicity in MDA-MB-231 cells and ∼4.16-fold reduction in IC50 value compared to free DTX. Finally, apoptosis-index observed in case of aggreplexes was ∼3.57-fold higher than free DTX. These novel aggreplexes showed increased drug loading capacity and superior gene transfection potential. Thus, they open new avenues for co-delivery of hydrophobic anti-cancer drugs and hydrophilic therapeutic genes for improving current standards of cancer therapy. |
| Databáze: | OpenAIRE |
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