Green surfactant-dendrimer aggreplexes: An ingenious way to launch dual attack on arch-enemy cancer

Nilesh Malavia; Rohan Ghadi; Kaushik Kuche; Tushar Date; Nallamothu Bhargavi; Dasharath Chaudhari; Rajan Swami; Parmeshwar B Katare; Sanjay K Banerjee; Sanyog Jain

doi:10.1016/j.colsurfb.2021.111821

Green surfactant-dendrimer aggreplexes: An ingenious way to launch dual attack on arch-enemy cancer

Colloids Surf B Biointerfaces. 2021 Aug:204:111821. doi: 10.1016/j.colsurfb.2021.111821. Epub 2021 May 5.

Affiliations

¹ Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, 160062, Punjab, India.
² Drug Discovery Research Centre, Translational Health Science and Technology Institute, Faridabad, 121001, India.
³ Drug Discovery Research Centre, Translational Health Science and Technology Institute, Faridabad, 121001, India; Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781101, India.
⁴ Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, 160062, Punjab, India. Electronic address: sanyogjain@niper.ac.in.

PMID: 33971612
DOI: 10.1016/j.colsurfb.2021.111821

Abstract

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.

Keywords: Aggreplexes; Dendrimer; Docetaxel; Green surfactant; shRNA.

MeSH terms

Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Cell Line, Tumor
Dendrimers*
Docetaxel
Drug Carriers
Nanoparticles*
Neoplasms* / drug therapy
Neoplasms* / genetics
Particle Size
Surface-Active Agents

Substances

Antineoplastic Agents
Dendrimers
Drug Carriers
Surface-Active Agents
Docetaxel