Drug-Triggered Self-Assembly of Linear Polymer into Nanoparticles for Simultaneous Delivery of Hydrophobic and Hydrophilic Drugs in Breast Cancer Cells

Abstract

Breast cancer is the most devastating disease among females globally. Conventional chemotherapeutic regimen relies on the use of highly cytotoxic drugs as monotherapy and combination therapy leading to severe side effects to the patients as collateral damage. Moreover, combining hydrophobic and hydrophilic drugs create erratic biodistribution and suboptimal medicinal outcome. Hence, packaging multiple drugs of diverse mechanisms of action and biodistribution for safe delivery into tumor tissues with optimal dosages is indispensable for next-generation breast cancer therapy. To address these, in this report, we describe a unique cisplatin-triggered self-assembly of linear polymer into 3D-spherical sub 200 nm particles. These nanoparticles comprise a hydrophobic (paclitaxel) and hydrophilic drug (cisplatin) simultaneously in a single particle. Molecular dynamics simulation revealed hydrophilic–hydrophilic interaction and interchain H-bonding as underlying mechanisms of self-assembly. Confocal microscopy studies evidently demonstrated that these novel nanoparticles can home into lysosomes in breast cancer cells, fragment subcellular nuclei, and prevent cell division, leading to improved breast cancer cell death compared to free drug combination. Moreover, 3D-breast tumor spheroids were reduced remarkably by the treatment of these nanoparticles within 24 h. These dual-drug-loaded self-assembled polymeric nanoparticles have prospective to be translated into a clinical strategy for breast cancer patients.

A New Water-Soluble Thermosensitive Star-Like Copolymer as a Promising Carrier of the Chemotherapeutic Drug Doxorubicin

“…Linear polymers are mostly used for drug delivery to specific cells and tissues [8]. Recently provided studies, however, demonstrated the high efficiency of a branched copolymer of dextran-polyacrylamide, both as a nanocarrier for drug delivery and as a matrix for the preparation of new nanosystems for antitumor photodynamic therapy [9][10][11].…”

Targeted Delivery of Doxorubicin in HeLa Cells Using Self‐Assembled Polymeric Nanocarriers Guided by Deep Eutectic Solvents

“…[1][2][3] Synthetic biomaterials are often more suitable for such applications than natural biomaterials; [4][5][6] examples include modified carriers based on natural and synthetic polymers, metal complex, proteins, peptides, hydrogels, and ionic liquids (ILs); all of which exhibit considerable potential for cancer drug delivery system. [7][8][9][10][11][12] Ionic liquids (ILs) are beneficial for the development of sensors, electrochemistry, and in the development of catalysts and pharmaceuticals, and drug carriers. ILs drug carriers have been widely used in anticancer chemotherapy because of their excellent drug carrier and binding properties.…”

“…Such biomaterials are non‐toxic and increase thermal stability, drug encapsulation efficiency, biodegradability, biocompatibility, and a high degree of porosity for cell penetration [1–3] . Synthetic biomaterials are often more suitable for such applications than natural biomaterials; [4–6] examples include modified carriers based on natural and synthetic polymers, metal complex, proteins, peptides, hydrogels, and ionic liquids (ILs); all of which exhibit considerable potential for cancer drug delivery system [7–12] . Ionic liquids (ILs) are beneficial for the development of sensors, electrochemistry, and in the development of catalysts and pharmaceuticals, and drug carriers.…”

Natural deep eutectic solvent supported targeted solid–liquid polymer carrier for breast cancer therapy

“…1,2 There is an enormous attempt to explore the role/ function of synthetic biomaterials used in drug delivery applications. 3 Currently, synthetic and natural polymers, metal complexes, peptides, proteins, and hydrogels are used for the development of anticancer drug delivery systems, [4][5][6][7][8] which reduce some disadvantages over conventional anticancer treatments such as poor solubility, low biodegradability, toxic nature, and poor intracellular penetration, retention time and sustainable release of encapsulated drugs. 9 A signicant number of nanoparticles such as inorganic nanoparticles or other polymeric/liquid nanoparticles have also been used in developing drug carrier systems.…”