A Cationic Amphiphilic AIE Polymer for Mitochondrial Targeting and Imaging

Abstract

Mitochondria are important organelles that play key roles in generating the energy needed for life and in pathways such as apoptosis. Direct targeting of antitumor drugs, such as doxorubicin (DOX), to mitochondria into cells is an effective approach for cancer therapy and inducing cancer cell death. To achieve targeted and effective delivery of antitumor drugs to tumor cells, to enhance the therapeutic effect, and to reduce the side effects during the treatment, we prepared a cationic amphiphilic polymer with aggregation-induced emission (AIE) characteristic. The polymer could be localized to mitochondria with excellent organelle targeting, and it showed good mitochondrial targeting with low toxicity. The polymer could also self-assemble into doxorubicin-loaded micelles in phosphate buffer, with a particle size of about 4.3 nm, an encapsulation rate of 11.03%, and micelle drug loading that reached 0.49%. The results of in vitro cytotoxicity experiments showed that the optimal dosage was 2.0 μg/mL, which had better inhibitory effect on tumor cells and less biological toxicity on heathy cells. Therefore, the cationic amphiphilic polymer can partially replace expensive commercial mitochondrial targeting reagents, and it can be also used as a drug loading tool to directly target mitochondria in cells for corresponding therapeutic research.

Synthesis, Properties, and Biomedical Application of Dicationic Gemini Surfactants with Dodecane Spacer and Carbamate Fragments

“…The practice of incorporating cationic surfactants into the lipid bilayer of liposomes remains a relevant direction, as it allows for increasing the zeta potential of aggregates and, consequently, influencing their colloidal stability [35,59,96,97]. It has also been demonstrated that cationic components (including surfactants) have an affinity for cell membranes [98], organelles [99,100], and bacterial cell membranes [5]. In addition, cationic liposomes can utilize adsorptionmediated transcytosis, which is widely recognized as the main BBB entry mechanism for cationic proteins and nanocarriers [48,63,101,102].…”

Aggregation-Induced Emission Luminogen-Encapsulated Fluorescent Hydrogels Enable Rapid and Sensitive Quantitative Detection of Mercury Ions

“…Oppositely, AIEgens proposed by Tang’s group [ 26 ] in 2001 exhibit significantly enhanced fluorescence under aggregation state, which fundamentally overcomes the deficiency of the ACQ effect [ 27 , 28 ]. Since then, AIEgens have been widely used in fields of biochemical sensors [ 29 , 30 , 31 ], bioimaging [ 32 , 33 , 34 , 35 ] and nanomedicine [ 36 , 37 ]. However, in AIE-based chemosensors, the majority of hydrophobic AIEgens disperse in an aggregation state in aqueous solution, which largely restricts the reaction efficiency of AIEgens with hydrosoluble targets, such as ions [ 38 ].…”

The Nanostructured Self-Assembly and Thermoresponsiveness in Water of Amphiphilic Copolymers Carrying Oligoethylene Glycol and Polysiloxane Side Chains

“…In particular, amphiphilic polymeric nanostructure can be exploited as a platform, that can be also functionalized with targeting moieties, in the design of carriers for various payloads, such as nucleic acids, small molecules and proteins, to aid their therapeutic effect and limit their adverse impact ideally targeting specific organs, tissues, or cells [ 30 ]. To be effective in such a complex environment, stimuli-responsive self-assembled nanostructures are particularly appealing for biomedical applications such as imaging probes and drug delivery systems susceptible to different triggers, i.e., pH [ 31 ], ionic strength [ 32 ], polarity [ 15 , 33 , 34 ], local viscosity and aggregation state [ 35 , 36 , 37 ], light [ 9 ], redox potential [ 38 , 39 ], and temperature [ 4 , 40 , 41 , 42 ]. Moreover, the effect of the size of the carriers is one of the more intuitive parameters to be taken into account in the development of more effective carriers.…”